bluuebunny/crossref_metadata_2025 huggingface dataset:
Convenient Synthesis of Diaryliodonium Salts for the Production of [18F]F‐DOPA
Authors: Edwards Richard , Westwell Andrew D. , Daniels Stephen , Wirth Thomas
Published: December 2014

[18F]F‐DOPA is an important radiotracer that is used in the diagnosis of Parkinson's disease and neuroendocrine tumours. We describe a simple synthesis for a number of diaryliodonium salt precursors that are suitable for the production of [18F]F‐DOPA through reaction with no carrier added (n.c.a.) nucleophilic [18F]fluoride. The simple procedure gives bench‐stable, complex iodonium precursors in good yields without the need for laborious anhydrous conditions. Further alteration to the precursor counterion can be readily achieved for a range of halides and pseudo halides by a simple modification of the workup. Preliminary “hot” and “cold” fluorination results show the suitability of the compounds for the production of [18F]F‐DOPA.
Multisite musculoskeletal pain predicts medically certified disability retirement among Finns
Authors: Haukka E. , Kaila‐Kangas L. , Ojajärvi A. , Saastamoinen P. , Holtermann A. , Jørgensen M.B. , Karppinen J. , Heliövaara M. , Leino‐Arjas P.
Published: December 2014

Background

Musculoskeletal pain at several sites (multisite pain) is more common than single‐site pain. Little is known on its effects on disability pension (DP) retirement.

Methods

A nationally representative sample comprised 4071 Finns in the workforce aged 30 to 63. Data (questionnaire, interview, clinical examination) were gathered in 2000–2001 and linked with national DP registers for 2000–2011. Pain during the preceding month in 18 locations was combined into four sites (neck, upper limbs, low back, lower limbs). Hazard ratios (HR) of DP were estimated by Cox regression.

Results

The HR of any DP (n = 477) was 1.6 (95% confidence interval 1.2–2.1) for one, 2.5 (1.9–3.3) for two, 3.1 (2.3–4.3) for three and 5.6 (4.0–7.8) for four pain sites, when adjusted for age and gender. When additionally adjusted for clinically assessed chronic diseases, the HRs varied from 1.4 (1.0–1.8) to 3.5 (2.5–4.9), respectively. When further adjusted for physical and psychosocial workload, education, body mass index, smoking, exercise and sleep disorders, the HRs were 1.3 (0.9–1.7), 1.6 (1.2–2.2), 1.8 (1.3–2.5) and 2.5 (1.8–3.6). The number of pain sites was especially strong in predicting DPs due to musculoskeletal diseases (HRs in the full model; 3.1 to 4.3), but it also predicted DPs due to other somatic diseases (respective HRs 1.3 to 2.3); pain in all four sites was also predictive of DPs due to mental disorders (full model HR 2.2).

Conclusions

The number of pain sites independently predicted DP retirement. Employees with multisite pain may need specific support to maintain their work ability.
Different relational models underlie prototypical left and right positions on social issues
Authors: Simpson Ain , Laham Simon M.
Published: December 2014

Social issues are important dividing lines in the “culture wars” between the political left and right. Despite much research into social issue stance and ideology, little research has explored these with Relational Models Theory (RMT). RMT proposes four distinct models that people use to construe social relations, each entailing distinct moral considerations. In two studies, participants read summaries of the models, rated how relevant each was to their positions on several social issues (e.g., capital punishment), and expressed issue positions. In Study 1, Communal Sharing and Equality Matching construals predicted prototypical liberal positions across a range of issues; Authority Ranking and Market Pricing construals predicted prototypical conservative positions. By using multilevel modelling in Study 2, individual differences in average Communal Sharing and Authority Ranking construals predicted prototypical liberal and conservative positions, respectively, independent of several factors known to predict social issue stance. In issue‐specific analyses (e.g., focusing on euthanasia), all models showed effects independent of self‐reported ideology, while for certain issues (same‐sex marriage, animal testing, gun control, and flag burning), issue construal using different models predicted opposing positions, implicating relational models in moral disagreement. This paper provides novel tests of Relationship Regulation Theory and suggests that RMT is relevant in understanding political ideology, social issue stance, and moral judgement. Copyright © 2014 John Wiley & Sons, Ltd.
Voltammetric Determination of Folic Acid Using a Graphite Paste Electrode
Authors: Gonçalves de Araújo Eliane , Fernandes Nedja Suely , da Silva Solon Lilian Grace , Soares Aragão Cícero Flavio , Martinez‐Huitle Carlos A.
Published: December 2014

A simple differential pulse voltammetric method based on a graphite paste electrode (GPE) was developed for the quantitative determination of folic acid (FA) in tablets. The electrode exhibits a clear improvement of the current response. A linear response in the electroanalytical approach exists from 4.97×10−6 to 2.94×10−5 mol L−1 with a limit of detection of about 2.67×10−6 mol L−1 in KCl solutions. The developed procedure was tested by recovery studies and compared with spectrophotometric and chromatographic methods. The results are described and discussed in the light of existing literature.
Dual Biosensing Device for the Speciation of Arsenic
Authors: del Torno‐de Román Lorena , Alonso‐Lomillo M. Asunción , Domínguez‐Renedo Olga , Arcos‐Martínez M. Julia
Published: December 2014

Acetylcholinesterase (ACh) and acid phosphatase (AcP) have been simultaneously cross‐linked onto an array of SPCEs, which was set up by a Ag/AgCl reference electrode, a carbon counter electrode and two carbon working electrodes. The detection of As(III) and As(V) is based on their enzymatic inhibitory effect. Different immobilization conditions, substrates, supporting electrolytes and chronoamperometric experimental conditions have been studied for the sensitive and selective detection of both species of arsenic in complex matrices, such as tap water and wine, at once.
Analysis of the role of the particle–wall interaction on the separation efficiencies of field flow fractionation dielectrophoretic devices
Authors: Camarda Massimo , Scalese Silvia , La Magna Antonino
Published: December 2014

In this paper we have used both analytical models and finite element simulations to analyze the role of the particle–wall dipole interaction in field‐flow fractionation dielectrophoretic (FFF‐DEP) devices. We identify the existence of “anomalous” regions where the dielectrophoretic response is altered, independently of the complex dielectric permittivity of the particles and suspending medium. In these regions the interaction between the particle and the conductive (isolating) walls induces cohesive (repulsive) forces, independently of the Clausius–Mossotti term. We quantify the impact of such an effect, which can critically decrease the specificity and sensitivity of both continuous‐ and batch‐mode FFF‐DEP. We find a scale invariant relation correlating the particles radius (Rp) and the electrodes width (Wel), which permits the design of dielectrophoretic schema capable of avoiding the generation of such regions. Specifically, to avoid the generation of the anomalous DEP regions, Wel should be chosen smaller than ∼5.2 Rp. For this reason, interdigitate schema with electrode widths of 14 μm and gaps of 50 μm could improve the separation efficiency of FFF‐DEP devices in the case of rare cells separation in blood samples.
Opportunities to integrate new approaches in genetic toxicology: An ILSI‐HESI workshop report
Authors: Zeiger Errol , Gollapudi Bhaskar , Aardema Marilyn J. , Auerbach Scott , Boverhof Darrell , Custer Laura , Dedon Peter , Honma Masamitsu , Ishida Seiichi , Kasinski Andrea L. , Kim James H. , Manjanatha Mugimane G. , Marlowe Jennifer , Pfuhler Stefan , Pogribny Igor , Slikker William , Stankowski Leon F. , Tanir Jennifer Y. , Tice Raymond , van Benthem Jan , White Paul , Witt Kristine L. , Thybaud Véronique
Published: December 2014

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI‐HESI) Committee on the Relevance and Follow‐up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided. Environ. Mol. Mutagen. 56:277–285, 2015. © 2014 Wiley Periodicals, Inc.
Can the comet assay be used reliably to detect nanoparticle‐induced genotoxicity?
Authors: Karlsson Hanna L. , Di Bucchianico Sebastiano , Collins Andrew R. , Dusinska Maria
Published: December 2014

The comet assay is a sensitive method to detect DNA strand breaks as well as oxidatively damaged DNA at the level of single cells. Today the assay is commonly used in nano‐genotoxicology. In this review we critically discuss possible interactions between nanoparticles (NPs) and the comet assay. Concerns for such interactions have arisen from the occasional observation of NPs in the “comet head”, which implies that NPs may be present while the assay is being performed. This could give rise to false positive or false negative results, depending on the type of comet assay endpoint and NP. For most NPs, an interaction that substantially impacts the comet assay results is unlikely. For photocatalytically active NPs such as TiO2, on the other hand, exposure to light containing UV can lead to increased DNA damage. Samples should therefore not be exposed to such light. By comparing studies in which both the comet assay and the micronucleus assay have been used, a good consistency between the assays was found in general (69%); consistency was even higher when excluding studies on TiO2 NPs (81%). The strong consistency between the comet and micronucleus assays for a range of different NPs—even though the two tests measure different endpoints—implies that both can be trusted in assessing the genotoxicity of NPs, and that both could be useful in a standard battery of test methods. Environ. Mol. Mutagen. 56:82–96, 2015. © 2014 Wiley Periodicals, Inc.
Inter- and intraspecies chemical sensitivity: A case study using 2,4-dinitroanisole
Authors: Kennedy Alan J. , Laird Jennifer G. , Lounds Chris , Gong Ping , Barker Natalie D. , Brasfield Sandra M. , Russell Amber L. , Johnson Mark S.
Published: December 2014

Insensitive munitions offer increased safety because of their “insensitivity” to unintended detonation relative to historically used formulations such as 2,4,6-trinitrotoluene (TNT). Dinitroanisole (DNAN) is an insensitive munition constituent, and its solubility and stability warrant investigations of potential toxicological hazard related to manufacturing discharges and training ranges. Although ecotoxicology data are available for other insensitive munition constituents, few data are available for DNAN. In the present study, acute and chronic exposures of a fish (Pimephales promelas) and 2 cladocerans (Ceriodaphnia dubia, Daphnia pulex) were conducted. The 50% lethal concentration (LC50) values of DNAN ranged from 14.2 mg/L to 42.0 mg/L, depending on species. In chronic exposures, fish survival (LC50 = 10.0 mg/L) was more sensitive than cladoceran survival (LC50 = 13.7 to >24.2 mg/L). However, cladoceran reproduction was equally or more sensitive to DNAN (50% inhibition values 2.7–10.6 mg/L, depending on species) than fish endpoints. Daphnia pulex was the most sensitive species, with only slight differences between the 3 populations tested. Although the aquatic toxicity of DNAN was lower than previously reported in the literature for TNT, future research is needed to determine the potential synergistic toxicity of all the constituents in insensitive munition mixtures and the implications of photo-oxidation. Environ Toxicol Chem 2014;9999:1–10. © 2014 SETAC
GEMAS: Prediction of solid-solution phase partitioning coefficients (Kd) for oxoanions and boric acid in soils using mid-infrared diffuse reflectance spectroscopy
Authors: Janik Leslie J. , Forrester Sean T. , Soriano-Disla José M. , Kirby Jason K. , McLaughlin Michael J. , Reimann Clemens ,   The GEMAS Project Team
Published: December 2014

The authors' aim was to develop rapid and inexpensive regression models for the prediction of partitioning coefficients (Kd), defined as the ratio of the total or surface-bound metal/metalloid concentration of the solid phase to the total concentration in the solution phase. Values of Kd were measured for boric acid (B[OH]30) and selected added soluble oxoanions: molybdate (MoO42–), antimonate (Sb[OH]6–), selenate (SeO42–), tellurate (TeO42–) and vanadate (VO43–). Models were developed using approximately 500 spectrally representative soils of the Geochemical Mapping of Agricultural Soils of Europe (GEMAS) program. These calibration soils represented the major properties of the entire 4813 soils of the GEMAS project. Multiple linear regression (MLR) from soil properties, partial least-squares regression (PLSR) using mid-infrared diffuse reflectance Fourier-transformed (DRIFT) spectra, and models using DRIFT spectra plus analytical pH values (DRIFT + pH), were compared with predicted log Kd + 1 values. Apart from selenate (R2 = 0.43), the DRIFT + pH calibrations resulted in marginally better models to predict log Kd + 1 values (R2 = 0.62–0.79), compared with those from PSLR-DRIFT (R2 = 0.61–0.72) and MLR (R2 = 0.54–0.79). The DRIFT + pH calibrations were applied to the prediction of log Kd + 1 values in the remaining 4313 soils. An example map of predicted log Kd + 1 values for added soluble MoO42– in soils across Europe is presented. The DRIFT + pH PLSR models provided a rapid and inexpensive tool to assess the risk of mobility and potential availability of boric acid and selected oxoanions in European soils. For these models to be used in the prediction of log Kd + 1 values in soils globally, additional research will be needed to determine if soil variability is accounted on the calibration. Environ Toxicol Chem 2014;9999:1–12. © 2014 SETAC
Cardiac toxicity by sublethal 2,3,7,8-tetrachlorodibenzo-p-dioxin correlates with its anti-proliferation effect on cardiomyocytes in zebrafish embryos
Authors: Chen Jing
Published: December 2014

The cardiac toxicity of zebrafish embryos in response to the lethal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well characterized. Dioxin contamination levels in nature are usually lower, however, and sublethal TCDD toxicity is less investigated. The present study found that the nonlethal doses of TCDD for 72-h-postfertilization (hpf) zebrafish embryos were 25 pg/mL and lower. For the present study, sublethal TCDD concentrations of 10 pg/mL and 25 pg/mL were selected, and their toxicity was then characterized. The results showed that embryos still exhibited acute and subchronic cardiac toxicity at these 2 dosages. The stroke volume and cardiac output of these embryos significantly declined early until 8 d postexposure. Embryos' heart size became smaller, and the hearts contained fewer cardiomyocytes per heart, with decreased cardiomyocyte proliferation. Apoptosis was not detected either in the TCDD-treated or the control hearts. Real-time polymerase chain reaction (PCR) revealed that the transcription of a battery of cell-cycle–related genes was suppressed within the sublethal TCDD-treated heart. In contrast, embryonic jaw development seemed not to be affected. The present study suggests that dioxin contamination, even at lower levels, might lead to cardiac toxicity in fish embryos. Such cardiac toxicity presents as disrupted normal heart function, originating from the anti-proliferative effect of sublethal TCDD on cardiomyocytes. Environ Toxicol Chem 2014;9999:1–9. © 2014 SETAC
Inhibition effect of Na+ and Ca2+ on the bioaccumulation of perfluoroalkyl substances by Daphnia magna in the presence of protein
Authors: Xia Xinghui , Rabearisoa Andry Harinaina , Dai Zhineng , Jiang Xiaoman , Zhao Pujun , Wang Haotian
Published: December 2014

The authors investigated the individual effects of Ca2+ and Na+ on the bioaccumulation of 6 types of perfluoroalkyl substances (PFASs), including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorododecanoic acid (PFDoA), by Daphnia magna in water with 10 mg L−1 bovine albumin or soy peptone. The bioaccumulation factors of PFASs by D. magna decreased linearly with the increase of Ca2+ and Na+ concentrations. The inhibition effect of Ca2+ was stronger than that of Na+, and the decreasing percentages of the body burden of PFASs in D. magna caused by the increment of 1 mmol L−1 Ca2+ and 1 mmol L−1 Na+ were 41% to approximately 48% and 2% to approximately 5%, respectively, in the presence of soy peptone. The partition coefficients (Kp) of PFASs between protein and water increased with rising Ca2+ and Na+ concentrations. The elevated Kp values led to the reduced concentrations of freely dissolved PFASs. This resulted in a decrease of PFAS bioaccumulation in D. magna, and the body burden of each PFAS was positively correlated with its freely dissolved concentration in water. The present study suggests that cations should be considered in the assessment of bioavailability and risk of PFASs in natural waters containing proteinaceous compounds. Environ Toxicol Chem 2014;9999:1–8. © 2014 SETAC
Zebra mussels (Dreissena polymorpha) as a biomonitor of trace elements along the southern shoreline of Lake Michigan
Authors: Shoults-Wilson W. Aaron , Elsayed Norhan , Leckrone Kristen , Unrine Jason
Published: December 2014

The invasive zebra mussel (Dreissena polymorpha) has become an accepted biomonitor organism for trace elements, but it has yet to be studied along the Lake Michigan shoreline. Likewise, the relationships between tissue concentrations of elements, organism size, and sediment concentrations of elements have not been fully explained. The present study found that a variety of allometric variables such as length, dry tissue mass, shell mass, organism condition indices, and shell thickness index were useful in explaining intrasite variability in elemental concentrations. The flesh condition index (grams of tissue dry mass per gram of shell mass) explained variability at the most sites for most elements. Once allometric intrasite variability was taken into account, additional significant differences were found between sites, although the net effect was small. Significant positive relationships between sediment and tissue concentrations were found for Pb and Zn, with a significant negative relationship for Cd. It was also found that Cu and Zn concentrations in tissues increased significantly along the shoreline in the southeasterly direction, whereas Hg increased in a northwesterly direction. Opportunistic sampling found that zebra mussels accumulate significantly higher concentrations of nearly all elements analyzed compared to Asian clams (Corbicula fluminea) at the same site. The present study demonstrates the need to fully explain natural sources of variability before using biomonitors to explain spatial distributions of trace elements. Environ Toxicol Chem 2014;9999:1–8. © 2014 SETAC
Influence of water quality on zinc toxicity to the Florida apple snail (Pomacea paludosa) and sensitivity of freshwater snails to zinc
Authors: Hoang Tham C. , Tong Xin
Published: December 2014

The present study characterized the influence of water-quality characteristics on zinc (Zn) toxicity to the Florida apple snail (Pomacea paludosa) and the sensitivity of freshwater snails to Zn. Standard 96-h renewal acute toxicity tests were conducted with Zn and juvenile P. paludosa under 3 conditions of pH and alkalinity, water hardness, and dissolved organic carbon (DOC). Median lethal effect concentrations (96-h LC50s), no-observed- effect concentrations, lowest-observed-effect concentrations, LC10s, and LC20s were determined for each test. The results showed that Zn toxicity to P. paludosa decreased linearly with increasing hardness, pH, and DOC. A multiple linear regression model based on pH, hardness, and DOC was able to explain 99% of the observed variability in LC50s. These results are useful for the development of a biotic ligand model (BLM) for P. paludosa and Zn. Zinc acute toxicity data were collected from the literature for 12 freshwater snail species in a wide range of water-quality characteristics for species sensitivity distribution analysis. The results showed that P. paludosa is the second most sensitive to Zn. The present study also suggested that aqueous ZnCO3 and ZnHCO3– can be bioavailable to P. paludosa. Therefore, bioavailability models (e.g., BLM) should take these Zn species into consideration for bioavailability when applied to snails. Environ Toxicol Chem 2015;34:545–553. © 2014 SETAC
The Log‐Linear Cognitive Diagnostic Model (LCDM) as a Special Case of the General Diagnostic Model (GDM)
Authors: von Davier Matthias
Published: December 2014

Diagnostic models combine multiple binary latent variables in an attempt to produce a latent structure that provides more information about test takers' performance than do unidimensional latent variable models. Recent developments in diagnostic modeling emphasize the possibility that multiple skills may interact in a conjunctive way within the item function, while individual skills still may retain separable additive effects. This extension of either the conjunctive deterministic‐input‐noisy‐and (DINA) model to the generalized version (G‐DINA) or the compensatory/additive general diagnostic model (GDM) to the log‐linear cognitive diagnostic model (LCDM) is aimed at integrating models with conjunctive skills and those that assume compensatory functioning of multiple skill variables. More recently, a result was proven mathematically that the fully conjunctive DINA model, which combines all required skills in a single binary function, may be recast as a compensatory special case of the GDM. This can be accomplished in more than one form such that the resulting transformed skill‐space definitions and design (Q) matrices are different from each other but mathematically equivalent to the DINA model, producing identical model‐based response probabilities. In this report, I extend this equivalency result to the LCDM and show that a mathematically equivalent, constrained GDM can be defined that yields identical parameter estimates based on a transformed set of compensatory skills.
Kronecker product‐based codebook design and optimisation for correlated 3D channels
Authors: Wang Ying , Jiang Lisi , Chen Yongce
Published: December 2014

Discrete Fourier transform (DFT) codebook has been favoured by long term evolution because of its simplicity and effectiveness for two‐dimensional multi‐input multi‐output channels. In order to further explore vertical freedom, a Kronecker product‐based codebook (KPC), which is the Kronecker product of a horizontal DFT codebook and a vertical one, has been proposed. However, how to effectively design the codebook is still a challenge, because neither its effectiveness nor optimisation has been studied. In this paper, we demonstrate that the codewords in the KPC approximately match the distribution of the optimal beamforming vectors under spatially correlated three‐dimensional channels, showing the effectiveness of such codebook structure. Moreover, because the maximal cross‐correlation amplitude (Imax) of the original KPC is high, we investigate the structure of the codebook and then find a criterion of constructing the optimal KPC to achieve the lowest Imax, namely the Welch bound. Furthermore, considering the optimal codebook only exists under certain conditions, a modified discrete stochastic approximation algorithm is used to construct a near‐optimal codebook. Simulation results show that our algorithm greatly reduces Imax and respectively provides 1 and 0.5 dB coding gain compared to the traditional DFT codebook and the original KPC, which confirms the efficiency of the codebook design. Copyright © 2014 John Wiley & Sons, Ltd.
Heat penetration and thermocouple location in home canning
Authors: Etzel Mark R. , Willmore Paola , Ingham Barbara H.
Published: December 2014

We processed applesauce, tomato juice, and cranberries in pint jars in a boiling water canner to test thermal processing theories against home canning of high‐acid foods. For each product, thermocouples were placed at various heights in the jar. Values for fh (heating), fcl (cooling), and F82.2°C (lethality) were determined for each thermocouple location, and did not depend substantially on thermocouple location in accordance with heat transfer theory. There was a cold spot in the jar, but the cold spot during heating became the hot spot during cooling. During heating, the geometric center was the last to heat, and remained coldest the longest, but during coooling, it was also the last to cool, and remained hottest the longest. The net effect was that calculated lethality in home canning was not affected by thermocouple location. Most of the lethality during home canning occurred during air cooling, making cooling of home canned foods of great importance. Calculated lethality was far greater than the required 5‐log reduction of spores in tomato juice and vegetative cells in cranberries, suggesting a wide margin of safety for approved home‐canning processes for high‐acid foods.
CAUSES FOR CONCERN: IS NICE FAILING TO UPHOLD ITS RESPONSIBILITIES TO ALL NHS PATIENTS?
Authors: Claxton Karl , Sculpher Mark , Palmer Stephen , Culyer Anthony J
Published: December 2014

Organisations across diverse health care systems making decisions about the funding of new medical technologies face extensive stakeholder and political pressures. As a consequence, there is quite understandable pressure to take account of other attributes of benefit and to fund technologies, even when the opportunity costs are likely exceed the benefits they offer. Recent evidence suggests that NICE technology appraisal is already approving drugs where more health is likely to be lost than gained. Also, NICE recently proposed increasing the upper bound of the cost‐effectiveness threshold to reflect other attributes of benefit but without a proper assessment of the type of benefits that are expected to be displaced. It appears that NICE has taken a direction of travel, which means that more harm than good is being, and will continue to be, done, but it is unidentified NHS patients who bear the real opportunity costs. Copyright © 2014 John Wiley & Sons, Ltd.
Challenging the need for random directed biopsies of the nasopharynx, pyriform sinus, and contralateral tonsil in the workup of unknown primary squamous cell carcinoma of the head and neck
Authors: Tanzler Emily D. , Amdur Robert J. , Morris Christopher G. , Werning John W. , Mendenhall William M.
Published: December 2014

Background

Many guidelines recommend random directed biopsies of the nasopharynx, contralateral tonsil, and hypopharynx to evaluate an unknown primary squamous cell carcinoma of the head and neck. There are no published data documenting the need for these recommendations. The purpose of our study was to report the rate of positive blind biopsies in this setting.

Methods

We recorded the rate of positive random directed biopsies performed as part of the workup for 156 patients treated with radiotherapy between 1985 and 2014 for an unknown primary squamous cell carcinoma presenting with the main location of adenopathy in nodal stations 2, 3, 4, or 5.

Results

Rate of positive result by subsite: nasopharynx and pyriform sinus = 0%; tonsillectomy: ipsilateral = 39%, bilateral = 6%; and base of tongue = 18%.

Conclusion

With modern imaging, random directed biopsies of the nasopharynx and hypopharynx are unnecessary in the workup of unknown primary squamous cell carcinoma of the head and neck. © 2015 Wiley Periodicals, Inc. Head Neck 38: 578–581, 2016
Oropharyngeal cancer as a driver of racial outcome disparities in squamous cell carcinoma of the head and neck: 10‐year experience at the University of Maryland Greenebaum Cancer Center
Authors: Zandberg Dan P. , Liu Sandy , Goloubeva Olga , Ord Robert , Strome Scott E. , Suntharalingam Mohan , Taylor Rodney , Morales Robert E. , Wolf Jeffrey S. , Zimrin Ann , Lubek Joshua E. , Schumaker Lisa M. , Cullen Kevin J.
Published: December 2014

Background

Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients.

Methods

We retrospectively analyzed 1318 patients with primary HNSCC treated at the University of Maryland Greenebaum Cancer Center (UMGCC) from 2000 to 2010.

Results

Of all the patients, 65.9% were white, 30.7% were black, and 3.3% were of other races. Black patients were less likely to present with oral cavity cancer, and more likely to present with laryngeal or hypopharyngeal cancers. White patients were more likely to have early stage disease, especially in the oral cavity. Black race was independently associated with worse overall survival (OS) in the entire cohort. Black patients had a significantly worse OS among oral cavity and oropharyngeal cancers, with the largest disparity in oropharyngeal cancer. However, in multivariate analysis, race was only still significant in oropharyngeal cancer.

Conclusion

We observed differences by race in distribution of disease site, stage, and OS. Survival disparity in the entire cohort was driven mostly by differences among oropharyngeal cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: 564–572, 2016
Traction injury of the recurrent laryngeal nerve: Results of continuous intraoperative neuromonitoring in a swine model
Authors: Lee Hye Yoon , Cho Young Geon , You Ji Young , Choi Byoung Ho , Kim Joon Yub , Wu Che‐Wei , Chiang Feng‐Yu , Kim Hoon Yub
Published: December 2014

Background

Recurrent laryngeal nerve (RLN) palsy is the most serious complication after thyroidectomy. However, little is known about the degree of traction injury that causes loss of signal. The purpose of this study was to evaluate traction injuries in the swine RLN using continuous intraoperative neuromonitoring (IONM) and determine the traction power that results in loss of signal.

Methods

Thirteen swine underwent traction injury to the RLNs with continuous IONM, and stress‐strain curves were determined for 8 nerves using the universal material testing machine in an ex vivo model.

Results

Traction injury at a mean power of 2.83 MPa caused loss of signal. The mean physiologic limit strain and tensile strength of the swine RLNs were found to be 15.0% and 4.9 MPa, respectively. Histological analysis showed no abnormal structural findings.

Conclusion

Traction injury of swine RLNs causes loss of signal at a power of 2.83 MPa. However, all injured nerves recovered within 7 days with no observed structural damage. © 2015 Wiley Periodicals, Inc. Head Neck 38: 582–588, 2016
Impact of postoperative magnesium levels on early hypocalcemia and permanent hypoparathyroidism after thyroidectomy
Authors: Garrahy Aoife , Murphy Matthew S. , Sheahan Patrick
Published: December 2014

Background

Postoperative hypocalcemia is a common complication of thyroidectomy. Magnesium is known to modulate serum calcium levels and hypomagnesemia may impede correction of hypocalcemia. The purpose of this study was to investigate whether hypomagnesemia after thyroidectomy has any impact on early hypocalcemia and/or permanent hypoparathyroidism.

Methods

We conducted a retrospective review of prospectively maintained databases. Inclusion criteria were total or completion total thyroidectomy with postoperative magnesium levels available. The incidence of postoperative hypocalcemia was correlated with postoperative hypomagnesemia and other risk factors.

Results

Two hundred one cases were included. Twenty‐six patients (13%) developed postoperative hypomagnesemia. Hypomagnesemia (p = .002), cancer diagnosis (p = .01), central neck dissection (p = .02), and inadvertent parathyroid resection (p = .02) were significantly associated with hypocalcemia. On multivariate analysis, only hypomagnesemia (p = .005) remained significant. Hypomagnesemia was also a significant predictor of permanent hypoparathyroidism (p = .0004).

Conclusion

Hypomagnesemia is significantly associated with early hypocalcemia and permanent hypoparathyroidism after thyroidectomy. Magnesium levels should be closely monitored in patients with postthyroidectomy hypocalcemia. © 2015 Wiley Periodicals, Inc. Head Neck 38: 613–619, 2016
The mTOR and canonical Wnt signaling pathways mediate the mnemonic effects of progesterone in the dorsal hippocampus
Authors: Fortress Ashley M. , Heisler John D. , Frick Karyn M.
Published: December 2014

Although much is known about the neural mechanisms responsible for the mnemonic effects of 17β‐estradiol (E2), very little is understood about the mechanisms through which progesterone (P4) regulates memory. We previously showed that intrahippocampal infusion of P4 in ovariectomized female mice enhances object recognition (OR) memory consolidation in a manner dependent on activation of dorsal hippocampal ERK and mTOR signaling. However, the role of specific progesterone receptors (PRs) in mediating the effects of progesterone on memory consolidation and hippocampal cell signaling are unknown. Therefore, the goals of this study were to investigate the roles of membrane‐associated and intracellular PRs in mediating hippocampal memory consolidation, and identify downstream cell signaling pathways activated by PRs. Membrane‐associated PRs were targeted using bovine serum albumin‐conjugated progesterone (BSA‐P), and intracellular PRs (PR‐A, PR‐B) were targeted using the intracellular PR agonist R5020. Immediately after OR training, ovariectomized mice received bilateral dorsal hippocampal infusion of vehicle, P4, BSA‐P, or R5020. OR memory consolidation was enhanced by P4, BSA‐P, and R5020. However, only P4 and BSA‐P activated ERK and mTOR signaling. Furthermore, dorsal hippocampal infusion of the ERK inhibitor U0126 blocked the memory‐enhancing effects of BSA‐P, but not R5020. The intracellular PR antagonist RU486 blocked the memory‐enhancing effects of R5020, but not BSA‐P. Interestingly, P4 robustly activated canonical Wnt signaling in the dorsal hippocampus, which is consistent with our recent findings that canonical Wnt signaling is necessary for OR memory consolidation. R5020, but not BSA‐P, also elicited a modest increase in canonical Wnt signaling. Collectively, these data suggest that activation of ERK signaling is necessary for membrane‐associated PRs to enhance OR, and indicate a role for canonical Wnt signaling in the memory‐enhancing effects of intracellular PRs. This study provides the first evidence that membrane and intracellular PRs may employ different molecular mechanisms to enhance hippocampal memory. © 2014 Wiley Periodicals, Inc.
Chaperoned amyloid proteins for immune manipulation: α‐Synuclein/Hsp70 shifts immunity toward a modulatory phenotype
Authors: Labrador‐Garrido Adahir , Cejudo‐Guillén Marta , Klippstein Rebecca , De Genst Erwin J. , Tomas‐Gallardo Laura , Leal María M. , Villadiego Javier , Toledo‐Aral Juan J. , Dobson Christopher M. , Pozo David , Roodveldt Cintia
Published: December 2014

α‐Synuclein (αSyn) is a 140‐residue amyloid‐forming protein whose aggregation is linked to Parkinson's disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective αSyn‐based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat‐shock proteins (HSPs): their classical “chaperone” activities and their recently discovered and diverse “immunoactive” properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an αSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the αSyn/Hsp70 complex, including a restrained αSyn‐specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4+CD25+Foxp3+) and Teff (CD4+Foxp3−) cell populations, as opposed to significant changes in mice immunized with αSyn and Hsp70 alone. Furthermore, in vitro‐stimulated splenocytes from immunized mice showed the lowest relative response against αSyn challenge for the “αSyn/Hsp70” experimental group as measured by IFN‐γ and IL‐17 secretion, and higher IL‐10 levels when stimulated with LPS. Finally, serum levels of Th1‐cytokine IFN‐γ and immunomodulatory IL‐10 indicated a unique shift toward an immunomodulatory/immunoprotective phenotype in mice immunized with the αSyn/Hsp70 complex. Overall, we propose the use of functional “HSP‐chaperoned amyloid/aggregating proteins” generated with appropriate HSP‐substrate protein combinations, such as the αSyn/Hsp70 complex, as a novel strategy for immune‐based intervention against synucleinopathies and other amyloid or “misfolding” neurodegenerative disorders.
Paracrine regulation of glioma cells invasion by astrocytes is mediated by glial‐derived neurotrophic factor
Authors: Shabtay‐Orbach Ayelet , Amit Moran , Binenbaum Yoav , Na'ara Shorook , Gil Ziv
Published: December 2014

It was suggested that the brain microenvironment plays a role in glioma progression. Here we investigate the mechanism by which astrocytes which are abundant in glioma tumors, promote cancer cell invasion. In this study, we evaluated the effects of astrocytes on glioma biology both in vitro and in vivo and determined the downstream paracrine effect of glial‐derived neurotrophic factor (GDNF) on tumor invasion. Astrocytes‐conditioned media (ACM) significantly increased human and murine glioma cells migration compared to controls. This effect was inhibited when the activity of GDNF on glioma cells was blocked by RET‐Fc chimera or anti‐GDNF Ab and by small interfering RNA directed against GDNF expression by astrocytes. Glioma cells incubated with ACM led to time dependent phosphorylation of the GDNF receptor, RET and downstream activation of AKT. Tumor migration and GDNF‐RET‐AKT activation was inhibited by the RET small‐molecule inhibitor pyrazolopyrimidine‐1 (PP1) and by the AKT inhibitor LY294002. Finally, blocking of RET by PP1 or knockout of the RET coreceptor GFRα1 in glioma cells reduced the size of brain tumors in immunocompetent mice. We suggest a mechanism by which astrocytes attracted to the glioma tumors facilitate brain invasion by secretion of GDNF and activation of RET/GFRα1 receptors expressed by the cancer cells.
Cell‐surface Vimentin: A mislocalized protein for isolating csVimentin+CD133− novel stem‐like hepatocellular carcinoma cells expressing EMT markers
Authors: Mitra Abhisek , Satelli Arun , Xia Xueqing , Cutrera Jeffrey , Mishra Lopa , Li Shulin
Published: December 2014

Recent advances in cancer stem cell biology have shown that cancer stem‐like cells with epithelial–mesenchymal transition (EMT) phenotypes are more aggressive and cause relapse; however, absence of a specific marker to isolate these EMT stem‐like cells hampers research in this direction. Cell surface markers have been identified for isolating cancer stem‐like cells, but none has been identified for isolating cancer stem‐like cells with EMT phenotype. Recently, we discovered that Vimentin, an intracellular EMT tumor cell marker, is present on the surface of colon metastatic tumor nodules in the liver. In our study, we examined the potential of targeting cell surface Vimentin (CSV) to isolate stem‐like cancer cells with EMT phenotype, by using a specific CSV‐binding antibody, 84‐1. Using this antibody, we purified the CSV‐positive, CD133‐negative (csVim+CD133−) cell population from primary liver tumor cell suspensions and characterized for stem cell properties. The results of sphere assays and staining for the stem cell markers Sox2 and Oct4A demonstrated that csVim+CD133− cells have stem‐like properties similar to csVim−CD133+ population. Our investigation further revealed that the csVim+CD133− cells had EMT phenotypes, as evidenced by the presence of Twist and Slug in the nucleus, the absence of EpCAM on the cell surface and basal level of expression of epithelial marker E‐cadherin. The csVimentin‐negative CD133‐positive stem cells do not have any EMT phenotypes. csVim+CD133− cells exhibited more aggressively metastatic in livers than csVim−CD133+ cells. Our findings indicate that csVim+CD133− cells are promising targets for treatment and prevention of metastatic hepatocellular carcinoma.
An evaluation and replication of miRNAs with disease stage and colorectal cancer‐specific mortality
Authors: Slattery Martha L. , Herrick Jennifer S. , Mullany Lila E. , Valeri Nicola , Stevens John , Caan Bette J. , Samowitz Wade , Wolff Roger K.
Published: December 2014

MicroRNAs (miRNAs) have been implicated in colorectal cancer (CRC) development and associated with prognostic indicators such as disease stage and survival. Prognostic associations are often based on few individuals and imprecise. In this study, we utilize population‐based data from 1,141 CRC cases to replicate previously reported associations between 121 miRNAs and disease stage and survival. The Agilent Human miRNA Microarray V19.0 was used to generate miRNA data following a stringent quality control protocol. Assessment of survival was done using Cox Proportional Hazard models adjusting for age, disease stage and tumor molecular phenotype. Five miRNAs were associated with more advanced disease stage; hsa‐miR‐145‐5p and hsa‐miR‐31‐5p showed increased expression with more advanced tumor stage, while hsa‐miR‐200b‐3p, hsa‐miR‐215 and hsa‐miR‐451a had decreased expression with more advanced tumors. Thirteen miRNAs were associated with CRC mortality among individuals diagnosed with colon cancer while 14 were associated with CRC mortality after a diagnosis with rectal cancer. Strongest associations were observed for those miRNAs that were expressed in a small subset of tumors. Most notable associations were for hsa‐miR‐145‐3p [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.54, 5.61], and hsa‐miR‐9‐3p (HR 10.28, 95% CI 1.31, 80.84) with colon cancer and hsa‐miR‐335‐5p (HR 0.17, 95% CI 0.05, 0.54) for rectal cancer. hsa‐miR‐374a‐5p, hsa‐miR‐570‐3p and hsa‐miR‐18a‐5p significantly reduced the hazard of dying for all cases, regardless of tumor site. Our findings illustrate the need for a large sample to evaluate the association of miRNAs with survival and disease stage in order to determine associations by tumor site.
Ovarian cancer ascites enhance the migration of patient‐derived peritoneal mesothelial cells viacMet pathway through HGF‐dependent and ‐independent mechanisms
Authors: Matte Isabelle , Lane Denis , Laplante Claude , Garde‐Granger Perrine , Rancourt Claudine , Piché Alain
Published: December 2014

Ovarian cancer ascites consist of a proinflammatory environment that is characterized by the presence of abundant human peritoneal mesothelial cells (HPMCs). Cytokines and growth factors in ascites modulate cell activities of tumor cells. The expression of proinflammatory cytokines in ascites is associated with a more aggressive tumor phenotype. The effect of ascites on HPMCs is for the most part unknown but this interplay is thought to be important for epithelial ovarian cancer (EOC) progression. Here, we examine the components of ascites, which stimulate patient‐derived HPMC migration, from women with advanced EOC. We show that ovarian cancer ascites enhanced the migration of HPMCs. This effect was inhibited by heat treatment, hepatocyte growth factor (HGF) blocking antibodies and a HGF receptor (cMet) inhibitor. In ovarian cancer ascites, HGF is present at high concentration compared to benign fluids. Ascites‐mediated activation of cMet was associated with Akt and EKR1/2 phosphorylation. This response was partly inhibited by heat treatment and cMet inhibitor. Ascites‐induced migration and a cMet phosphorylation were strongly inhibited by epidermal growth factor receptor (EGFR) inhibitor PD153035, suggesting the transactivation of cMet by EGFR. Our study suggests that HGF and ligands of EGFR are factors that mediate ovarian cancer ascites‐mediated migration of HPMCs by activating cMet and possibly downstream ERK1/2 and Akt pathways. The study provides evidence for the first time that ascites not only support tumor growth but also enhance the migratory potential of cancer‐associated mesothelial cells, which in turn may support cancer progression.
Holographic imaging of unlabelled sperm cells for semen analysis: a review
Authors: Di Caprio Giuseppe , Ferrara Maria Antonietta , Miccio Lisa , Merola Francesco , Memmolo Pasquale , Ferraro Pietro , Coppola Giuseppe
Published: December 2014

Male reproductive health in both humans and animals is an important research field in biological study. In order to characterize the morphology, the motility and the concentration of the sperm cells, which are the most important parameters to feature them, digital holography demonstrated to be an attractive technique. Indeed, it is a label‐free, non‐invasive and high‐resolution method that enables the characterization of live specimen. The review is intended both for summarizing the state‐of‐art on the semen analysis and recent achievement obtained by means of digital holography and for exploring new possible applications of digital holography in this field.

Quantitative phase maps of living swimming spermatozoa.

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Quantitative phase maps of living swimming spermatozoa.