bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes Associated With Preoperative Use of Extracorporeal Membrane Oxygenation in Children Undergoing Heart Operation for Congenital Heart Disease: A Multi‐institutional Analysis
Authors: Gupta Punkaj , Robertson Michael J. , Beam Brandon W. , Rettiganti Mallikarjuna
Published: December 2014

Background

There are
very sparse data on patient outcomes related to the use of extracorporeal membrane oxygenation (ECMO) prior to heart operation in children with congenital heart disease. This study was designed to evaluate this association using the Pediatric Health Information System (PHIS) database.

Hypothesis

We hypothesize that patients receiving ECMO prior to heart operation will have worse outcomes, including mortality, compared with patients receiving ECMO after heart operation.

Methods

Patients age ≤18 years receiving ECMO before or after pediatric heart operation (with or without cardiopulmonary bypass) at a PHIS‐participating hospital from 2004 to 2013 were included. Multivariable logistic regression or Cox proportional‐hazards models were fitted to study the effect of timing of ECMO initiation in relation to cardiac surgery on study outcomes.

Results

A total of 3498 patients from 42 hospitals qualified for inclusion. Of these, 494 (14%) received ECMO prior to heart operation (presurgery ECMO) and 3004 (86%) received ECMO after heart operation (postsurgery ECMO). Unadjusted mortality was significantly lower in the presurgery ECMO group compared with the postsurgery ECMO group (30% vs 45%; P < 0.0001). After adjusting for patient and center characteristics, odds of mortality were significantly lower in the presurgery ECMO group (odds ratio: 0.46, 95% confidence interval: 0.36‐0.59, P < 0.0001). There were no significant differences in ECMO duration, length of hospital stay, and hospital charges between the 2 groups in adjusted models.

Conclusions

This study suggests that ECMO can be used with satisfactory outcomes prior to heart operation in children with congenital heart disease.
Stereological study of pyramidal neurons in the human superior temporal gyrus from childhood to adulthood
Authors: Barger Nicole , Sheley Matthew F. , Schumann Cynthia M.
Published: December 2014

The association cortex of the superior temporal gyrus (STG) is implicated in complex social and linguistic functions. Thus, reliable methods for quantifying cellular variation in this region could greatly benefit researchers interested in addressing the cellular correlates of typical and atypical function associated with these critical cognitive abilities. To facilitate this task, we first present a general set of cytoarchitectonic criteria targeted specifically toward stereological analyses of thick, Nissl‐stained sections for the homotypical cortex of the STG, referred to here as BA22/TA. Second, we use the optical fractionator to estimate pyramidal neuron number and the nucleator for pyramidal somal and nuclear volume. We also investigated the influence of age and sex on these parameters, as well as set a typically developing baseline for future comparisons.

In 11 typically developing cases aged 4–48 years, the most distinguishing features of BA22/TA were the presence of distinct granular layers, a prominent, jagged layer IIIc, and a distinctly staining VIa. The average number of neurons was 91 ± 15 million, the volume of pyramidal soma 1,512 µm3, and the nuclear volume 348 µm3. We found no correlation with age and neuron number. In contrast, pyramidal somal and nuclear volume were both negatively correlated and linearly associated with age in regression analyses. We found no significant sex differences. Overall, the data support the idea that postnatal neuron numbers are relatively stable through development but also suggest that neuronal volume may be subject to important developmental variation. Both measures are critical variables in the study of developmental neuropathology. J. Comp. Neurol. 523:1054–1072, 2015. © 2015 Wiley Periodicals, Inc.
Differential coexpression of FoxP1, FoxP2, and FoxP4 in the Zebra Finch (Taeniopygia guttata) song system
Authors: Mendoza Ezequiel , Tokarev Kirill , Düring Daniel N. , Retamosa Eva Camarillo , Weiss Michael , Arpenik Nshdejan , Scharff Constance
Published: December 2014

Heterozygous disruptions of the Forkhead transcription factor FoxP2 impair acquisition of speech and language. Experimental downregulation in brain region Area X of the avian ortholog FoxP2 disrupts song learning in juvenile male zebra finches. In vitro, transcriptional activity of FoxP2 requires dimerization with itself or with paralogs FoxP1 and FoxP4. Whether this is the case in vivo is unknown. To provide the means for future functional studies we cloned FoxP4 from zebra finches and compared regional and cellular coexpression of FoxP1, FoxP2, and FoxP4 mRNA and protein in brains of juvenile and adult male zebra finches. In the telencephalic song nuclei HVC, RA, and Area X, the three investigated FoxPs were either expressed alone or occurred in specific combinations with each other, as shown by double in situ hybridization and triple immunohistochemistry. FoxP1 and FoxP4 but not FoxP2 were expressed in RA and in the HVCRA and HVCX projection neurons. In Area X and the surrounding striatum the density of neurons expressing all three FoxPs together or FoxP1 and FoxP4 together was significantly higher than the density of neurons expressing other combinations. Interestingly, the proportions of Area X neurons expressing particular combinations of FoxPs remained constant at all ages. In addition, FoxP‐expressing neurons in adult Area X express dopamine receptors 1A, 1B, and 2. Together, these data provide the first evidence that Area X neurons can coexpress all avian FoxP subfamily members, thus allowing for a variety of regulatory possibilities via heterodimerization that could impact song behavior in zebra finches. J. Comp. Neurol. 523:1318–1340, 2015. © 2014 Wiley Periodicals, Inc.
Q Curvature on a Class of 3‐Manifolds
Authors: Hang Fengbo , Yang Paul C.
Published: December 2014

Motivated by the strong maximum principle for the Paneitz operator in dimension 5 or higher found in a preprint by Gursky and Malchiodi and the calculation of the second variation of the Green's function pole's value on 𝕊3 in our preprint, we study the Riemannian metric on 3‐manifolds with positive scalar and Q curvature. Among other things, we show it is always possible to find a constant Q curvature metric in the conformal class. Moreover, the Green's function is always negative away from the pole, and the pole's value vanishes if and only if the Riemannian manifold is conformal diffeomorphic to the standard 𝕊3. Compactness of constant Q curvature metrics in a conformal class and the associated Sobolev inequality are also discussed. © 2016 Wiley Periodicals, Inc.
Identification of a major metabolite of danshensu in rat urine and simultaneous determination of danshensu and its metabolite in plasma: application to a pharmacokinetic study in rats
Authors: Wang Xiangyang , Li Wei , Ma Xiaohui , Yan Kaijing , Chu Yang , Han Min , Li Shuming , Zhang Hongchao , Zhou Shuiping , Zhu Yonghong , Sun He , Liu Changxiao
Published: December 2014

Danshensu, as the effective component of Salvia miltiorrhiza (Danshen), has been widely used in clinical studies for treatment of cardiovascular diseases in China. A new metabolite, 4‐hydroxy‐3‐methoxyphenyllactic acid was isolated from the urine of rats, and its chemical structure was identified by ultraviolet (UV), Infrared Spectroscopy (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR). Furthermore, a selective and sensitive high performance liquid chromatography‐tandem mass spectrometric (HPLC‐MS/MS) method was developed for the simultaneous quantification of danshensu and its major metabolite, 4‐hydroxy‐3‐methoxyphenyllactic acid, in rat plasma after oral and intravenous administration of danshensu. The separation was performed on a Hypersil Gold C18 column (150 × 2.1 mm i.d., 3.0 µm, Thermo, San jose CA, USA) with gradient elution using a mobile phase composed of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. Linear detection responses were obtained for danshensu and 4‐hydroxy‐3‐methoxyphenyllactic acid ranging from 5 to 10000 ng/mL and 5 to 4000 ng/mL, respectively. The lower limits of quantification (LLOQs) for the two compounds were both 5 ng/mL. The intra‐and inter‐day precision (R.S.D %) were within 5.61% for the two analytes. The average recoveries of the analytes were greater than 72.43%. The method was proved to be stable during all sample storage, preparation and analytic procedures. This method was successfully applied to the pharmacokinetic studies of danshensu and 4‐hydroxy‐3‐methoxyphenyllactic acid after oral and intravenous administration of danshensu in rats.Copyright © 2014 John Wiley & Sons, Ltd.
Follow‐up mortality study of compulsorily treated patients with anorexia nervosa
Authors: Ward Anne , Ramsay Rosalind , Russell Gerald , Treasure Janet
Published: December 2014

Objective

In a previous study we found that compulsory inpatient treatment was associated with an increase in the number of deaths over the following 5 years when compared to non‐compulsory admission. This study aimed to examine the longer term mortality of patients admitted compulsorily.

Method

The mortality outcome of patients with a compulsory admission (n = 81) and a comparison group (n = 81) of patients admitted to the specialized eating disorder unit at the Maudsley Hospital in the period 1983‐95 was traced over two decades through the National Register held by the National Health Service (NHS) Central Register.

Results

Approximately 20 years following admission there were 27 deaths in the series. The standardized mortality rate in the compulsory treatment group no longer differed significantly from that of the non‐compulsory group. The suicides were not particularly linked with compulsory admission.

Discussion

Although the mortality in the 5 years following a compulsory admission is higher than that seen in the non‐compulsory patients, this difference is attenuated over time. The overall standardized mortality rate remains elevated. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:860–865)
Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure
Authors: Miller Wayne L. , Borgeson Daniel D. , Grantham J. Aaron , Luchner Andreas , Redfield Margaret M. , Burnett John C.
Published: December 2014

Aims

Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF.

Methods and results

Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38‐day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression.

Conclusions

Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.
Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL‐10
Authors: Tao Huimin , Lu Lin , Xia Yang , Dai Fu , Wang Yi , Bao Yangyi , Lundy Steven K. , Ito Fumito , Pan Qin , Zhang Xiaolian , Zheng Fang , Shu Guoshun , Fang Bingmu , Jiang Jinhong , Xia Jianchuang , Huang Shiang , Li Qiao , Chang Alfred E.
Published: December 2014

We have previously reported that adoptive transfer of tumor‐draining lymph node (TDLN) B cells confers tumor regression in a spontaneous pulmonary metastasis mouse model of breast cancer. In this study, we identified IL‐10‐producing cells within these B cells, and found that IL‐10 removal, either by using IL‐10−/− TDLN B cells or by systemic neutralization of IL‐10, significantly augmented the therapeutic efficacy of adoptively transferred TDLN B cells. Depletion of IL‐10 in B‐cell adoptive transfers significantly increased CTLs and B‐cell activity of PBMCs and splenic cells in the recipient. Activated TDLN B cells express Fas ligand, which was further enhanced by coculture of these TDLN B cells with 4T1 tumor cells. Effector B cells killed tumor cells directly in vitro in an antigen specific and Fas ligand‐dependent manner. Trafficking of TDLN B cells in vivo suggested that they were recruited to the tumor and lung as well as secondary lymphoid organs. These findings further define the biological function of antitumor effector B cells, which may offer alternative cellular therapies to cancer.
Monocyte‐derived dendritic cells can induce autoreactive CD4+ T cells showing myeloid lineage directed reactivity in healthy individuals
Authors: Lam Tin Sing , van de Meent Marian , Falkenburg JH Frederik , Jedema Inge
Published: December 2014

T cells against self‐antigens can be detected in peripheral blood of healthy individuals, although intrathymic negative selection removes most high‐avidity T cells specific for self‐antigens from the peripheral repertoire. Moreover, spontaneous T‐cell proliferation following stimulation with autologous monocyte‐derived dendritic cells (autoDCs) has been observed in vitro. In this study, we characterized the nature and immunological basis of the autoDC reactivity in the T‐cell repertoire of healthy donors. We show that a minority of naive and memory CD4+ T cells within the healthy human T‐cell repertoire mediates HLA‐restricted reactivity against autoDCs, which behave like a normal antigen‐specific immune response. This reactivity appeared to be primarily directed against myeloid lineage cells. Although cytokine production by the reactive T cells was observed, this did not coincide with overt cytotoxic activity against autoDCs. AutoDC reactivity was also observed in the CD8+ T‐cell compartment, but this appeared to be mainly cytokine‐induced rather than antigen‐driven. In conclusion, we show that the presence of autoreactive T cells harboring the potential to react against autologous and HLA‐matched allogeneic myeloid cells is a common phenomenon in healthy individuals. These autoDC‐reactive T cells may help the induction of primary T‐cell responses at the DC priming site.
Protective effect of a germline, IL‐17‐neutralizing antibody in murine models of autoimmune inflammatory disease
Authors: Dallenbach Kiran , Maurer Patrik , Röhn Till , Zabel Franziska , Kopf Manfred , Bachmann Martin F.
Published: December 2014

Monoclonal antibodies (mAbs) inhibiting cytokines have recently emerged as new drug modalities for the treatment of chronic inflammatory diseases. Interleukin‐17 (IL‐17) is a T‐cell‐derived central mediator of autoimmunity. Immunization with Qβ‐IL‐17, a virus‐like particle based vaccine, has been shown to produce autoantibodies in mice and was effective in ameliorating disease symptoms in animal models of autoimmunity. To characterize autoantibodies induced by vaccination at the molecular level, we generated mouse mAbs specific for IL‐17 and compared them to germline Ig sequences. The variable regions of a selected hypermutated high‐affinity anti‐IL‐17 antibody differed in only three amino acid residues compared to the likely germline progenitor. An antibody, which was backmutated to germline, maintained a surprisingly high affinity (0.5 nM). The ability of the parental hypermutated antibody and the derived germline antibody to block inflammation was subsequently tested in murine models of multiple sclerosis (experimental autoimmune encephalomyelitis), arthritis (collagen‐induced arthritis), and psoriasis (imiquimod‐induced skin inflammation). Both antibodies were able to delay disease onset and significantly reduced disease severity. Thus, the mouse genome unexpectedly encodes for antibodies with the ability to functionally neutralize IL‐17 in vivo.
A Ca2+ concentration of 1.5 mM, as present in IMDM but not in RPMI, is critical for maximal response of Th cells to PMA/ionomycin
Authors: Zimmermann Jakob , Radbruch Andreas , Chang Hyun‐Dong
Published: December 2014

Restimulation of memory–effector T helper lymphocytes with PMA/ionomycin is an established technique to determine their imprinting for the expression of cytokine genes, that is their functional potential. Here, we show that for the maximal reexpression of cytokine genes, the Ca2+ concentration of the medium has to be greater than 1.5 mM. For RPMI (Roswell Park Memorial Institute 1640), the most commonly used medium, the Ca2+ concentration has to be increased from the regular 0.42 to 1.5 mM.
Development of a microfluidic‐based assay on a novel nitrocellulose platform
Authors: Arrastia Mary , Avoundjian Ani , Ehrlich Paul Said , Eropkin Micah , Levine Leanna , Gomez Frank A.
Published: December 2014

A novel microfluidic paper‐based analytical device (μPAD) utilizing a nitrocellulose (NC) membrane to detect IgG antibodies through a colorimetric analysis is described. The μPAD was constructed using layered polyethylene terephthalate (PET) and pressure‐sensitive adhesives (PSA). The biotin labeled Goat Anti‐Mouse IgG antibody was spotted and dried on the NC channel prior to subjecting it to a series of wash solutions (Tris‐tween), increasing concentrations of alkaline phosphatase conjugated to streptavidin (Strep‐ALP), and para‐nitrophenyl phosphate (p‐NPP) realizing a vibrant yellow color. The reaction proceeds for 10 min before applying the p‐NPP stop solution. The device was then dried, scanned, and analyzed yielding a linear range of inverse yellow color intensities versus Strep‐ALP concentrations. The development of this simple μPAD should further facilitate the use of NC in colorimetric assays to detect and quantitate antibodies.
A versatile electrophoresis‐based self‐test platform
Authors: Staal Steven , Ungerer Mathijn , Floris Arjan , Ten Brinke Hans‐Willem , Helmhout Roy , Tellegen Marian , Janssen Kjeld , Karstens Erik , van Arragon Charlotte , Lenk Stefan , Staijen Erik , Bartholomew Jody , Krabbe Hans , Movig Kris , Dubský Pavel , van den Berg Albert , Eijkel Jan
Published: December 2014

This paper reports on recent research creating a family of electrophoresis‐based point of care devices for the determination of a wide range of ionic analytes in various sample matrices. These devices are based on a first version for the point‐of‐care measurement of Li+, reported in 2010 by Floris et al. (Lab Chip 2010, 10, 1799–1806). With respect to this device, significant improvements in accuracy, precision, detection limit, and reliability have been obtained especially by the use of multiple injections of one sample on a single chip and integrated data analysis. Internal and external validation by clinical laboratories for the determination of analytes in real patients by a self‐test is reported. For Li+ in blood better precision than the standard clinical determination for Li+ was achieved. For Na+ in human urine the method was found to be within the clinical acceptability limits. In a veterinary application, Ca2+ and Mg2+ were determined in bovine blood by means of the same chip, but using a different platform. Finally, promising preliminary results are reported with the Medimate platform for the determination of creatinine in whole blood and quantification of both cations and anions through replicate measurements on the same sample with the same chip.
The Catalytic Performance of Metalloporphyrins during Hydrogenation of Anthracene
Authors: Liu He , Ji Shunfeng , Wang Zongxian , Guo Aijun , Chen Kun
Published: December 2014

The potential catalytic performance of metalloporphyrins (MPs) for the hydrogenation of anthracene was investigated. The hydrogenation of anthracene with MPs, sulfur, or a combination of both was investigated. The MPs showed a small amount of catalytic activity for the hydrogenation reaction. Sulfur markedly improved the catalytic activity of the MPs. To probe demetalation of the MPs and the formation of catalytic species, conversions of the MPs were evaluated by UV/Vis spectroscopy. The solids formed in situ with α‐Al2O3 as a carrier during the hydrogenation with nickel tetraphenylporphyrin and sulfur were characterized by Raman, X‐ray photoelectron (XPS), and energy‐dispersive X‐ray spectroscopy (EDS). In the presence of sulfur, high conversions of the MPs were obtained. Raman spectroscopy, XPS, and EDS analyses suggested that the catalytic species were mixtures of different nickel sulfide phases with NiS as the main component. Thus, with the aid of sulfur, the MPs could be readily demetalated and then sulfided to catalytic species, and thus it is possible to activate inherent MPs to improve the hydroconversion of heavy oil.
Use of an exposure chamber to maintain aqueous phase nanoparticle dispersions for improved toxicity testing in fish
Authors: Boyle David , Boran Halis , Atfield Andrew J. , Henry Theodore B.
Published: December 2014

A novel chamber for maintaining aqueous phase dispersions of nanoparticles (NPs) to enable improved toxicity testing in larval zebrafish was developed. Aqueous concentrations were within 80% of initial NP concentrations, and the 96-h median lethal concentration (LC50) values were highly reproducible (coefficient of variation <0.16, n = 3 tests). Significantly lower toxicity for each NP tested (Ag, Cu, and TiO2NPs) in static beakers suggested that traditional acute toxicity tests may underestimate aqueous phase toxicity of NPs. Environ Toxicol Chem 2015;34:583–588. © 2014 SETAC
Sublethal effects of aged oil sands–affected water on white sucker (Catostomus commersonii)
Authors: Arens Collin J. , Hogan Natacha S. , Kavanagh Richard J. , Mercer Angella G. , Kraak Glen J. Van Der , van den Heuvel Michael R.
Published: December 2014

To investigate impacts of proposed oil sands aquatic reclamation techniques on benthic fish, white sucker (Catostomus commersonii Lacépède, 1803) were stocked in 2 experimental ponds—Demonstration Pond, containing aged fine tailings capped with fresh water, consistent with proposed end-pit lake designs, and South Bison Pond, containing aged unextracted oil sands material—to examine the effects of unmodified hydrocarbons. White sucker were stocked from a nearby reservoir at both sites in May 2010 and sampled 4 mo later to measure indicators of energy storage and utilization. Comparisons were then made with the source population and 2 reference lakes in the region. After exposure to aged tailings, white sucker had smaller testes and ovaries and reduced growth compared with the source population. Fish introduced to aged unextracted oil sands material showed an increase in growth over the same period. Limited available energy, endocrine disruption, and chronic stress likely contributed to the effects observed, corresponding to elevated concentrations of naphthenic acids, aromatic compounds in bile, and increased CYP1A activity. Because of the chemical and biological complexity of these systems, direct cause–effect relationships could not be identified; however, effects were associated with naphthenic acids, polycyclic aromatic hydrocarbons, ammonia, and high pH. Impacts on growth have not been previously observed in pelagic fishes examined in these systems, and may be related to differences in sediment interaction. Environ Toxicol Chem 2015;34:589–599. © 2014 SETAC
Toxicity of sediments from lead–zinc mining areas to juvenile freshwater mussels (Lampsilis siliquoidea) compared to standard test organisms
Authors: Besser John M. , Ingersoll Christopher G. , Brumbaugh William G. , Kemble Nile E. , May Thomas W. , Wang Ning , MacDonald Donald D. , Roberts Andrew D.
Published: December 2014

Sediment toxicity tests compared chronic effects on survival, growth, and biomass of juvenile freshwater mussels (28-d exposures with Lampsilis siliquoidea) to the responses of standard test organisms—amphipods (28-d exposures with Hyalella azteca) and midges (10-d exposures with Chironomus dilutus)—in sediments from 2 lead–zinc mining areas: the Tri-State Mining District and Southeast Missouri Mining District. Mussel tests were conducted in sediments sieved to <0.25 mm to facilitate recovery of juvenile mussels (2–4 mo old). Sediments were contaminated primarily with lead, zinc, and cadmium, with greater zinc and cadmium concentrations in Tri-State sediments and greater lead concentrations in southeast Missouri sediments. The frequency of highly toxic responses (reduced 10% or more relative to reference sites) in Tri-State sediments was greatest for amphipod survival (25% of samples), midge biomass (20%), and mussel survival (14%). In southeast Missouri sediments, the frequency of highly toxic samples was greatest for mussel biomass (25%) and amphipod biomass (13%). Thresholds for metal toxicity to mussels, expressed as hazard quotients based on probable effect concentrations, were lower for southeast Missouri sediments than for Tri-State sediments. Southeast Missouri sites with toxic sediments had 2 or fewer live mussel taxa in a concurrent mussel population survey, compared with 7 to 26 taxa at reference sites. These results demonstrate that sediment toxicity tests with juvenile mussels can be conducted reliably by modifying existing standard methods; that the sensitivity of mussels to metals can be similar to or greater than standard test organisms; and that responses of mussels in laboratory toxicity tests are consistent with effects on wild mussel populations. Environ Toxicol Chem 2015;34:626–639. © 2014 SETAC
Effects of pyrethroid insecticides in urban runoff on Chinook salmon, steelhead trout, and their invertebrate prey
Authors: Weston Donald P. , Schlenk Daniel , Riar Navneet , Lydy Michael J. , Brooks Marjorie L.
Published: December 2014

Pyrethroid insecticides can affect salmonids either indirectly through toxicity to their prey or directly by toxicity to the fish themselves. In support of a study on pyrethroid impacts to Chinook salmon and steelhead trout in the American River (Sacramento, California, USA), 96-h median effective concentration (EC50) and median lethal concentration (LC50) values for the pyrethroid bifenthrin were determined for taxa not traditionally used for toxicity testing but of interest as salmonid prey, including a chironomid, caddisflies, mayflies, and stoneflies. A laboratory was constructed on the banks of the American River to expose macroinvertebrates, Chinook salmon, and steelhead trout to flow-through river water containing urban runoff during storm events. Bifenthrin from urban runoff was found in river water following 5 rain events, reaching 14.6 ng/L. Mortality to the exposed salmonids was not observed, and sublethal effects were not seen in vitellogenin or sex steroid levels. Indirect effects via toxicity to salmonid prey are possible. Mortality to Hyalella azteca, a potential prey, was observed in every event tested, and peak bifenthrin concentrations were comparable to the 96-h EC50 of the caddisfly, Hydropsyche sp., the most important prey species on a biomass basis for American River Chinook salmon. The other invertebrates tested had EC50s exceeding bifenthrin concentrations seen in the American River, though could potentially be at risk at concentrations previously reported in smaller urban tributaries. Environ Toxicol Chem 2015;34:649–657. © 2014 SETAC
Influence of carbon nanotubes on the bioavailability of fluoranthene
Authors: Linard Erica N. , van den Hurk Peter , Karanfil Tanju , Apul Onur G. , Klaine Stephen J.
Published: December 2014

Concurrent with the increase in the use of carbon nanotubes (CNTs) in society is the rise of their introduction into the environment. Carbon nanotubes cause adverse effects themselves, and they have the potential to adsorb contaminants such as polycyclic aromatic hydrocarbons (PAHs). Although CNTs have a high adsorption capacity for PAHs and these contaminants can co-occur in the environment, few studies have characterized the bioavailability of CNT-adsorbed PAHs to fish. The goal of the present study was to characterize the bioavailability of fluoranthene adsorbed to suspended multiwalled-carbon nanotubes (MWNTs) in freshwater containing natural organic matter (NOM). Adsorption isotherms indicated that NOM influenced the adsorption of fluoranthene to MWNTs, although in the absence of MWNTs it did not influence the bioavailability of fluoranthene to Pimephales promelas. Pimephales promelas were exposed for 16 h in synthetic moderately hard water containing fluoranthene in the presence of different concentrations of NOM, and fluoranthene adsorbed to MWNTs in the presence of NOM. Bioavailable fluoranthene was quantified in each exposure through bile analysis using fluorescence spectrophotometry. By comparing the concentration of fluoranthene metabolites in the bile with the concentration of fluoranthene added to MWNT and NOM solutions, the relative bioavailability of fluoranthene adsorbed to MWNTs was quantified. Results indicate that approximately 60% to 90% of the fluoranthene was adsorbed to the MWNTs and that adsorbed fluoranthene was not bioavailable to P. promelas. The results also suggest that fluoranthene is not desorbed from ingested MWNT, and the bioavailable fraction is only the freely dissolved fluoranthene in the aqueous phase. Environ Toxicol Chem 2015;34:658–666. © 2014 SETAC
Quantitative multigene FISH on breast carcinomas identifies der(1;16)(q10;p10) as an early event in luminal A tumors
Authors: Rye Inga H. , Lundin Pär , Månér Susanne , Fjelldal Renathe , Naume Bjørn , Wigler Michael , Hicks James , Børresen‐Dale Anne‐Lise , Zetterberg Anders , Russnes Hege G.
Published: December 2014

In situ detection of genomic alterations in cancer provides information at the single cell level, making it possible to investigate genomic changes in cells in a tissue context. Such topological information is important when studying intratumor heterogeneity as well as alterations related to different steps in tumor progression. We developed a quantitative multigene fluorescence in situ hybridization (QM FISH) method to detect multiple genomic regions in single cells in complex tissues. As a “proof of principle” we applied the method to breast cancer samples to identify partners in whole arm (WA) translocations. WA gain of chromosome arm 1q and loss of chromosome arm 16q are among the most frequent genomic events in breast cancer. By designing five specific FISH probes based on breakpoint information from comparative genomic hybridization array (aCGH) profiles, we visualized chromosomal translocations in clinical samples at the single cell level. By analyzing aCGH data from 295 patients with breast carcinoma with known molecular subtype, we found concurrent WA gain of 1q and loss of 16q to be more frequent in luminal A tumors compared to other molecular subtypes. QM FISH applied to a subset of samples (n = 26) identified a derivative chromosome der(1;16)(q10;p10), a result of a centromere‐close translocation between chromosome arms 1q and 16p. In addition, we observed that the distribution of cells with the translocation varied from sample to sample, some had a homogenous cell population while others displayed intratumor heterogeneity with cell‐to‐cell variation. Finally, for one tumor with both preinvasive and invasive components, the fraction of cells with translocation was lower and more heterogeneous in the preinvasive tumor cells compared to the cells in the invasive component. © 2014 The Authors Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.
Ankle‐brachial index and inter‐artery blood pressure differences as predictors of cognitive function in overweight and obese older adults with diabetes: results from the Action for Health in Diabetes movement and memory study
Authors: Espeland Mark A. , Beavers Kristen M. , Gibbs Bethany Barone , Johnson Karen C. , Hughes Timothy M. , Baker Laura D. , Jakicic John , Korytkowski Mary , Miller Marsha , Bray George A.
Published: December 2014

Objective

Ankle‐brachial index (ABI) and interartery systolic blood pressure differences, as markers of vascular disease, are plausible risk factors for deficits in cognitive function among overweight and obese adults with type 2 diabetes.

Methods

The ABI and maximum interartery differences (MIAD) in systolic blood pressures were assessed annually for five years among 479 participants assigned to the control condition in a randomized clinical trial of a behavioral weight loss intervention. A battery of standardized cognitive function tests was administered 4 to 5 years later. Analyses of covariance were used to assess relationships that ABI, MIAD, and progression of ABI and MIAD had with cognitive function.

Results

There was a curvilinear relationship between ABI and a composite index of cognitive function (p = 0.03), with lower ABI being associated with poorer function. In graded fashions, both greater MIAD and increases in MIAD over time also had modest relationships with poorer verbal memory (both p ≤ 0.05), processing speed (both p ≤ 0.05), and composite cognitive function (both p < 0.04). These relationships were independent of each other and remained evident after extensive covariate adjustment.

Conclusions

In overweight and obese adults with type 2 diabetes, lower ABI and larger interartery systolic blood pressure differences have modest, independent, graded relationships with poorer cognitive function 4–5 years later. Copyright © 2014 John Wiley & Sons, Ltd.
Personal experience with narrated events modulates functional connectivity within visual and motor systems during story comprehension
Authors: Chow Ho Ming , Mar Raymond A. , Xu Yisheng , Liu Siyuan , Wagage Suraji , Braun Allen R.
Published: December 2014

Past experience of everyday life activities, which forms the basis of our knowledge about the world, greatly affects how we understand stories. Yet, little is known about how this influence is instantiated in the human brain. Here, we used functional magnetic resonance imaging to investigate how past experience facilitates functional connectivity during the comprehension of stories rich in perceptual and motor details. We found that comprehenders' past experience with the scenes and actions described in the narratives selectively modulated functional connectivity between lower‐ and higher‐level areas within the neural systems for visual and motor processing, respectively. These intramodal interactions may play an important role in integrating personal knowledge about a narrated situation with an evolving discourse representation. This study provides empirical evidence consistent with the idea that regions related to visual and motor processing are involved in the reenactment of experience as proposed by theories of embodied cognition. Hum Brain Mapp 36:1494–1505, 2015. © 2014 Wiley Periodicals, Inc.
Bornyl acetate has an anti‐inflammatory effect in human chondrocytes via induction of IL‐11
Authors: Yang He , Zhao Rugang , Chen Hao , Jia Pu , Bao Li , Tang Hai
Published: December 2014

Both pro‐inflammatory cytokines and anti‐inflammatory cytokines generated by chondrocytes play essential roles in the process of Rheumatoid arthritis and osteoarthritis (OA). Bornyl acetate is the main volatile constituent in numerous conifer oils and some Chinese traditional herbs, which has displayed an anti‐inflammatory effect before. In this study, we found that bornyl acetate elevates the expression of IL‐11 at both the mRNA and protein levels. Interestingly, our results indicated that IL‐1β‐mediated up‐regulation of IL‐6, IL‐8, MMP‐1, and MMP‐13 was significantly compromised by IL‐11 co‐treatment on mRNA levels and protein levels. The antagonistic effects of bornyl acetate on IL‐1β induced targets MMP‐1 and MMP‐13 were diminished by IL‐11 knockdown. Mechanistically, our results indicated that bornyl acetate significantly elevates the expression of AP‐1 component c‐fos, which may influence gross AP‐1 activity and initial the transcription of IL‐11. Indeed, expression of IL‐11 was reversed upon c‐fos knockdown. Our results suggest the therapeutic potentials of bornyl acetate in patients with OA. © 2014 IUBMB Life, 66(12):854–859, 2014
Rapid oriented fibril formation of fish scale collagen facilitates early osteoblastic differentiation of human mesenchymal stem cells
Authors: Matsumoto Rena , Uemura Toshimasa , Xu Zhefeng , Yamaguchi Isamu , Ikoma Toshiyuki , Tanaka Junzo
Published: December 2014

We studied the effect of fibril formation of fish scale collagen on the osteoblastic differentiation of human mesenchymal stem cells (hMSCs). We found that hMSCs adhered easily to tilapia scale collagen, which remarkably accelerated the early stage of osteoblastic differentiation in hMSCs during in vitro cell culture. Osteoblastic markers such as ALP activity, osteopontin, and bone morphogenetic protein 2 were markedly upregulated when the hMSCs were cultured on a tilapia collagen surface, especially in the early osteoblastic differentiation stage. We hypothesized that this phenomenon occurs due to specific fibril formation of tilapia collagen. Thus, we examined the time course of collagen fibril formation using high‐speed atomic force microscopy. Moreover, to elucidate the effect of the orientation of fibril formation on the differentiation of hMSCs, we measured ALP activity of hMSCs cultured on two types of tilapia scale collagen membranes with different degrees of fibril formation. The ALP activity in hMSCs cultured on a fibrous collagen membrane was significantly higher than on a non‐fibrous collagen membrane even before adding osteoblastic differentiation medium. These results showed that the degree of the fibril formation of tilapia collagen was essential for the osteoblastic differentiation of hMSCs. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2531–2539, 2015.
Association of QCT Bone Mineral Density and Bone Structure With Vertebral Fractures in Patients With Multiple Myeloma
Authors: Borggrefe Jan , Giravent Sarah , Thomsen Felix , Peña Jaime , Campbell Graeme , Wulff Asmus , Günther Andreas , Heller Martin , Glüer Claus C
Published: December 2014

Computed tomography (CT) is used for staging osteolytic lesions and detecting fractures in patients with multiple myeloma (MM). In the OsteoLysis of Metastases and Plasmacell-infiltration Computed Tomography 2 study (OLyMP-CT) study we investigated whether patients with and without vertebral fractures show differences in bone mineral density (BMD) or microstructure that could be used to identify patients at risk for fracture. We evaluated whole-body CT scans in a group of 104 MM patients without visible osteolytic lesions using an underlying lightweight calibration phantom (Image Analysis Inc., Columbia, KY, USA). QCT software (StructuralInsight) was used for the assessment of BMD and bone structure of the T11 or T12 vertebral body. Age-adjusted standardized odds ratios (sORs) per SD change were derived from logistic regression analyses, and areas under the receiver operating characteristics (ROC) curve (AUCs) analyses were calculated. Forty-six of the 104 patients had prevalent vertebral fractures (24/60 men, 22/44 women). Patients with fractures were not significantly older than patients without fractures (mean ± SD, 64 ± 9.2 versus 62 ± 12.3 years; p = 0.4). Trabecular BMD in patients with fractures versus without fractures was 169 ± 41 versus 192 ± 51 mg/cc (AUC = 0.62 ± 0.06, sOR = 1.6 [1.1 to 2.5], p = 0.02). Microstructural variables achieved optimal discriminatory power at bone thresholds of 150 mg/cc. Best fracture discrimination for single microstructural variables was observed for trabecular separation (Tb.Sp) (AUC = 0.72 ± 0.05, sOR = 2.4 (1.5 to 3.9), p < 0.0001). In multivariate models AUCs improved to 0.77 ± 0.05 for BMD and Tb.Sp, and 0.79 ± 0.05 for Tb.Sp and trabecular thickness (Tb.Th). Compared to BMD values, these improvements of AUC values were statistically significant (p < 0.0001). In MM patients, QCT-based analyses of bone structure derived from routine CT scans permit discrimination of patients with and without vertebral fractures. Rarefaction of the trabecular network due to plasma cell infiltration and osteoporosis can be measured. Deterioration of microstructural measures appear to be of value for vertebral fracture risk assessment and may indicate early stages of osteolytic processes not yet visible. © 2014 American Society for Bone and Mineral Research.
Extracorporeal photopheresis as a therapy for autoimmune diseases
Authors: Kuzmina Zoya , Stroncek David , Pavletic Steven Z.
Published: December 2014

Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency, irreversible organ damage and increased morbidity and mortality. Preventing or decreasing flares of AID correlate with durable disease control, significant reduction of inflammation and prevention of disability or therapy‐related toxicity. There is an urgent need for better treatment of severe, therapy‐refractory AID. Extracorporeal photopheresis (ECP) is a cell‐based immunomodulatory treatment which has been extensively used in variety of autoimmune disorders for the last two decades. ECP treatment is FDA approved for the treatment of cutaneous T‐cell lymphoma (CTCL) with particularly promising results seen in graft‐versus‐host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Prolonged therapy is safe, well tolerated and allows reduction of systemic immunosuppression in therapy‐refractory patients. Both clinical and experimental evidence suggest that ECP mechanism of action is characterized by apoptosis and phagocytosis of activated cells by antigen‐presenting cells (APC), secretion of anti‐inflammatory cytokines and stimulation of regulatory T cells (Tregs). The focus of this paper is to review the current evidence of ECP use in the treatment of AID. Here, we summarize the experience of nine major AID from 65 published reports. The key findings demonstrate substantial evidence of ECP feasibility, safety and in some AID also promising efficacy. However, the role of ECP in AID therapy is not established as most published studies are retrospective with limited number of patients and the trials are small or poorly standardized. The available data support future investigations of ECP as a therapeutic modality for the treatment of AID in well‐designed prospective clinical studies. J. Clin. Apheresis 30:224–237, 2015. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Eighteen years experience of granulocyte donations—acceptable donor safety?
Authors: Axdorph Nygell Ulla , Sollén‐Nilsson Agneta , Lundahl Joachim
Published: December 2014

Background: Granulocyte transfusions are given to patients with life‐threatening infections, refractory to treatment. The donors are stimulated with corticosteroids ± granulocyte colony stimulating factor (G‐CSF). However, data regarding the donors' safety is sparse. The objective was therefore to evaluate short‐ and long‐term adverse events (AE) in G‐CSF stimulated donors. Study design and methods: All consecutive granulocyte donors from 1994 to 2012 were identified through our registry. From the donation records, the number of aphereses, stimulation therapy, AE, blood values post donation, and recent status were evaluated. Results: One hundred fifty‐four volunteer donors were mobilized for 359 collections. Age at first granulocyte donation was 43 years (median; range 19–64 years). Follow‐up was 60 months (median; range 0–229 months). The dose of G‐CSF per collection was 3.8 ug/kg body weight (median; range 1.6–6.0 ug/kg). Sedimentation agent was HES. Short‐term AE were mild. Blood values 4 weeks post donation with minor reductions/elevations mostly resolved in later donations. Fourteen donors were excluded from the registry due to hypertension (4), diabetes (2), atrial flutter (1), breast carcinoma (1), urethral carcinoma in situ (1), MGUS (1), thrombosis (1), anaphylaxis (1), primary biliary cirrhosis (1), and unknown (1). Three donors are deceased due to diabetes, acute myocardial infarction, and unknown cause. All excluded/deceased donors except one were excluded/died at least 6 months after first granulocyte donation. Conclusion: No serious short‐term AE were observed. Due to the variability of diagnoses among excluded/deceased donors, we propose that it is less likely that granulocyte donations have a causative impact on these donors' exclusion or death. J. Clin. Apheresis 30:265–272, 2015. © 2014 Wiley Periodicals, Inc.
Correlation Between Abnormal Platelet Count and Respiratory Viral Infection in Patients From Cheonan, Korea
Authors: Kim Jae Kyung , Jeon Jae‐Sik , Kim Jong Wan , Kim Ga‐Yeon
Published: December 2014

Background

In this study, the effects of viral infections on platelet (PLT) count have been reported. This study examined the correlation between PLT count and respiratory virus (RV) infections.

Methods

Patients who visited Dankook University Hospital between December 2006 and February 2014 with symptoms of suspected RV infection were recruited. Multiplex reverse transcriptase polymerase chain reactions identified the causative virus(es). PLT counts were analyzed with respect to virus, age and sex of the patient, and length of hospital stay.

Results

Of the 8,147 patients, 62.8% were RV‐positive, and 18.6% of RV‐positive patients had abnormal PLT counts. There were no differences in the rates of abnormal PLT counts between single‐infection and virus co‐infection cases. In RV infection patients, the incidence of abnormal PLT count increased with age and varied depending on the RV infection type. Patients with abnormal PLT count stayed in hospital longer than those with normal PLT count.

Conclusions

The incidence of thrombocytopenia was higher among the elderly; in younger patients, thrombocytosis was more prevalent than thrombocytopenia. Respiratory tract infections caused by different viruses resulted in varied PLT count changes. Further systematic research of PLT count changes related to viral infections is required.