bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the tools of clinical pharmacology: Goals for 2017 and beyond
Authors: Zineh I , Abernethy D , Hop CECA , Bello A , McClellan MB , Daniel GW , Romine MH
Published: October 2016

Current trends in pronounced late‐stage attrition rates of promising drug candidates are a pressing concern for patients, providers, and other stakeholders across the health care system. Here, we describe six areas in which clinical pharmacology methods and frameworks can help ameliorate these trends in late‐stage attrition and increase the efficiency of drug development and evaluation. These recommendations are based, in part, on previous stakeholder engagement and input, as well as a previously published white paper.
Approaches, Challenges, and Advances in Metabolism of New Synthetic Cannabinoids and Identification of Optimal Urinary Marker Metabolites
Authors: Diao X , Huestis MA
Published: October 2016

We review approaches for determining metabolism of new synthetic cannabinoids (SCs), and challenges and advances in identifying optimal urinary marker metabolites of SC intake. Metabolic patterns of different SC generations are evaluated, and a practical strategy offered for selecting SC urinary marker metabolites. Novel SCs are incubated with human hepatocytes, the most abundant and characteristic metabolites are identified with high‐resolution mass spectrometry, and proposed hepatocyte marker metabolites are confirmed in authentic positive urine samples.
Elevated IL‐17A and IL‐22 regulate expression of inducible CD38 and Zap‐70 in chronic lymphocytic leukemia
Authors: Kouzegaran Samaneh , Siroosbakht Soheila , Farsad Bahram Fariborz , Rezakhaniha Bijan , Dormanesh Banafshe , Behnod Vahid , Tanha Amir Saber
Published: October 2016

Background

In this study, we investigated the role and expression of interleukin (IL)−17A and IL‐22 in chronic lymphocytic leukemia.

Methods

We evaluated the expression of markers above on CLL by ELISA, qRT‐PCR, flow cytometric analysis and nonparametric Kruskal–Wallis test.

Results

Quantitative RT‐PCR revealed that the mRNA levels of IL‐17A and IL‐22 in PBMCs of CLL patients were upregulated compared with those from healthy subjects (mean ± SD: 1.96 ± 0.232 vs.0.72 ± 0.15,P < 0.001 and mean ± SD: 2.45 ± 0.534 vs.0.81 ± 0.26,P < 0.001, respectivily). In addition, findings showed that the IL‐17A and IL‐22 plasma level was significantly elevated than that from healthy control group (P < 0.001). The median IL‐17A and IL‐22 in CLL patients and healthy control group were 48.28 ± 17.2 pg mL−1; 20.01 ± 11.16 pg mL−1and 58.68 ± 23.4 pg mL−1;16.47 ± 10.31P < 0.001, respectively. The levels of IL‐17A and IL‐22 was not significantly associated with the different stages of disease (Rai stages; Kruskal–Wallis testP > 0.05).No significant relationship was found between expression of CD38 and higher median serum levels of IL‐17A in patients, but patients with negative expression of ZAP‐70 showed a significant association with higher median serum levels of IL‐17A compared with healthy subjects. (57.84 pg mL−1vs. 31.67 pg mL−1;P = 0.016).

Conclusion

IL‐22 is elevated and associated with CD38 and Zap‐70 expression in patients with CLL. No significant correlation was found between expression of CD38 and increased levels of IL‐17A, negative expression of ZAP‐70 showed a significant association with increased levels of IL‐17A. © 2016 International Clinical Cytometry Society
Pubertal pair‐housing facilitates adult sexual behavior in male rats
Authors: Molenda‐Figueira Heather A. , Bell Margaret R. , De Lorme Kayla C. , Sisk Cheryl L.
Published: October 2016

This study examined the effects of pubertal testosterone (T) and social housing manipulations on male sexual behavior in adult rats. Prepubertal rats were castrated at 21 days of age (P21) and implanted with either blank or T‐releasing pellets. At the onset of puberty, P28, half the rats in each treatment group were either single‐ or pair‐housed with a male of the same hormone condition through P56, at which time pellets were removed and all rats were single‐housed. In adulthood (P84), all rats received T replacement and were tested for sexual behavior. Rats pair‐housed during adolescence showed more sexual behavior and greater improvement of sexual performance over repeated tests than single‐housed rats, regardless of pubertal T status. Pubertal T, however, did facilitate the frequency of anogenital investigation. Thus, in male rats, social interactions during adolescence are more important than exposure to pubertal T in enhancing adult sexual behavior.
Selective androgen receptor modulators: comparative excretion study of bicalutamide in bovine urine and faeces
Authors: Rojas Dante , Dervilly‐Pinel Gaud , Cesbron Nora , Penot Mylène , Sydor Alexandre , Prévost Stéphanie , Le Bizec Bruno
Published: October 2016

Besides their development for therapeutic purposes, non‐steroidal selective androgen receptor modulators (non‐steroidal SARMs) are also known to impact growth‐associated pathways as ligands of androgenic receptors (AR). They present a potential for abuse in sports and food‐producing animals as an interesting alternative to anabolic androgenic steroids (AAS). These compounds are easily available and could therefore be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies should be developed for specific and sensitive detection of these compounds in biological matrices. The present study focused on Bicalutamide, a non‐steroidal SARM used in human treatment of non‐metastatic prostate cancer because of its anti‐androgenic activity exhibiting no anti‐anabolic effects. To select the most appropriate matrix to be used for control purposes, different animal matrices (urine and faeces) have been investigated and SARM metabolism studied to highlight relevant metabolites of such treatments and establish associated detection time windows. The aim of this work was thus to compare the urinary and faecal eliminations of bicalutamide in a calf, and investigate phase I and II metabolites. The results in both matrices showed that bicalutamide was very rapidly and mainly excreted under its free form. The concentration levels were observed as higher in faeces (ppm) than urine (ppb); although both matrices were assessed as suitable for residue control. The metabolites found were consistent with hydroxylation (phase I reaction) combined or not with glucuronidation and sulfation (phase II reactions). Copyright © 2016 John Wiley & Sons, Ltd.
Assessing cannabis consumption frequency: Is the combined use of free and glucuronidated THCCOOH blood levels of diagnostic utility?
Authors: Hädener Marianne , Martin Fabritius Marie , König Stefan , Giroud Christian , Weinmann Wolfgang
Published: October 2016

Heavy cannabis consumption is considered incompatible with safe driving. In Swiss traffic policy, drivers suspected of regular cannabis use are therefore required to undergo medical assessment of their long‐term fitness to drive. A whole blood concentration of the cannabis metabolite 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THCCOOH) of 40 µg/L is currently used by Swiss forensic experts as the decision limit for regular cannabis consumption. The present study aimed to investigate the suitability of THCCOOH‐glucuronide blood levels as an additional and/or better marker for the frequency of cannabis use. Whole blood samples collected from 23 heavy (≥10 joints/month) and 25 occasional smokers (≥1 joint/month, but ≤ 1 joint/week) enrolled in a placebo‐controlled cannabis smoking study were analyzed for THCCOOH and THCCOOH‐glucuronide. Based on receiver operating characteristic (ROC) curve analysis, concentration thresholds could be established for distinguishing between these two groups. Proposed thresholds for heavy use were THCCOOH‐glucuronide > 52 µg/L (100% specificity; 41% sensitivity) and/or total THCCOOH > 58 µg/L (100% specificity; 43% sensitivity). Optimum thresholds for occasional use were THCCOOH‐glucuronide < 5 µg/L (73% specificity; 97% sensitivity) and/or total THCCOOH < 5 µg/L (62% specificity; 98% sensitivity). Our results indicate that the THCCOOH‐glucuronide whole blood concentration is a useful parameter that complements the free THCCOOH level to assess the frequency of cannabis consumption. The consideration of the blood concentrations of both free and glucuronidated THCCOOH improves the identification of heavy users whose fitness to drive has to be carefully assessed. Copyright © 2016 John Wiley & Sons, Ltd.
Generation of a NK1R‐CreER knockin mouse strain to study cells involved in Neurokinin 1 Receptor signaling
Authors: Huang Huizhen , Kuzirian Marissa S. , Cai Xiaoyun , Snyder Lindsey M. , Cohen Jonathan , Kaplan Daniel H. , Ross Sarah E.
Published: October 2016

The Neurokinin 1 Receptor (NK1R), which binds Substance P, is expressed in discrete populations of neurons throughout the nervous system, where it has numerous roles including the modulation of pain and affective behaviors. Here, we report the generation of a NK1R‐CreER knockin allele, in which CreERT2 replaces the coding sequence of the TACR1 gene (encoding NK1R) in order to gain genetic access to these cells. We find that the NK1R‐CreER allele mediates recombination in many regions of the nervous system that are important in pain and anxiety including the amygdala, hypothalamus, frontal cortex, raphe nucleus, and dorsal horn of the spinal cord. Other cell types that are labeled by this allele include amacrine cells in the retina and fibroblasts in the skin. Thus, the NK1R‐CreER mouse line is a valuable new tool for conditional gene manipulation enabling the visualization and manipulation of cells that express NK1R.
Inducible gene modification in the gastric epithelium of Tff1‐CreERT2, Tff2‐rtTA, Tff3‐luc mice
Authors: Thiem Stefan , Eissmann Moritz F. , Stuart Emma , Elzer Joachim , Jonas Anna , Buchert Michael , Ernst Matthias
Published: October 2016

Temporal and spatial regulation of genes mediated by tissue‐specific promoters and conditional gene expression systems provide a powerful tool to study gene function in health, disease, and during development. Although transgenic mice expressing the Cre recombinase in the gastric epithelium have been reported, there is a lack of models that allow inducible and reversible gene modification in the stomach. Here, we exploited the gastrointestinal epithelium‐specific expression pattern of the three trefoil factor (Tff) genes and bacterial artificial chromosome transgenesis to generate a novel mouse strain that expresses the CreERT2 recombinase and the reverse tetracycline transactivator (rtTA). The Tg(Tff1‐CreERT2;Tff2‐rtTA;Tff3‐Luc) strain confers tamoxifen‐inducible irreversible somatic recombination and allows simultaneous doxycycline‐dependent reversible gene activation in the gastric epithelium of developing and adult mice. This strain also confers luciferase activity to the intestinal epithelium to enable in vivo bioluminescence imaging. Using fluorescent reporters as conditional alleles, we show Tff1‐CreERT2 and Tff2‐rtTA transgene activity in a partially overlapping subset of long‐term regenerating gastric stem/progenitor cells. Therefore, the Tg(Tff1‐CreERT2;Tff2‐rtTA;Tff3‐Luc) strain can confer intermittent transgene expression to gastric epithelial cells that have undergone previous gene modification, and may be suitable to genetically model therapeutic intervention during development, tumorigenesis, and other genetically tractable diseases. Birth Defects Research (Part A) 106:626–635, 2016. © 2016 Wiley Periodicals, Inc.
Carbon cycling in temperate grassland under elevated temperature
Authors: Jansen‐Willems Anne B. , Lanigan Gary J. , Grünhage Ludger , Müller Christoph
Published: October 2016

An increase in mean soil surface temperature has been observed over the last century, and it is predicted to further increase in the future. The effect of increased temperature on ecosystem carbon fluxes in a permanent temperate grassland was studied in a long‐term (6 years) field experiment, using multiple temperature increments induced by IR lamps. Ecosystem respiration (R‐eco) and net ecosystem exchange (NEE) were measured and modeled by a modified Lloyd and Taylor model including a soil moisture component for R‐eco (average R2 of 0.78) and inclusion of a photosynthetic component based on temperature and radiation for NEE (R2 = 0.65). Modeled NEE values ranged between 2.3 and 5.3 kg CO2 m−2 year−1, depending on treatment. An increase of 2 or 3°C led to increased carbon losses, lowering the carbon storage potential by around 4 tonnes of C ha−1 year−1. The majority of significant NEE differences were found during night‐time compared to daytime. This suggests that during daytime the increased respiration could be offset by an increase in photosynthetic uptake. This was also supported by differences in δ13C and δ18O, indicating prolonged increased photosynthetic activity associated with the higher temperature treatments. However, this increase in photosynthesis was insufficient to counteract the 24 h increase in respiration, explaining the higher CO2 emissions due to elevated temperature.
Cascading effects of N input on tritrophic (plant–aphid–parasitoid) interactions
Authors: Chesnais Quentin , Couty Aude , Catterou Manuella , Ameline Arnaud
Published: October 2016

Because N is frequently the most limiting mineral macronutrient for plants in terrestrial ecosystems, modulating N input may have ecological consequences through trophic levels. Thus, in agro‐ecosystems, the success of natural enemies may depend not only from their herbivorous hosts but also from the host plant whose qualities may be modulated by N input. We manipulated foliar N concentrations by providing to Camelina sativa plants three different nitrogen rates (control, optimal, and excessive). We examined how the altered host‐plant nutritional quality influenced the performances of two aphid species, the generalist green peach aphid, Myzus persicae, and the specialist cabbage aphid, Brevicoryne brassicae, and their common parasitoid Diaeretiella rapae. Both N inputs led to increased N concentrations in the plants but induced contrasted concentrations within aphid bodies depending on the species. Compared to the control, plant biomass increased when receiving the optimal N treatment but decreased under the excessive treatment. Performances of M. persicae improved under the optimal treatment compared to the control and excessive treatments whereas B. brassicae parameters declined following the excessive N treatment. In no‐choice trials, emergence rates of D. rapae developing in M. persicae were higher on both optimum and excessive N treatments, whereas they remained stable whatever the treatment when developing in B. brassicae. Size of emerging D. rapae females was positively affected by the treatment only when it developed in M. persicae on the excessive N treatment. This work showed that contrary to an optimal N treatment, when N was delivered in excess, plant suitability was reduced and consequently affected negatively aphid parameters. Surprisingly, these negative effects resulted in no or positive consequences on parasitoid parameters, suggesting a buffered effect at the third trophic level. Host N content, host suitability, and dietary specialization appear to be major factors explaining the functioning of our studied system.
A whole‐plant perspective reveals unexpected impacts of above‐ and belowground herbivores on plant growth and defense
Authors: Mundim Fabiane M. , Alborn Hans T. , Vieira‐Neto Ernane H. M. , Bruna Emilio M.
Published: October 2016

Trade‐offs between plant growth and defense are central to theoretical frameworks used to study the ecology and evolution of plant defense against herbivores. However, these frameworks, as well as the experiments designed to test them, rarely include belowground herbivores. We experimentally challenged seedlings of the tropical shrub Solanum lycocarpum (Solanaceae) with either aboveground foliar herbivores (Spodoptera caterpillars) or belowground root herbivores (the nematode Meloidogyne incognita) and measured the resulting changes in plant growth rates, biomass allocation, and the concentration of defensive terpenoids in roots and leaves. We found that plants that suffered aboveground herbivory responded with aboveground growth but belowground defense. Similarly, belowground herbivory resulted in root growth but elevated defenses of leaves. These results underscore the importance of belowground plant–herbivore interactions, and suggest that, in contrast to theoretical predictions, plants can simultaneously invest in both growth and defense. Finally, they emphasize the need for a “whole‐plant” perspective in theoretical and empirical evaluations of plant–herbivore interactions.
The soluble cytoplasmic tail of CD45 (ct‐CD45) in human plasma contributes to keep T cells in a quiescent state
Authors: Puck Alexander , Hopf Stefan , Modak Madhura , Majdic Otto , Cejka Petra , Blüml Stephan , Schmetterer Klaus , Arnold‐Schrauf Catharina , Gerwien Jens G. , Frederiksen Klaus S. , Thell Elisabeth , Leitner Judith , Steinberger Peter , Aigner Regina , Seyerl‐Jiresch Maria , Zlabinger Gerhard J. , Stöckl Johannes
Published: October 2016

The cytoplasmic tail of CD45 (ct‐CD45) is proteolytically cleaved and released upon activation of human phagocytes. It acts on T cells as an inhibitory, cytokine‐like factor in vitro. Here, we show that ct‐CD45 is abundant in human peripheral blood plasma from healthy adults compared with plasma derived from umbilical cord blood and plasma from patients with rheumatoid arthritis or systemic lupus erythematosus. Plasma depleted of ct‐CD45 enhanced T‐cell proliferation, while addition of exogenous ct‐CD45 protein inhibited proliferation and reduced cytokine production of human T lymphocytes in response to TCR signaling. Inhibition of T‐cell proliferation by ct‐CD45 was overcome by costimulation via CD28. T‐cell activation in the presence of ct‐CD45 was associated with an upregulation of the quiescence factors Schlafen family member 12 (SLFN12) and Krueppel‐like factor 2 (KLF2) as well as of the cyclin‐dependent kinase (CDK) inhibitor p27kip1. In contrast, positive regulators of the cell cycle such as cyclin D2 and D3 as well as CDK2 and CDK4 were found to be downregulated in response to ct‐CD45. In summary, we demonstrate that ct‐CD45 is present in human plasma and sets the threshold of T‐cell activation.
IL4I1: Key immunoregulator at a crossroads of divergent T‐cell functions
Authors: Romagnani Sergio
Published: October 2016

The interleukin (IL)‐4‐induced gene1 (IL4I1), which encodes the L‐amino acid oxidase enzyme, plays an important immunoregulatory role. Indeed, this enzyme which is produced by B cells—including neoplastic B cells—dendritic cells and macrophages has been shown to inhibit proliferation, cytotoxicity and IFN‐γ production by tumor‐infiltrating CD8+ T cells, thus favoring tumor escape. Moreover, the same gene has been found to be constitutively expressed by CD4+ T helper 17 (Th17) cells, where it down‐regulates cell proliferation through a reduction of CD3 chains expression in the T‐cell receptor complex, thus impairing IL‐2 production, and by maintaining in the same cells a high expression of Tob1, which inhibits cell cycle entry, through a still unknown mechanism. Finally, IL4I1 has been shown to drive the differentiation of naive T cells into inducible regulatory T (iTreg) cells. Taken together, IL4I1 down‐regulates the effector CD8+ T‐cell response, promotes the development of iTreg cells and limits the expansion of Th17 cells, thus not only favoring tumor escape, but also reducing the potentially dangerous effects of adaptive immune responses in chronic inflammatory disorders.
Helicity in Photocatalysis – Advantage or Obstacle? Studies on Silver Complexes – Synthesis, Structure, and Photocatalytic Activity
Authors: Fik Marta A. , Kubicki Maciej , Odachowska Angelika E. , Karpińska Joanna , Patroniak Violetta
Published: October 2016

Much attention has been focused recently on the improvement of the photocatalytic efficiencies of known degradation catalysts and the design of new ones. As silver(I) compounds are of high interest in the field of photodegradation owing to their good optical and electron properties concerning their HOMO–LUMO (HOMO = highest occupied molecular orbital, LUMO = lowest unoccupied molecular orbital) band gaps, we have synthesized two new complexes with a Schiff base type ligand (L) of formulas [AgL(OTf)] (OTf = triflate) and [Ag2L2][PF6]2 (monomeric and helical, respectively). In this study, we have shown that the mono‐ and dinuclear species are both capable of consuming the organic waste in water; however, the monomeric complex [AgL(OTf)] is more active towards the degradation of the model compounds methylene blue (MB) and quinoline yellow (QY) owing to the lability of one of its coordination site. At the same time, the AgI ions in the helical complex [Ag2L2][PF6]2 are hindered in a cavity formed by the two ligands wrapped around them, and this slightly inactivates the complex. However, the helical complex is recyclable, whereas [AgL(OTf)] decomposes after one cycle of irradiation.
2‐[(1E,3E)‐4‐Arylbuta‐1,3‐dien‐1‐yl]‐4H‐chromen‐4‐ones as Dienes in Diels–Alder Reactions – Experimental and Computational Studies
Authors: Albuquerque Hélio M. T. , Santos Clementina M. M. , Lima Carlos F. R. A. C. , Santos Luís M. N. B. F. , Cavaleiro José A. S. , Silva Artur M. S.
Published: October 2016

The synthesis and reactivity of 2‐[(1E,3E)‐4‐arylbuta‐1,3‐dien‐1‐yl]‐4H‐chromen‐4‐ones as dienes in Diels–Alder (DA) reactions with several electron‐poor and electron‐rich dienophiles under microwave irradiation was studied. The optimized reaction conditions were achieved with N‐methylmaleimide as the dienophile and Sc(OTf)3 (OTf = triflate) as a Lewis acid under microwave‐assisted and solvent‐free conditions. The Lewis acid improved the reaction yields as it prevented the adducts obtained from undergoing a second DA reaction; thus, the formation of a bisadduct was avoided. The α,β:γ,δ‐diene of the starting chromones was the most reactive, and the computational results confirmed the experimental findings. Theoretical calculations also provided a rationale for the unexpected lack of reactivity shown by some dienophiles. The adducts prepared were dehydrogenated with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ); however, the aza adducts were sensitive to the highly energetic reaction conditions necessary for the aromatization.
Randomized sham‐controlled, double‐blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain
Authors: van Tilburg C.W.J. , Stronks D.L. , Groeneweg J.G. , Huygen F.J.P.M.
Published: October 2016

Background

Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain.

Methods

Randomized sham‐controlled, double‐blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0–10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. Primary outcome measure: pain reduction. Secondary outcome measure: Global Perceived Effect.

Results

No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found.

Conclusions

The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction.

Significance

Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham‐controlled, double‐blind, multicenter clinical trial on the effect of radiofrequency at the ramus communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected.
Effects of CNT‐film Pretreatment on the Characteristics of NiCo2O4/CNT Core‐shell Hybrids as Electrode Material for Electrochemistry Capacitor
Authors: Geng Ling , Xu Shanshan , Liu Jiachen , Guo Anran , Hou Feng
Published: October 2016

NiCo2O4/CNT nanocomposite films were fabricated by in‐situ growing ultrafine NiCo2O4 nanoparticles on acid‐modified carbon nanotube (CNT) films. The effects of CNT‐film pretreatment were investigated thoroughly by various characterization outfits including Fourier Transform Infrared spectroscopy (FT‐IR), X‐ray photoelectron spectroscopy (XPS), Raman spectroscopy, RTS‐9 four‐point probes resistivity measurement system, X‐ray powder diffraction (XRD), scanning electron microscopy (SEM) and CHI660D electrochemical workstation. These results suggested that carbon nanotubes were uniformly wrapped by NiCo2O4 nanoparticles forming a hierarchical core‐shell structure. And the crystallinity, conductivity of the CNTs and detail structure (both morphology and size) of the NiCo2O4 nanoparticles varied with prolonged acid treatment time which resulted in increased functional groups and defects on CNT films and further affected the electrochemical properties. The composite film composed of the CNT film pretreated by mixed acid for 12 h exhibited excellent electrochemical properties: 828 F/g at 1 A/g and 656 F/g at 20 A/g, and maintained over 99 % of its capacitance after 3000 cycles of charge/discharge at 5 A/g. Acid treatment for either too long or too short is detrimental to the electrochemical properties of the composite films. Such work should be of fundamental importance for tailoring electrochemical properties by elaborate design of acid treatment on CNTs.
Electrochemical (Bio)sensing of Clinical Markers Using Quantum Dots
Authors: Pedrero María , Campuzano Susana , Pingarrón José M.
Published: October 2016

Quantum dots (QDs) are a kind of semiconductor nanoparticles with great potential in (bio)sensing for medical diagnosis due not only to their optical properties but also to their applicability in the development of electrochemical (bio)sensors. In this article, the use of metallic and graphene QDs for electrochemical signal amplification, either as signal tags or as electrode surface modifiers to detect clinical markers is reviewed and critically discussed. The advantages and disadvantages arising from the use of these nanoparticles in this context will be outlined together with the still required work to fulfil the characteristics needed to attain suitable electrochemical (bio)sensors with real application in clinical field.
Polar and nonpolar organic polymer‐based monolithic columns for capillary electrochromatography and high‐performance liquid chromatography
Authors: Rathnasekara Renuka , Khadka Shantipriya , Jonnada Murthy , El Rassi Ziad
Published: October 2016

This review article is a continuation of the previous reviews on the area of monolithic columns covering the progress made in the field over the last couple of years from the beginning of the second half of 2014 until the end of the first half of 2016. It summarizes and evaluates the evolvement of both polar and nonpolar organic monolithic columns and their use in hydrophilic interaction LC and CEC and reversed‐phase chromatography and RP‐CEC. The review article discusses the results reported in a total of 62 references.
Combustion‐Generated Noise: An Environment‐Related Issue for Future Combustion Systems
Authors: Zhang Feichi , Zirwes Thorsten , Nawroth Holger , Habisreuther Peter , Bockhorn Henning , Paschereit Christian Oliver
Published: October 2016

A first‐order estimation of the prediction of combustion‐generated noise from turbulent premixed flames was explored. The method was based on Lighthill's acoustic analogy and used measurement data from high‐speed imaging of chemiluminescent emissions as input. To determine the noise‐generating source, that is, the overall heat release rate from the measured chemiluminescence signals, numerical simulations were performed for 1 D laminar and 3 D turbulent freely propagating flames by employing detailed transport models and reaction mechanisms, including the full reaction chain of the electronically excited hydroxyl radical (OH*). It was shown for both the 1 D and 3 D cases that the local generation of OH* correlated strongly with the heat released from the chemical reaction, especially in the fuel‐lean range. As the chemiluminescence measurements gathered light only along the viewing direction, the line‐of‐sight summed values of heat release rate and OH* concentration were evaluated from the 3 D simulation, and a quasilinear relationship was identified for these integral values. Hence, a proportionality relation was applied for computation of the integral heat release from measured chemiluminescence intensity. An analytical solution of Lighthill's wave equation served as a transfer function, which took fluctuations in the total heat release rate or light intensity as input to calculate the sound radiation in the far field. This approach was applied to a generic burner operated with premixed methane/air jet flames. Good quantitative agreement was obtained between the sound pressures derived from the chemiluminescence measurements and the microphone data, which highlights the potential of the method for applications to more complex flame configurations.
Dissipation of double-stranded RNA in aquatic microcosms
Authors: Albright Vurtice C. , Wong Colin R. , Hellmich Richard L. , Coats Joel R.
Published: October 2016

Silencing genes of a pest with double-stranded RNA (dsRNA) is a promising new pest management technology. As part of the environmental risk assessment for dsRNA-based products, the environmental fate and the potential for adverse effects to on-target organisms should be characterized. In the present study, a nonbioactive dsRNA was spiked into the water column of a water and sediment microcosm to mimic drift from a spray application run off of unbound dsRNA or transport of plant tissues. Dissipation of dsRNA in the water column and partitioning into sediment was determined. The dsRNA rapidly dissipated in the water column and was below the limit of detection after 96 h. The levels detected in the sediment were not significant and may indicate rapid degradation in the water column prior to partitioning to sediment. Environ Toxicol Chem 2017;36:1249–1253. © 2016 SETAC
Functional traits of urban trees: air pollution mitigation potential
Authors: Grote Rüdiger , Samson Roeland , Alonso Rocío , Amorim Jorge Humberto , Cariñanos Paloma , Churkina Galina , Fares Silvano , Thiec Didier Le , Niinemets Ülo , Mikkelsen Teis Norgaard , Paoletti Elena , Tiwary Abhishek , Calfapietra Carlo
Published: October 2016

In an increasingly urbanized world, air pollution mitigation is considered one of most important issues in city planning. Urban trees help to improve air quality by facilitating widespread deposition of various gases and particles through the provision of large surface areas as well as through their influence on microclimate and air turbulence. However, many of these trees produce wind‐dispersed pollen (a known allergen) and emit a range of gaseous substances that take part in photochemical reactions – all of which can negatively affect air quality. The degree to which these air‐quality impacts are manifested depends on species‐specific tree properties: that is, their “traits”. We summarize and discuss the current knowledge on how such traits affect urban air pollution. We also present aggregated traits of some of the most common tree species in Europe, which can be used as a decision‐support tool for city planning and for improving urban air‐quality models.
Influence of low dose of gamma radiation and storage on some vitamins and mineral elements of dried oyster mushrooms (Pleurotus ostreatus)
Authors: Kortei Nii Korley , Odamtten George Tawia , Obodai Mary , Wiafe‐Kwagyan Michael , Addo Edward Adotey
Published: October 2016

Mushrooms contain some of the most potent natural medicines on the planet. Vitamins A, C, D, Mineral elements, contents, as well as total soluble solids (Brixo) of dried composition of Pleurotus ostreatus were investigated after exposing to gamma radiation doses of 0 (control), 0.5, 1, 1.5, and 2 kGy at a dose rate of 1.7 kGy per hour in air from a Cobalt 60 source (SLL 515, Hungary) batch irradiator prior to storage (0 month) and after storage (12 months) at room temperature (28 ± 2°C). Results obtained showed some significant (p < .05) differences due to irradiation and storage. Before storage, vitamins A, C, and D contents of dried and irradiated mushrooms ranged 0.003 ± 0.08–0.014 ± 0.08, 0.042 ± 1.06–0.132 ± 1.06, and 0.040 ± 0.76–0.057 ± 0.76 mg/g, respectively. After 12 months, vitamin contents decreased and ranged 0.0029 ± 0.08–0.010 ± 0.08, 0.038 ± 1.06–0.125 ± 1.06, and 0.031 ± 0.76–0.05 ± 0.76 mg/g for vitamins A, C, and D, respectively. Total soluble solids recorded 1.5 Brixo, however, showed no significant difference (p > .05) and did not change in 12 months after gamma irradiation up to 2 kGy. Sodium ranged from 14.00 ± 0.7 to 14.90 ± 0.8 mg/100 g. Potassium content varied from 30.20 ± 0.5 to 33.10 ± 0.6 mg/100 g. Magnesium content ranged 1.27 ± 0.15–3.53 ± 0.04 mg/100 g. Calcium ranged 11.00 ± 0.4–12.53 ± 0.4 ± 0.03 mg/100 g. Phosphorus content ranged 6.11 ± 0.30–6.41 ± 0.35 mg/100 g, whereas Nitrogen content was found to be 3.00 ± 0.03–3.60 ± 0.25 mg/100 g. Microelements or heavy metals included Copper; detected ranged 0.00 ± 0.00–0.02 ± 0.001 mg/100 g, Zinc content ranged 0.01 ± 0.002–0.03 ± 0.001 mg/100 g. Iron content was found to be in the range 0.29 ± 0.01–0.37 ± 0.1 mg/100 g. Manganese content was found to be in the range 0.03 ± 0.001–0.04 ± 0.01 mg/100 g. Lead content was found to be 0.00 ± 0.00–0.03 ± 0.001 mg/100 g. Food processing and storage has the potential to slightly alter the stability of vitamins in foods. Pleurotus ostreatus showed appreciable levels of mineral elemental composition, essential vitamins A, C, and D, and can be endorsed as a natural medicinal food product in the food and pharmaceutical industries. The heavy metals detected were with also below the upper limits permissible by the WHO standards and is thus safe for human consumption.
Germline BAP1 alterations in familial uveal melanoma
Authors: Rai Karan , Pilarski Robert , Boru Getachew , Rehman Muneeb , Saqr Ahmad H. , Massengill James B. , Singh Arun , Marino Meghan J. , Davidorf Frederick H. , Cebulla Colleen M. , H. Abdel‐Rahman Mohamed
Published: October 2016

Uveal melanoma (UM) is the most commonly diagnosed primary intraocular tumor in adults. Familial UM (FUM), defined as two or more family members diagnosed with UM, is rare and estimated at less than 1% of all UM. Currently, BAP1 is the only gene known to contribute significant risk for UM. In this study we aimed to estimate the frequency of BAP1 mutation in FUM and to characterize the family and personal histories of other cancers in these families. We identified 32 families with FUM, including seven families previously reported by our group. BAP1 mutation testing was carried out by direct sequencing of the coding exons and the adjacent untranslated regions of the gene. Germline deletion and duplication analysis of BAP1 was assessed by multiplex ligation‐dependent probe amplification (MLPA). Germline BAP1 mutations were found in 6/32 (19%) families. No deletions or duplications were identified in any of the 24 samples tested by MLPA. Combined with published studies, the frequency of BAP1 mutations was 14/64 (22%) in FUM. FUM families without BAP1 mutations have distinct family histories with high rates of prostate cancer in first‐ and second‐degree relatives. It is likely that additional genes conferring risk for FUM exist. It is important to understand key shared features of FUM to focus future research on identifying these additional tumor predisposition syndromes. Though BAP1 should be tested first in these families, FUM families without BAP1 mutation should be explored for additional predisposition genes. © 2016 Wiley Periodicals, Inc.
Critical role of Ror2 receptor tyrosine kinase in regulating cell cycle progression of reactive astrocytes following brain injury
Authors: Endo Mitsuharu , Ubulkasim Guljahan , Kobayashi Chiho , Onishi Reiko , Aiba Atsu , Minami Yasuhiro
Published: October 2016

Ror2 receptor tyrosine kinase plays crucial roles in developmental morphogenesis and tissue‐/organo‐genesis. In the developing brain, Ror2 is expressed in neural stem/progenitor cells (NPCs) and involved in the regulation of their stemness. However, it remains largely unknown about its role in the adult brain. In this study, we show that Ror2 is up‐regulated in reactive astrocytes in the neocortices within 3 days following stab‐wound injury. Intriguingly, Ror2‐expressing astrocytes were detected primarily at the area surrounding the injury site, where astrocytes express Nestin, a marker of NPCs, and proliferate in response to injury. Furthermore, we show by using astrocyte‐specific Ror2 knockout (KO) mice that a loss of Ror2 in astrocytes attenuates injury‐induced proliferation of reactive astrocytes. It was also found that basic fibroblast growth factor (bFGF) is strongly up‐regulated at 1 day post injury in the neocortices, and that stimulation of cultured quiescent astrocytes with bFGF restarts their cell cycle and induces expression of Ror2 during the G1 phase predominantly in proliferating cells. By using this culture method, we further show that the proportions of Ror2‐expressing astrocytes increase following treatment with the histone deacetylases inhibitors including valproic acid, and that bFGF stimulation increases the levels of Ror2 expression within the respective cells. Moreover, we show that bFGF‐induced cell cycle progression into S phase is inhibited or promoted in astrocytes from Ror2 KO mice or NPCs stably expressing Ror2‐GFP, respectively. Collectively, these findings indicate that Ror2 plays a critical role in regulating the cell cycle progression of reactive astrocytes following brain injury, GLIA 2016. GLIA 2017;65:182–197
Psychosocial or clinico‐demographic factors related to neuropsychiatric symptoms in patients with Alzheimer's disease needing interventional treatment: analysis of the CATIE‐AD study
Authors: Nagata Tomoyuki , Nakajima Shinichiro , Shinagawa Shunichiro , Plitman Eric , Graff‐Guerrero Ariel , Mimura Masaru , Nakayama Kazuhiko
Published: October 2016

Objective

This study sought to determine psychosocial and clinico‐demographic factors related to each symptomatic cluster (i.e., aggressiveness, psychosis, apathy/eating problems, and emotion/disinhibition) of neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) needing interventional treatment against their agitation or psychotic symptoms. These clusters were classified from 12 Neuropsychiatric Inventory (NPI) subscores in our previous study using the Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer's Disease (CATIE‐AD) dataset.

Methods

Based on clinical data from 421 AD outpatients with agitation or psychotic symptoms needed interventional treatment enrolled in the CATIE‐AD, we conducted logistic regression analyses to examine the relationships between each symptomatic cluster and three psychosocial (marital status, residence, and caregivers' burden) and nine clinico‐demographic (age, gender, education year, general cognition, activity of daily living [ADL], general medical health, race, and intake of anti‐dementia drugs or psychotropics) factors.

Results

While no factor contributed to aggressiveness, psychosis was associated with several clinico‐demographic factors: female gender, non‐Caucasian race, and lower cognitive function. Apathy/eating problems was associated with more severe caregiver burden, living in one's own home, lower ADL level, and male gender, while emotion/disinhibition was predicted by more severe caregiver burden, lower education level, not‐married status, and younger age.

Conclusions

Among the four NPS clusters, apathy/eating problems and emotion/disinhibition were associated with psychosocial as well as clinico‐demographic factors in AD patients with psychotic symptoms or agitation needed interventional treatment. Copyright © 2016 John Wiley & Sons, Ltd.
Li–Fraumeni syndrome presenting as mucosal melanoma: Case report and treatment considerations
Authors: Klein Jonah D. , Kupferman Michael E.
Published: October 2016

Background

Li–Fraumeni syndrome (LFS) is a familial cancer predisposition associated with a germline mutation in TP53. Patients with LFS are at risk of developing malignancies and require comprehensive screening. We describe an index case of LFS presenting with mucosal melanoma.

Methods

A 21‐year‐old woman presented with a left maxillary mucosal lesion and a left neck mass. Biopsies revealed metastatic mucosal melanoma, which is a pathology previously unreported in LFS families. Genetic testing revealed LFS, with a germline TP53 mutation, and pedigree analysis identified 9 first‐degree and second‐degree relatives with hematologic malignancies.

Results

The patient underwent a maxillectomy and left neck dissection, followed by adjuvant radiotherapy. At 30‐month follow‐up, there was no evidence of local, regional, or distant failure, nor did she develop a second primary tumor.

Conclusion

This represents the first reported case of LFS associated with mucosal melanoma. Treatment considerations, specifically the risks of adjuvant therapy in LFS, are discussed. © 2016 Wiley Periodicals, Inc. Head Neck 39: E20–E22, 2017
Clinical impact of 18F‐FDG positron emission tomography/CT on adenoid cystic carcinoma of the head and neck
Authors: Jung Ji‐hoon , Lee Sang‐Woo , Son Seung Hyun , Kim Choon‐Young , Lee Chang‐Hee , Jeong Ju Hye , Jeong Shin Young , Ahn Byeong‐Cheol , Lee Jaetae
Published: October 2016

Background

The purpose of this retrospective study was to assess the diagnostic value of 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and the prognostic value of metabolic PET parameters in patients with adenoid cystic carcinoma of the head and neck (ACCHN).

Methods

Forty patients with newly diagnosed ACCHN were enrolled in this study. We investigated the diagnostic value of 18F‐FDG PET/CT for detecting and staging compared to conventional CT. Kaplan–Meier survival analysis for progression‐free survival (PFS) was performed with clinicopathological factors and metabolic PET parameters.

Results

The 18F‐FDG PET/CT showed comparable sensitivity (92.3%) to conventional CT for lesion detection, and changed staging and management plan in 6 patients (15.0%). Lower PFS rates were associated with advanced T classification, advanced TNM classification, high maximum standardized uptake value (SUVmax; >5.1), and high total lesion glycolysis (>40.1) of the primary tumor.

Conclusion

The 18F‐FDG PET/CT can provide additional information for initial staging, and metabolic PET parameters may serve as prognostic factors of ACCHN. © 2016 Wiley Periodicals, Inc. Head Neck 39: 447–455, 2017
On‐Surface Metalation and 2D Self‐Assembly of Pyrphyrin Molecules Into Metal‐Coordinated Networks on Cu(111)
Authors: Li Jingyi , Wäckerlin Christian , Schnidrig Stephan , Joliat Evelyne , Alberto Roger , Ernst Karl‐Heinz
Published: October 2016

The metalation of the tetradentate molecule pyrphyrin by copper substrate atoms on a Cu(111) surface is studied. Pyrphyrin, in contrast to porphyrin, consists of four fused pyridine groups instead of pyrrol groups. Using thermal desorption spectroscopy (TDS) and N 1s X‐ray photoelectron spectroscopy (XPS), we show that metalation of the monolayer of pyrphyrin with Cu atoms from the Cu(111) surface occurs at 377 K. The formation of an extended two‐dimensional (2D) network is observed with scanning tunneling microscopy (STM). A honeycomb‐like lattice of metalated pyrphyrin molecules is formed by intermolecular connection via the two cyano groups at the periphery of pyrphyrin as well as Cu adatoms. Dehydrogenation at the periphery of the molecule is observed during annealing at 520 K. The surface‐adsorbed metal‐pyrphyrin has the potential to serve as a molecular catalyst.
Growing concerns and controversies to Taiwan's National Health Insurance—what are the lessons from mainland China, South Korea and Singapore?
Authors: Lee Yen‐Han , Ang Ting Fang Alvin , Chiang Timothy C. , Kaplan Warren A.
Published: October 2016

It has been over 20 years since Taiwan's implementation of its National Health Insurance (NHI) program. Under this program, the health insurance coverage rate has reached approximately 99% of the population. Despite guaranteeing the residents of Taiwan equal access regardless of socioeconomic status and background, critical problems and controversies persist, and they continue to challenge the NHI. We analyze the primary issues facing the NHI program with emphasis on financial and consumer behavioral aspects. Furthermore, we apply models from mainland China, South Korea and Singapore to discuss what Taiwan could learn from the systems employed by these countries to modify the NHI. Targeting the needs of the NHI, we have three policy recommendations: separating the NHI scheme into different target populations, strengthening the NHI referral system and regulating the access of overseas citizens to health services while in Taiwan. After two decades in existence, problems persist and there is a continuing need to improve Taiwan's NHI. Copyright © 2016 John Wiley & Sons, Ltd.
Pipeflow response in loess‐derived soils to precipitation and groundwater table fluctuations in a temperate humid climate
Authors: Vannoppen W. , Verachtert E. , Poesen J.
Published: October 2016

Piping is a widespread phenomenon in the world and can significantly contribute to the downward movement of water, sediments, and nutrients. This study examines the hydrological functioning of soil pipes in a loess‐derived soil under pasture using hydrometric and hydrochemical analyses. It aims to investigate the relation between pipeflow, rainfall, and groundwater table fluctuations and to determine the dominant source of the water flowing through the soil pipes using both hydrometric and hydrochemical approaches. A rapid pipeflow response is observed when a threshold rainfall depth is exceeded. This threshold depth is larger in the summer (9 mm) compared with that in the winter (4 mm) which is related to the prestorm wetness of the soil. Hydrochemical analyses indicate that both groundwater and rainfall contribute to the pipeflow with a dominance of groundwater. This study shows that pipeflow can be an important hydrological pathway in loess‐derived soils with a clear seasonal pattern in pipeflow responses to rainfall events.