Culture-free, highly sensitive, quantitative detection of bacteria from minimally processed samples using fluorescence imaging by smartphone

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Sajal Shrivastava, Won-Il Lee, Nae-Eung Lee
A critical unmet need in the diagnosis of bacterial infections, which remain a major cause of human morbidity and mortality, is the detection of scarce bacterial pathogens in a variety of samples in a rapid and quantitative manner. Herein, we demonstrate smartphone-based detection of Staphylococcus aureus in a culture-free, rapid, quantitative manner from minimally processed liquid samples using aptamer-functionalized fluorescent magnetic nanoparticles. The tagged S. aureus cells were magnetically captured in a detection cassette, and then fluorescence was imaged using a smartphone camera with a light-emitting diode as the excitation source. Our results showed quantitative detection capability with a minimum detectable concentration as low as 10 cfu/ml by counting individual bacteria cells, efficiently capturing S. aureus cells directly from a peanut milk sample within 10 min. When the selectivity of detection was investigated using samples spiked with other pathogenic bacteria, no significant non-specific detection occurred. Furthermore, strains of S. aureus from various origins showed comparable results, ensuring that the approach can be widely adopted. Therefore, the quantitative fluorescence imaging platform on a smartphone could allow on-site detection of bacteria, providing great potential assistance during major infectious disease outbreaks in remote and resource-limited settings.

Graphical abstract

http://ift.tt/2Ii5hP1

Sorption of selected pharmaceuticals by a river sediment: role and mechanisms of sediment or Aldrich humic substances

Abstract

Sorption of pharmaceuticals onto sediments is frequently related to organic matter content. Thus, the present work aimed to compare the effect of humic substances (HS) extracted from a river sediment versus Aldrich (HS) on the sorption of selected pharmaceuticals onto this river sediment. The results exhibited no "unique" effect of the presence of HS from the same origin. Thus, the sediment HS increased the sorption of sulfamethoxazole (SMX), diclofenac (DCF), and trimethoprim (TMP), but reduced the sorption of atenolol (ATN). The presence of Aldrich HS increased the sorption of TMP and ATN and decreased the sorption of SMX and DCF. Fluorescence quenching measurements revealed that these effects cannot be explained only by the presence of pharmaceutical HS associations. The use of several sorption models suggested that the sorption of SMX, DCF, and ATN involves multilayer mechanisms. Furthermore, it was pointed out that the presence of HS does not change the sorption mechanisms although it was observed interaction between HS and the sediment. Indeed, the sediment HS sorbs onto the sediment whereas the Aldrich HS tends to mobilize organic compounds from the sediment to the solution.

http://ift.tt/2p7pTAr

Modes of selenium occurrence and LCD modeling of selenite desorption/adsorption in soils around the selenium-rich core, Ziyang County, China

Abstract

Studying the modes of selenium occurrence in high-Se soils and its behaviors can improve understanding and evaluating its cycling, flux, and balance in geo-ecosystems and its influence on health. In this paper, using a modified sequential chemical extraction technique, seven operationally defined selenium fractions and Se valence distribution were determined about five soils in which paddy was planted (W1, W2, W3, W4, W5) and five soils in which maize was planted (H1, H2, H3, H4, H5) around the selenium-rich core, Ziyang County, Shaanxi Province, China. The results show that selenium fractions in the soils mainly include sulfide/selenide and base-soluble Se, and ligand-exchangeable Se is also high for five soils in which paddy was planted. For water-soluble Se, Se (IV) is main Se valence and almost no Se (VI) was determined about five soils in which paddy was planted, while almost 1:1 of Se (IV) and Se (VI) coexist about five soils in which maize was planted. For exchangeable Se, similar results were found. For the first time, two typical high-Se soils (W1 soil and H1 soil) were chosen to measure the pH-dependent solid-solution distribution of selenite in the pH range 3–9, and the results were explained using LCD (ligand and charge distribution) adsorption modeling. The desorbed selenite concentrations from the two soils are in general underestimated by the model due to a comparable binding affinity of phosphate and selenite on goethite and much lower amount of total selenite than total reactively adsorbed phosphate. The pH dependency of adsorption of selenite added to the soil can be successfully described with the LCD model for W1 soil. Whereas considering the influence of Al-oxides, by lowering selenite adsorption affinity constant K of Se adsorption on goethite by 16 times, the LCD model can describe the adsorption much better. The results can help to understand selenium cycling, flux, and balance in typical high-Se soils.

http://ift.tt/2Ikd3aL

Distillers’ grains anaerobic digestion residue biochar used for ammonium sorption and its effect on ammonium leaching from an Ultisol

Abstract

The aim of this work was to explore the potential application of biochar from distillers' grains anaerobic digestion residue pyrolyzed at 700 °C (ADR-DG₇₀₀) to ammonium (NH₄⁺) adsorption from aqueous solution, as well as its effect on NH₄⁺ leaching from an Ultisol. The adsorption kinetic of NH₄⁺ on the ADR-DG₇₀₀ could be described by an Elovich model (R² = 0.995), and the combined Langmuir-Freundlich model (R² = 0.997) fitted the isotherm data better than the Langmuir, Freundlich, Redlich-Peterson, and Temkin models with a maximum adsorption of 11.41 mg N g⁻¹. The NH₄⁺ adsorption on ADR-DG₇₀₀ was mainly controlled by the cation exchange, the surface complexation with oxygen-containing functional groups of carboxyl C〓O (C▬O) and carbohydrate C▬OH, as well as the electrostatic interactions with Si▬O▬Si functional group. In addition, the ADR-DG₇₀₀ soil application reduced 2.48–20.67% of NH₄⁺-N leaching loss after nitrogen fertilizer application in an Ultisol. These results suggested that the ADR-DG₇₀₀ could be a sorbent for NH₄⁺-contaminated water as well as an inhibitor for soil NH₄⁺ leaching.

http://ift.tt/2p5DxUS

Heavy metals transfer in the olive tree and assessment of food contamination risk

Abstract

Due to constraints of fresh water for agricultural irrigation, wastewater was used for irrigation of agricultural land as alternative water resources in arid and semi-arid Tunisian regions. However, long-term irrigation may cause contamination by heavy metals in the soil as well as for crops, thus becoming a threat to humans. To understand the effect of irrigation with wastewater on the concentrations of heavy metals Cr, Cu, Mn, Zn, and Pb, in soil and plants, soil samples and plants were collected and analyzed. Results have shown that all soil samples do not exhibit extreme values. The content of heavy metals in the surface layer (0–30 cm) is much higher than that in depth. Overall, the concentrations of Mn, Pb, Cu, Cr, and Zn in soil were found to be lower than the authorized national safety limits. Moreover, the content in both parts of forage crops have not exceeded the WHO standard. For olive trees, no negative values were found in the different organs, which was also true for the extracted oil. An exception happened for the oils produced from fallen olives in direct contact with the wastewater and the soil. Therefore, to ensure food security and wastewater use for irrigation, monitoring and control of pollution is required.

Graphical abstract

Biomass production from treated wastewater without risk

http://ift.tt/2IkTCyH

Quantification of polychlorinated biphenyl contamination using human placenta as biomarker from Punjab Province, Pakistan

Abstract

The present study biomonitored the placental polychlorinated biphenyl (PCB) concentrations in women from Punjab Province, Pakistan, that provides the pioneer data for occurrence and body burden of PCBs in placental tissues from South Asian women. The ∑₃₄PCB concentrations in placental tissues were ranged from 20.2 to 115.98 ng/g lipid weight (lip. wt.), with predominance of tetra-PCB (54.67%). The levels of ∑₈DL-PCBs and ∑₆-indicator PCBs were ranged from 2.03 to 27.64 ng/g (lip. wt.) and 1.71 to 30.8 ng/g (lip. wt.), respectively. The WHO-TEQ2005 values for DL-PCBs were ranged from 1.18 × 10⁻⁵ to 0.067 ng/g (lip. wt.), with highest value evaluated for CB-126. The estimated daily intake (EDI) for DL-PCBs was ranged from 9.27 × 10⁻⁸ to 5.25 × 10⁻⁴ pg WHO-TEQ/kg body weight (bw), which was within the tolerable daily intake (TDI) values established by international organizations. The spatial distribution patterns of Σ₃₄PCB concentrations from study area have shown relative higher concentrations in samples from urban and industrial cities than rural areas, and industrial and urban releases along with e-waste handling were recognized as vital PCB sources in the environment. In order to ascertain the transplacental transfer of PCBs, the fetal growth parameters were correlated with the ∑₃₄PCB concentrations in placental tissues. The relationship between ∑₃₄PCB concentrations in placental tissues and infant's anthropometric measures through multiple linear regression showed a negative correlation of infant's body weight (R² = 0.0728), crown to heel length (R² = 0.068), head circumference (R² = 0.0342), chest circumference (R² = 0.0001), and mid arm circumference (R² = 0.0096) that noticeably highlights the inhibited fetal anthropometric development associated with maternal PCB bioaccumulation. Hence, an immediate elimination of ongoing PCB addition in the studied area has been emphasized and further investigations are suggested to appropriately manage the public and neonatal health risks in the region.

http://ift.tt/2p5DsAy

The toxicity of cadmium ion (Cd 2+ ) to phycocyanin: an in vitro spectroscopic study

Abstract

The pollution of heavy metals is a severer problem for the ecosystems in waters. The toxicity of Cd²⁺ on phycocyanin (PC) is studied in molecular level in this work. The fluorescence quenching of PC is observed by the adding Cd²⁺ from 0 to 500 × 10⁻⁷ mol L⁻¹. From the theoretical calculation and the time-resolved fluorescence decay profiles, the fluorescence quenching of PC by Cd²⁺ is found to be static. The synchronous fluorescence spectra are used to study the change in amino acid residues of PC molecules, indicating that the effect of Cd²⁺ on the Trp of PC is more significant than the Tyr. The UV-Vis absorbance of tetrapyrrole decreases from 0.26 to 0.23 cps with increasing Cd²⁺ concentration, suggesting that Cd²⁺ affects the light adsorption and the photosynthesis function of PC. The circular dichroism spectra reveal that adding Cd²⁺ also changes the secondary structure (α-helix) of PC.

http://ift.tt/2IkVisa

Dermoscopy for the detection and safe extraction of an intracutaneous foreign body Runing Title: Therapeutic Dermoscopy in detection and safe extraction

Publication date: Available online 10 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Sidharth Sonthalia, Abhijeet Kumar Jha, Feroze Kaliyadan




http://ift.tt/2FvBxfr

Fibrosing Vasculitides: A Heuristic for Investigation

Publication date: Available online 10 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Audrey Rutherford, Stephen Erickson, Emily Keimig, Heather Wickless




http://ift.tt/2oXvqdS

Inflammatory arthritis in pediatric patients with morphea

Publication date: Available online 10 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Sakeen W. Kashem, Colleen K. Correll, Richard K. Vehe, Patricia M. Hobday, Bryce A. Binstadt, Sheilagh M. Maguiness
BackgroundMorphea, or 'localized scleroderma', is an inflammatory disorder resulting in fibrosis of the skin and subcutaneous tissues. Joint contractures, arthralgias and functional compromise are recognized associations of pediatric morphea. The co-existence of inflammatory arthritis and morphea is not well-described in the literature.ObjectiveTo investigate the relationship between pediatric morphea and inflammatory arthritis with regards to cutaneous, musculoskeletal and laboratory findings and treatment regimens.MethodsA systematic retrospective chart review of 53 patients with pediatric morphea was performed and analyzed for morphea subtypes, arthritic joint involvement, serum autoantibodies and therapeutic interventions.ResultsEleven out of 53 patients had polyarthritis that involved joints unrelated to the site of the cutaneous morphea. They were mostly female and presented with either the linear or generalized subtypes of morphea. Serum levels of antinuclear antibodies were more significantly elevated in patients with arthritis. All children were treated with methotrexate in addition to other systemic and/or topical immunosuppressive agents.LimitationThis was a small, single center, retrospective study.ConclusionPediatric morphea co-existed with inflammatory arthritis in 11/53 children. Further understanding and appreciation of this relationship may direct more intensive therapy and musculoskeletal screening

Teaser

Pediatric morphea is associated with joint contractures and arthralgia. The findings of this study support the association of inflammatory arthritis with pediatric morphea. Understanding of the relationship between morphea and arthritis in children should lead to increased musculoskeletal vigilance and appropriate systemic therapy.


http://ift.tt/2FvBr7z

Dupilumab for Hand Eczema

Publication date: Available online 10 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Matthew J. Zirwas




http://ift.tt/2oXvzOs

A Deep Learning Approach for Pose Estimation from Volumetric OCT Data

Publication date: Available online 10 March 2018
Source:Medical Image Analysis
Author(s): Nils Gessert, Matthias Schlüter, Alexander Schlaefer
Tracking the pose of instruments is a central problem in image-guided surgery. For microscopic scenarios, optical coherence tomography (OCT) is increasingly used as an imaging modality. OCT is suitable for accurate pose estimation due to its micrometer range resolution and volumetric field of view. However, OCT image processing is challenging due to speckle noise and reflection artifacts in addition to the images' 3D nature. We address pose estimation from OCT volume data with a new deep learning-based tracking framework. For this purpose, we design a new 3D convolutional neural network (CNN) architecture to directly predict the 6D pose of a small marker geometry from OCT volumes. We use a hexapod robot to automatically acquire labeled data points which we use to train 3D CNN architectures for multi-output regression. We use this setup to provide an in-depth analysis on deep learning-based pose estimation from volumes. Specifically, we demonstrate that exploiting volume information for pose estimation yields higher accuracy than relying on 2D representations with depth information. Supporting this observation, we provide quantitative and qualitative results that 3D CNNs effectively exploit the depth structure of marker objects. Regarding the deep learning aspect, we present efficient design principles for 3D CNNs, making use of insights from the 2D deep learning community. In particular, we present Inception3D as a new architecture which performs best for our application. We show that our deep learning approach reaches errors at our ground-truth label's resolution. We achieve a mean average error of 14.89 ± 9.3µm and 0.096 ± 0.072° for position and orientation learning, respectively.

Graphical abstract

http://ift.tt/2FHgLwM

In situ synthesized TiC/Mo-based composites via laser powder bed fusion

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Weiwei Zhou, Xiaohao Sun, Keiko Kikuchi, Naoyuki Nomura, Kyosuke Yoshimi, Akira Kawasaki
A strategy utilizing carbon nanotubes (CNTs) was put forward to synthesize in situ TiC/Mo-based composites via laser powder bed fusion (laser PBF). The functionalized CNTs were dispersed with MoTiAl powders under electrostatic attraction by heteroagglomeration. During laser PBF, individual CNTs reacted with Ti elements and were completely transformed into monocrystalline TiC. Those TiC reinforcements were homogeneously dispersed and intimately contacted the matrix, giving rise to the morphological evolution of a MoTiAl matrix from the nearly columnar to fine equiaxed grains as well as improved mechanical performance. Our finding offers significant guidance for designing and producing advanced Mo-based composites in the application of heat-resistant materials.

Graphical abstract

http://ift.tt/2FH921P

A strategy for improving the mechanical properties of silk fiber by directly injection of ferric ions into silkworm

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Qingsong Liu, Xin Wang, Xiaoyin Tan, Xiaoqian Xie, Yi Li, Ping Zhao, Qingyou Xia
Silk fibers produced by the silkworm, Bombyx mori, are widely used bio-materials due to their superior toughness and elongation. However, the stress and stiffness of silkworm silk are not comparable to the synthetic fiber or other natural silk such as the spider silk. How to improve the mechanical properties of silk fibers has been of great interest. In this paper, we developed a new strategy for improving the mechanical properties of silk fibers by directly injecting ferric ions (Fe³⁺) into silkworm. The Fe³⁺-injected silkworms could produce robust silk fibers with improved stress, stiffness and toughness. Secondary structural analysis indicated that Fe³⁺ promoted the conformation transition of silk from random coil or helical structure to β-sheet structure. These evidences might explain why these fibers became stronger, stiffer and tougher. Trying to unravel the molecular foundation behind this interesting phenomenon, turbidity assays and fluorescence spectroscopy were introduced. The results indicated that Fe³⁺ was able to interact with tyrosine and tryptophan residues within the silk. The crosslinking might act as the "bridge" to form the β-sheet structure, thus increasing the mechanical properties of silk fiber. These findings suggested that Fe³⁺ could be a promising target to modify the mechanical properties of silk fibers.

Graphical abstract

http://ift.tt/2tAKfrq

Collaborative behavior in α lamellae and β phase evolution and its effect on the globularization of TC17 alloy

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Jiao Luo, Peng Ye, Wen Chao Han, Miao Quan Li
The globularization behavior of the basketweave microstructure in TC17 alloy is quantitatively analyzed during deformation and subsequent heat treatment. Collaborative behavior in the α lamellae and β phase evolution are proposed to affect globularization based on the transmission electron microscopy (TEM) and high-resolution electron backscatter diffraction (EBSD) observations as follows: (i) the interleaved α lamellae restrain the rotation of neighboring α lamellae and promote the formation of low-angle boundaries (LABs) and grooves, and then (ii) the β phase has a positive effect on facilitating the complete separation of α lamellae during deformation. During heat treatment, (iii) the formation of the LABs in the β grain interiors accelerates the appearance of necklace-like α grains, and (iv) the α lamellae promotes the break-up of β phase while the β phase has a positive effect on facilitating the complete separation of α lamellae. In other words, Collaborative behavior in α lamellae and β phase evolution promotes the globularization of TC17 alloy containing a basketweave microstructure. Except for the boundary splitting and termination migration, the mechanism of substructure rotation also participates in the globularization of TC17 alloy containing a basketweave microstructure, which is different to that of the alloys containing a colony microstructure.

Graphical abstract

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Optimisation of interface formation by shear inclination: Example of aluminium-cooper hybrid produced by ECAP with back-pressure

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Alexander E. Medvedev, Rimma Lapovok, Eric Koch, Heinz Werner Höppel, Mathias Göken
Hybrid materials present a convenient way of combining properties of more than one material in one product. However, there are problems associated with such manufacturing, particularly, in relation to the properties of the interface between components. Intermetallic compounds can potentially form in this area, whose size and composition can have a profound effect on mechanical properties of the product. In this work, we investigate the effect of temperature, mutual arrangement and hydrostatic pressure on the quality of the interface between Al and Cu parts, processed simultaneously by severe plastic deformation. We show that three intermetallic compounds - θ-Al2Cu, ζ2-Al3Cu4-δ and γ1-Al4Cu9 - form on the interface. It is shown that the formation of these phases on the interface between aluminium and copper highly depends on the combination of diffusion and recrystallization process.

Graphical abstract

http://ift.tt/2tuGiVi

Scalable manufacturing of immiscible AlBi alloy by self-assembled nanoparticles

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Chezheng Cao, Weiqing Liu, Zhiwei Liu, Jiaquan Xu, Injoo Hwang, Igor De Rosa, Xiaochun Li
Immiscible AlBi alloy, with a miscibility gap in the liquid state is not only scientifically important, but also it can offer outstanding self-lubricating properties. However, it is still difficult to control the distribution and size of minority Bi phase during cooling and solidification. Here we show that by applying a scalable molten salt assisted incorporation process, TiC nanoparticles can be incorporated in Al matrix to produce Al-TiC master nanocomposites, which can be readily used to process AlBi immiscible alloy and restrict the size of minority Bi phase. TiC nanoparticles can be self-assembled on the AlBi interface and restrict Bi phase size substantially. In addition, submicron minority Bi phase can be achieved by combining the addition of nanoparticles with high cooling rates. Mechanical properties of AlBi immiscible alloys can be further enhanced by the addition of Cu element and cold rolling.

Graphical abstract

http://ift.tt/2FFISMN

Formation and application of hierarchical calcium silicate-calcium sulfate whiskers

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Yu-rong Yang, Qing-jie Zhang, Wei Cai, Mei-gui Yi, Lan Xiang
A facile method was designed for synthesizing hierarchical calcium silicate-calcium sulfate whiskers (H-CSW) via treatment of the calcium sulfate whiskers (CSW) in sodium silicate solution. Calcium silicate nanoparticles with a size of 70–100nm were uniformly anchored on H-CSW surfaces and the specific surface areas of the whiskers increased from 6.0m²·g⁻¹ to 29.1m²·g⁻¹. The addition of 2.0wt% of H-CSW in epoxy composite led to the increase of 10% in flexural strength, 16% in flexural modulus, 18% in storage modulus (30°C) and 8°C in glass transition temperature owing to the enhanced mechanical interlocking among H-CSW and the epoxy matrix.

Graphical abstract

http://ift.tt/2tuGhRe

Regarding “Epidemiology and risk factors for Clostridium difficile-associated diarrhea in adult inpatients in a university hospital in China: Methodologic issues”

Publication date: Available online 9 March 2018
Source:American Journal of Infection Control
Author(s): Chenjie Tang, Yi Cui, Genyan Liu




http://ift.tt/2p5sJWO

Comparison of Self-Report Versus Sensor-Based Methods for Measuring the Amount of Upper Limb Activity Outside the Clinic

Publication date: Available online 10 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kimberly J. Waddell, Catherine E. Lang
ObjectiveTo compare self-reported with sensor-measured upper limb (UL) performance in daily life for individuals with chronic (≥6mo) UL paresis poststroke.DesignSecondary analysis of participants enrolled in a phase II randomized, parallel, dose-response UL movement trial. This analysis compared the accuracy and consistency between self-reported UL performance and sensor-measured UL performance at baseline and immediately post an 8-week intensive UL task-specific intervention.SettingOutpatient rehabilitation.ParticipantsCommunity-dwelling individuals with chronic (≥6mo) UL paresis poststroke (N=64).InterventionsNot applicable.Main Outcome MeasuresMotor Activity Log amount of use scale and the sensor-derived use ratio from wrist-worn accelerometers.ResultsThere was a high degree of variability between self-reported UL performance and the sensor-derived use ratio. Using sensor-based values as a reference, 3 distinct categories were identified: accurate reporters (reporting difference ±0.1), overreporters (difference >0.1), and underreporters (difference <−0.1). Five of 64 participants accurately self-reported UL performance at baseline and postintervention. Over half of participants (52%) switched categories from pre-to postintervention (eg, moved from underreporting preintervention to overreporting postintervention). For the consistent reporters, no participant characteristics were found to influence whether someone over- or underreported performance compared with sensor-based assessment.ConclusionsParticipants did not consistently or accurately self-report UL performance when compared with the sensor-derived use ratio. Although self-report and sensor-based assessments are moderately associated and appear similar conceptually, these results suggest self-reported UL performance is often not consistent with sensor-measured performance and the measures cannot be used interchangeably.



http://ift.tt/2GcezLv

Colloidal aggregation: From screening nuisance to formulation nuance

Publication date: Available online 10 March 2018
Source:Nano Today
Author(s): Ahil N. Ganesh, Eric N. Donders, Brian K. Shoichet, Molly S. Shoichet
It is well known that small molecule colloidal aggregation is a leading cause of false positives in early drug discovery. Colloid-formers are diverse and well represented among corporate and academic screening decks, and even among approved drugs. Less appreciated is how colloid formation by drug-like compounds fits into the wider understanding of colloid physical chemistry. Here we introduce the impact that colloidal aggregation has had on early drug discovery, and then turn to the physical and thermodynamic driving forces for small molecule colloidal aggregation, including the particulate nature of the colloids, their critical aggregation concentration-governed formation, their mechanism of protein adsorption and subsequent inhibition, and their sensitivity to detergent. We describe methods that have been used extensively to both identify aggregate-formers and to study and control their physical chemistry. While colloidal aggregation is widely recognized as a problem in early drug discovery, we highlight the opportunities for exploiting this phenomenon in biological milieus and for drug formulation.

Graphical abstract

http://ift.tt/2FHFnpe

Why France is making eight new vaccines mandatory

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Jeremy K. Ward, James Colgrove, Pierre Verger
France is one of the countries with the highest prevalence of vaccine hesitancy in the world. In an attempt to raise vaccination coverages, the French government made on January 1, 2018 eight more vaccines mandatory in addition to the three required until then. The process that led to this policy choice is of particular interest. We describe how vaccines became contentious in France and how French authorities came to view mandatory vaccination as the solution to the rise in vaccine hesitancy. In a bold move, French public health authorities turned to a new type of institutional device grounded in the ideal of democracy and public participation to political decision-making: "a citizen consultation". This consultation anchored the idea that legal coercion could be the solution to France's crisis with vaccines. Time will tell whether the French extension of mandatory vaccination will reduce tensions around vaccines.



http://ift.tt/2p5JSzp

Factors contributing to declination of annual influenza vaccination by healthcare workers caring for cancer patients: An Australian experience

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): T.C. Surtees, B.W. Teh, M.A. Slavin, L.J. Worth
Healthcare workers (HCWs) at an Australian cancer centre were evaluated using a voluntary declination form program to determine factors contributing to declination of annual influenza vaccination. Overall, 1835/2041 HCWs (89.9%) completed a consent or declination form; 1783 were vaccinated and 52 declined. Staff roles with minimal patient contact were significantly associated with lower vaccine uptake (adjusted odds ratio 0.48, 95% confidence interval 0.23–0.99). Reasons for vaccine refusal included personal choice (41%), previous side-effect/s (23.1%), and medical reasons (23.1%). Of these, a large proportion may not be amenable to intervention, and this must be considered in setting threshold targets for future campaigns.



http://ift.tt/2Ikelm6

It could have been much worse: The Minnesota measles outbreak of 2017

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Timothy F. Leslie, Paul L. Delamater, Y. Tony Yang
In 2017, Minnesota battled its largest measles outbreak in nearly 30 years, with 79 cases, most of them Somali-American children. In this study, we gathered vaccination and enrollment data for incoming kindergarteners in Minnesota over fall 2012–2016 from the Minnesota Department of Health. We also gathered the number of measles cases by county in 2017. We found that MMR coverage has substantial variation across districts and district types. The minimum MMR coverage is 58.3% and the maximum is 100%. Private schools, which represent approximately six percent of Minnesota's kindergarten enrollment, have a substantially lower coverage rate, with an overall coverage of 83.00%. The 2017 outbreak was relatively isolated. However, the MMR coverage data suggests that other communities could have been at risk given their geographic proximity to the outbreak and modest coverage rates.



http://ift.tt/2p3SNSf

Evaluation of the immunogenic capability of the BCG strains BCGΔBCG1419c and BCGΔBCG1416c in a three-dimensional human lung tissue model

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Venkata Ramanarao Parasa, Jeronimo Rose, Luis Alberto Castillo-Diaz, Michel de Jesús Aceves-Sánchez, Perla Jazmín Vega-Domínguez, Maria Lerm, Mario Alberto Flores-Valdez
Tuberculosis (TB) still remains as an unmet global threat. The current vaccine is not fully effective and novel alternatives are needed. Here, two vaccine candidate strains derived from BCG carrying deletions in the BCG1416c or BCG1419c genes were analysed for their capacity to modulate the cytokine/chemokine profile and granuloma formation in a human lung tissue model (LTM). We show that the clustering of monocytes, reminiscent of early granuloma formation, in LTMs infected with BCG strains was similar for all of them. However, BCGΔBCG1419c, like M. tuberculosis, was capable of inducing the production of IL-6 in contrast to the other BCG strains. This work suggests that LTM could be a useful ex vivo assay to evaluate the potential immunogenicity of novel TB vaccine candidates.



http://ift.tt/2IeTxN0

Vaccine-preventable disease incidence of pneumococcal conjugate vaccine in the Finnish invasive pneumococcal disease vaccine trial

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Arto A. Palmu, Jukka Jokinen, Heta Nieminen, Hanna Rinta-Kokko, Esa Ruokokoski, Taneli Puumalainen, Marta Moreira, Lode Schuerman, Dorota Borys, Terhi M. Kilpi
Estimation of the full disease burden caused by Streptococcus pneumoniae is challenging due to the difficulties in assigning the aetiology especially in lower and upper respiratory infections. We estimated the pneumococcal disease burden by using the vaccine-preventable disease incidence (VPDI) of PHiD-CV10 vaccine (GSK) in our clinical trial setting.Finnish Invasive Pneumococcal disease (FinIP) trial was a cluster-randomized, double-blind trial in children <19 months who received PHiD-CV10 in 52 clusters or hepatitis B/A vaccine as control in 26 clusters according to 3+1 or 2+1 schedules (infants < 7 months) or catch-up schedules (children 7–18 months). Outcome data were collected using Finnish routine health-care registers, consisting of THL National Infectious Diseases Register, THL Care register, and Benefits Register of Social Insurance Institution of Finland. Blinded follow-up lasted from the date of first vaccination (trial enrolment Feb-2009 through Aug-2010) to January 31, 2012 for Invasive Pneumococcal Disease (IPD) and to end of December 2011 for four other outcomes: non-laboratory-confirmed IPD, hospital-diagnosed pneumonia, tympanostomy tube placements, and antimicrobial purchases. VPDI was estimated as difference in disease incidences between PHiD-CV10 clusters and control clusters.Altogether >47,000 children were enrolled. In 30,527 vaccinated infants <7 months at first dose, the VPDIs per 100,000 person-years were 75 for laboratory-confirmed IPD, 210 for non-laboratory-confirmed IPD, 271 for hospital-diagnosed pneumonia, 1143 for any tympanostomy tube placements and 11,381 for antimicrobial outpatient prescription, mainly due to otitis media.In a European developed-country setting, over 95% of the disease episode reductions in vaccinated children were seen in mild upper respiratory infections. The VPDIs of severe diseases are underestimated, because the majority of invasive disease goes undetected with routine blood-culture-based definitions. Evaluation of the absolute reduction achievable with vaccinations using sensitive case detection is essential for understanding the full disease burden, for valid cost-effectiveness analyses and for appropriate vaccination policy decisions.Registration: ClinicalTrials.gov, NCT00861380 and NCT00839254.



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Editorial Board/Aims and Scope

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14





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Immunization education for internal medicine residents: A cluster-randomized controlled trial

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Jennifer A. Whitaker, Caroline M. Poland, Thomas J. Beckman, John B. Bundrick, Rajeev Chaudhry, Diane E. Grill, Andrew J. Halvorsen, Jill M. Huber, Mary J. Kasten, Karen F. Mauck, Ramila A. Mehta, Timothy Olson, Kris G. Thomas, Matthew R. Thomas, Abinash Virk, Majken T. Wingo, Gregory A. Poland
PurposeThe aims of this study are to evaluate the impact of a novel immunization curriculum based on the Preferred Cognitive Styles and Decision Making Model (PCSDM) on internal medicine (IM) resident continuity clinic patient panel immunization rates, as well as resident immunization knowledge, attitudes, and practices (KAP).MethodsA cluster-randomized controlled trial was performed among 143 IM residents at Mayo Clinic to evaluate the PCSDM curriculum plus fact-based immunization curriculum (intervention) compared to fact-based immunization curriculum alone (control) on the outcomes of resident continuity clinic patient panel immunization rates for influenza, pneumococcal, tetanus, pertussis, and zoster vaccines. Pre-study and post-study immunization KAP surveys were administered to IM residents.ResultsNinety-nine residents participated in the study. Eighty-two residents completed pre-study and post-study surveys. Influenza and pertussis immunization rates improved for both intervention and control groups. There was no significant difference in immunization rate improvement between the groups. Influenza immunization rates improved significantly by 33.4% and 32.3% in the intervention and control groups, respectively. The odds of receiving influenza immunization at the end of the study relative to pre-study for the entire study cohort was 4.6 (p < 0.0001). The odds of having received pertussis immunization at the end of the study relative to pre-study for the entire study cohort was 1.2 (p = 0.0002). Both groups had significant improvements in immunization knowledge. The intervention group had significant improvements in multiple domains that assessed confidence in counseling patients on immunizations.ConclusionsFact-based immunization education was useful in improving IM resident immunization rates for influenza and pertussis. The PCSDM immunization curriculum did not lead to increases in immunization rates compared with the fact-based curriculum, but it did significantly increase resident confidence in communicating with patients about vaccines.



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Generation, safety and immunogenicity of an Actinobacillus pleuropneumoniae quintuple deletion mutant SLW07 (ΔapxICΔapxIICΔorf1ΔcpxARΔarcA)

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Fangyan Yuan, Jinlin Liu, Wujin You, Weicheng Bei, Chunlai Wang, Jin Zhao, Yiongxiang Tian, Siguo Liu
We inactivated a virulence determinant, ArcA, in an Actinobacillus pleuropneumoniae quadruple deletion mutant SLW06 (ΔapxICΔapxIICΔorf1ΔcpxAR, serovar 1), and a quintuple deletion mutant SLW07 was generated. SLW07 showed decreased adherence to and invasion of host cells, compared to its parent strain SLW06. SLW07 was more sensitive in RAW264.7 macrophage-mediated phagocytosis and clearance. SLW07 was less virulent in mice. An immunization assay indicated that both SLW07 and SLW06 preferentially stimulated T helper cell type 2 response in mice. Live vaccines induced the production of interleukin-6 and tumor necrosis factor-α by splenic lymphocytes. Furthermore, the protective immunity of SLW07 was not affected after ArcA mutation. Immunization with SLW07 could provide a complete protection following virulent A. pleuropneumoniae challenge in mice. Our results suggest that SLW07 is a promising live vaccine candidate, which is further attenuated from and shares similar protective efficacy with its quadruple deletion parent SLW06.



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Safety implication of Salmonella based Brucella vaccine candidate in mice and in vitro human cell culture

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Jonathan Lalsiamthara, Amal Senevirathne, Mi Young So, John Hwa Lee
An anti-Brucella vaccine candidate comprising rough Salmonella vector delivering Brucella antigens was developed. This system provides a platform for live Brucella-free vaccine development as it can mimic active-intracellular infection of Brucella organism. Exploiting this phenomenon thus provides significant protection at a single dose and also re-assured the safety. To date, no human anti-Brucella vaccines are available, owing to the lack of safe and effective formulation. This study investigated the safety of the vaccine formulation in mice model and in vitro human cell cultures. The experiment was designed to determine the LD50 of the vaccine formulation. The vaccine formulation did not induce any mortality even when mice were administered at 8 × 10⁹ CFU per oral or per subcutaneous (SC), which was 100-times more than the actual vaccine dose intended for mice model. In contrast, wild-type (WT) Salmonella positive control strain induced 100% mortality at 8 × 10⁷ CFU per mice via oral or SC routes. Interaction of the vaccine with phagocytic (THP-1 derived macrophage) and non-phagocytic (Caco-2) human cell lines as well as human PBMC was investigated. In in vitro experiments, inflammatory and pyretic cytokines TNF-α, and IL-1β inductions were significantly lower in vaccine group as compared to WT group. Further, apoptosis, nitric oxide synthase and cytotoxicity inductions were comparable and not exacerbated, given that the strain is based on a rough bacterial vector that may have endotoxic lipid-A more readily exposed. These findings corroborated that the vaccine formulation is highly safe in mice model and is relatively mild in the induction of inflammatory cytokines and cellular changes in human cell lines.



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A plant-produced vaccine protects mice against lethal West Nile virus infection without enhancing Zika or dengue virus infectivity

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Huafang Lai, Amber M. Paul, Haiyan Sun, Junyun He, Ming Yang, Fengwei Bai, Qiang Chen
West Nile virus (WNV) has caused multiple global outbreaks with increased frequency of neuroinvasive disease in recent years. Despite many years of research, there are no licensed therapeutics or vaccines available for human use. One of the major impediments of vaccine development against WNV is the potential enhancement of infection by related flaviviruses in vaccinated subjects through the mechanism of antibody-dependent enhancement of infection (ADE). For instance, the recent finding of enhancement of Zika virus (ZIKV) infection by pre-exposure to WNV further complicates the development of WNV vaccines. Epidemics of WNV and the potential risk of ADE by current vaccine candidates demand the development of effective and safe vaccines. We have previously reported that the domain III (DIII) of the WNV envelope protein can be readily expressed in Nicotiana benthamiana leaves, purified to homogeneity, and promote antigen-specific antibody response in mice. Herein, we further investigated the in vivo potency of a plant-made DIII (plant-DIII) in providing protective immunity against WNV infection. Furthermore, we examined if vaccination with plant-DIII would enhance the risk of a subsequent infection by ZIKV and Dengue virus (DENV). Plant-DIII vaccination evoked antigen-specific cellular immune responses as well as humoral responses. DIII-specific antibodies were neutralizing and the neutralization titers met the threshold correlated with protective immunity by vaccines against multiple flaviviruses. Furthermore, passive administration of anti-plant DIII mouse serum provided full protection against a lethal challenge of WNV infection in mice. Notably, plant DIII-induced antibodies did not enhance ZIKV and DENV infection in Fc gamma receptor-expressing cells, addressing the concern of WNV vaccines in inducing cross-reactive antibodies and sensitizing subjects to subsequent infection by heterologous flavivirus. This study provides the first report of a WNV subunit vaccine that induces protective immunity, while circumventing induction of antibodies with enhancing activity for ZIKV and DENV infection.



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Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Mun Peak Nyon, Lanying Du, Chien-Te Kent Tseng, Christopher A. Seid, Jeroen Pollet, Kevin S. Naceanceno, Anurodh Agrawal, Abdullah Algaissi, Bi-Hung Peng, Wanbo Tai, Shibo Jiang, Maria Elena Bottazzi, Ulrich Strych, Peter J. Hotez
Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377–588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.



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Lack of nervous necrosis virus (NNV) neutralizing antibodies in convalescent sevenband grouper Hyporthodus septemfasciatus after NNV infection

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Hyun Jung Gye, Myung-Joo Oh, Toyohiko Nishizawa
Viral nervous necrosis (VNN) is caused by nervous necrosis viruses (NNVs) belonging to genus Betanodavirus (Nodaviridae). It is one of the most serious diseases in aquaculture industry worldwide. In the present study, the kinetics of NNV-infectivity and NNV-specific antibodies in convalescent sevenband grouper Hyporthodus septemfasciatus after NNV infection was determined. When fish were infected with NNV at 17.5 °C, and reared for 84 days at natural seawater temperature (increasing rate: approximately 0.1 °C/day), NNV infectivity peaked on day 14 with 10^7.80 TCID50/g at the highest, and declined to below the detection limit. When convalescent fish were reared at 27 °C, and re-infected with NNV at 10^4.3 or 10^6.3 TCID50/fish, no mortality was observed although NNV multiplied up to 10^8.80 and 10^7.80 TCID50/g at the highest, respectively, suggesting NNV-specific immune response. It also revealed that convalescent fish were re-infected by NNV although NNV multiplication was strongly regulated. Interestingly, NNV-specific antibodies were detectable in 20% and ≥80% of convalescent fish before and after re-infection with NNV, respectively. However, no NNV-neutralizing activity was detected before and after re-infection in almost all of the convalescent fish. Therefore, NNV-neutralizing antibodies might not be necessary for the protection of convalescent fish against NNV re-infection after previous NNV infection.



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H5N2 vaccine viruses on Russian and US live attenuated influenza virus backbones demonstrate similar infectivity, immunogenicity and protection in ferrets

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Rita Czakó, Leatrice Vogel, Troy Sutton, Yumiko Matsuoka, Florian Krammer, Zhongying Chen, Hong Jin, Kanta Subbarao
The continued detection of zoonotic influenza infections, most notably due to the avian influenza A H5N1 and H7N9 subtypes, underscores the need for pandemic preparedness. Decades of experience with live attenuated influenza vaccines (LAIVs) for the control of seasonal influenza support the safety and effectiveness of this vaccine platform. All LAIV candidates are derived from one of two licensed master donor viruses (MDVs), cold-adapted (ca) A/Ann Arbor/6/60 or ca A/Leningrad/134/17/57. A number of LAIV candidates targeting avian H5 influenza viruses derived with each MDV have been evaluated in humans, but have differed in their infectivity and immunogenicity. To understand these differences, we generated four H5N2 candidate pandemic LAIVs (pLAIVs) derived from either MDV and compared their biological characteristics in vitro and in vivo. We demonstrate that all candidate pLAIVs, regardless of gene constellation and derivation, were comparable with respect to infectivity, immunogenicity, and protection from challenge in the ferret model of influenza. These observations suggest that differences in clinical performance of H5 pLAIVs may be due to factors other than inherent biological properties of the two MDVs.



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Attenuation, safety, and efficacy of a QX-like infectious bronchitis virus serotype vaccine

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Shihong Yan, Jing Zhao, Deqiong Xie, Xiuying Huang, Jinlong Cheng, Ye Guo, Changqing Liu, Zhijun Ma, Huiming Yang, Guozhong Zhang
Avian infectious bronchitis (IB) is a highly contagious disease caused by avian infectious bronchitis virus (IBV), which is a considerable economic threat to the poultry industry. QX-like IBV strains have increasingly emerged in China in recent years. Hence, development of a specific vaccine to guard against their potential threat is important. In this study, we sought to develop an attenuated vaccine strain. First, attenuated QX-like IBV strain SZ130 was created by continuous passage in chicken embryos for 130 generations, and then its safety was tested. We also evaluated the protective efficacy of different doses of SZ130 against challenge with QX-like IBV field strain SD in chickens. SZ130-infected birds did not experience IB-like signs and organ lesions. Additionally, an excellent protective effect of SZ130 vaccination was observed when vaccinated birds were challenged with SD, with no clinical signs or gross lesions, decreased target tissue replication rates, and lower ciliostasis scores in all immunized groups. These findings indicate that attenuated IBV strain SZ130 is highly safe in chicks and may serve as an effective vaccine against the threat posed by QX-like IBV strains.



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Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: The NSW Public Health Network case-control study

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Nathan Saul, Kevin Wang, Shopna Bag, Heather Baldwin, Kate Alexander, Meena Chandra, Jane Thomas, Helen Quinn, Vicky Sheppeard, Stephen Conaty
BackgroundInfants are at the highest risk of severe complications – including death – as a result of pertussis infection. Controlling pertussis in this group has been challenging, particularly in those too young to be vaccinated. Following revised national recommendations in March 2015, the state of New South Wales, Australia, introduced a funded maternal vaccination campaign at 28 – 32 weeks of gestation using a 3-component tetanus-diphtheria-acellular pertussis vaccine (dTpa; Boostrix, GSK). This study aimed to assess the effectiveness of maternal vaccination and add to the growing body of evidence for this strategy.MethodsA 1:1 matched case-control study was conducted between 16 August 2015 and 17 August 2016. Cases were laboratory or doctor notified, laboratory confirmed (nucleic acid testing or culture) and aged <6 months at onset. Each control infant was randomly selected from public hospital births in the same geographical area in the period up to 3 days before and after the case's birthdate. Odds ratios (OR) were calculated using conditional logistic regression. Vaccine effectiveness (VE) was calculated as 1 – OR.FindingsIn total, 117 cases and 117 controls were recruited. The overall VE estimate was non-significantly protective for infants <6 months old (VE 39%, 95% CI −12 to 66%). Higher VE was observed for infants <3 months old (VE 69%, 95% CI 13–89%) and against hospitalisation (VE 94%, 95% CI 59–99%).InterpretationMaternal pertussis vaccination with a 3-component acellular vaccine was found to be highly effective at preventing severe disease in infants, but was less effective at preventing disease which did not require hospitalisation. The overall VE reported in this study was lower than in prior studies and suggests that maternal vaccination, while an effective strategy at preventing severe pertussis, is less effective at protecting against infection or mild disease.



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Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Elodie Meynet, David Laurin, Jean Luc Lenormand, Boubou Camara, Bertrand Toussaint, Audrey Le Gouëllec
Pseudomonas aeruginosa (Pa) is a significant cause of morbidity and mortality, especially in cystic fibrosis patients. Its eradication is difficult due to a wide phenotypic adaptability and an increase of its resistance to antibiotics. After the failure of several recombinant vaccines which mainly triggered humoral response, live-attenuated vaccines received attention thanks to their ability to elicit a broad immunity with both humoral- and cell-mediated responses, essential to fight this pathogen. In this study, we developed an innovative and safer live-attenuated Pa vaccine based on a Killed But Metabolically Active (KBMA) attenuation method. KBMA Pa has been further rationally designed to overexpress beneficial effectors like the type 3 secretion system apparatus. We demonstrated that KBMA Pa elicits a high and broad humoral response in mice against several antigens of particular interest such as OprF and PcrV proteins. Moreover, we assessed cytokines in the serum of immunized mice and showed that KBMA Pa elicits Th1, Th2 and especially Th17 pathways of cell-mediated immune responses. Th17 pathway involvement was also confirmed after specific stimulation of helper T cells in immunized mice. Finally, we showed that this vaccine is safe and has a protective effect in a murine acute pulmonary infectious challenge. In conclusion, KBMA Pa is a new platform with high potential for the development of a vaccine against Pa.

Graphical abstract

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Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging A/ASIA/G-VII lineage

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Ryan Waters, Anna B. Ludi, Veronica L. Fowler, Ginette Wilsden, Clare Browning, Simon Gubbins, Bob Statham, Abdelghani Bin-Tarif, Valerie Mioulet, David J. King, Claire Colenutt, Emma Brown, Pascal Hudelet, Donald P. King
In 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East were discovered to be caused by a viral lineage (A/ASIA/G-VII), which has recently emerged from the Indian sub-continent. In vitro vaccine matching data generated by the World Reference Laboratory (WRLFMD) indicated that A/ASIA/G-VII field viruses were poorly matched with vaccines (A-SAU-95, A22 IRQ and A-IRN-05) that are already used in the region. In order to assess the likely performance of one of these commercially available FMD vaccines, sixteen cattle were vaccinated with a polyvalent vaccine which contained two serotype A components (A-SAU-95 and A-IRN-05) with a homologous potency of at least 6PD50, and two cattle were left unvaccinated as controls. Twenty-one days later, all 18 cattle were challenged by tongue inoculation with an FMDV field isolate A/IRN/22/2015 from the A/ASIA/G-VII lineage, in line with the European Pharmacopeia PPG test conditions. The two control animals developed generalised FMD, and 7/16 vaccinated animals developed at least one foot lesion, thus only 56.3% were defined as protected. For the vaccine components, there was a significant increase in the probability of protection with increasing serological titres for A-SAU-95 (p = 0.03), but not for A-IRN-05 (p = 0.42). Analysis of FMDV in blood and nasal swabs suggested that vaccination reduced shedding and potential onward spread of FMD virus even if the animal developed foot lesions. In summary, the results from this study suggest that whilst this vaccine would not be appropriate for use in an emergency situation (in previously FMD-free countries), it may be partially effective in the field in endemic countries where repeat prophylactic vaccination is practiced. For emergency reactive vaccination, the findings from this study support the idea that a new vaccine strain should be developed that is tailored to the A/ASIA/G-VII lineage.



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Immunogenicity and safety of one or two doses of the quadrivalent meningococcal vaccine MenACWY-TT given alone or with the 13-valent pneumococcal conjugate vaccine in toddlers: A phase III, open-label, randomised study

Publication date: 27 March 2018
Source:Vaccine, Volume 36, Issue 14
Author(s): Clare L. Cutland, Terry Nolan, Scott A. Halperin, Zafer Kurugol, Khatija Ahmed, Kirsten P. Perrett, Peter Richmond, Helen S Marshall, Mehmet Ceyhan, Devayani Kolhe, Marjan Hezareh, Marie Van Der Wielen
BackgroundWe evaluated the immunogenicity and safety of 1 and 2 doses of quadrivalent meningococcal serogroup A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT) given alone or co-administered with 13-valent pneumococcal conjugate vaccine (PCV13) in toddlers.MethodsIn this phase III, open-label, controlled, multicentre study (NCT01939158), healthy toddlers aged 12–14 months were randomised into 4 groups to receive 1 dose of MenACWY-TT at month (M) 0 (ACWY_1), 2 doses of MenACWY-TT at M0 and M2 (ACWY_2), MenACWY-TT and PCV13 at M0 (Co-ad), or PCV13 at M0 and MenACWY-TT at M2 (PCV13/ACWY). Immune responses were assessed 1 month post-each vaccination. Solicited and unsolicited symptoms were recorded for 4 and 31 days post-each vaccination, respectively; serious adverse events (SAEs) and new onset of chronic illnesses (NOCIs) up to M9 from first vaccination.Results802 toddlers were vaccinated. Post-dose 1 of MenACWY-TT, ≥92.8% of toddlers had rSBA titres ≥1:8, and ≥62.5% had hSBA titres ≥1:4 for each meningococcal serogroup. Post-dose 2 of MenACWY-TT, rSBA titres ≥1:8 were observed in ≥98.0% and hSBA titres ≥1:4 in ≥95.3% of toddlers. Percentages of toddlers with hSBA titres ≥1:4 were higher after 2 doses versus 1 dose of MenACWY-TT for MenW (97.1% versus 62.5–68.9%) and MenY (95.3% versus 64.3–67.6%). Non-inferiority of immune responses to co-administered MenACWY-TT and PCV13 over their separate administration was demonstrated. AEs incidence was comparable among groups. SAEs were reported for 4.9%, 5.1%, 5.5% and 7.5%, and NOCIs for 2.0%, 3.0%, 0.5% and 3.5% of toddlers in the ACWY_1, ACWY_2, Co-ad and PCV13/ACWY groups, respectively; 4 SAEs reported in 3 toddlers were vaccine-related. Two fatal vaccine-unrelated SAEs were reported.ConclusionMenACWY-TT was immunogenic when administered as a single dose at 12–14 months of age. A second dose in toddlers increased hSBA responses against MenW and MenY. MenACWY-TT and PCV13 can be co-administered without impairing the immunogenicity or safety profile of either vaccine.



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Dose dependence of accelerated repopulation in head and neck cancer: Supporting evidence and clinical implications

Publication date: Available online 10 March 2018
Source:Radiotherapy and Oncology
Author(s): Igor Shuryak, Eric J. Hall, David J. Brenner
Background and purposeAccelerated repopulation (AR) can compromise tumor control after conventional radiotherapy for fast-growing tumors. Standard AR models assume it begins at a fixed time, with repopulation rates independent of the number of clonogens killed. We investigate the validity and significance of an alternative model where onset-time and rate of AR depend on the number of clonogens killed, and thus on dose and dose-fractionation.Materials and methodsWe analyzed tumor control (TCP) from randomized trials for head and neck cancer (HNC, 7283 patients), featuring wide ranges of doses, times, and fractionation-schemes. We used the linear-quadratic model with the standard dose-independent AR model, or with an alternative dose-dependent model, where AR onset and rate depend on clonogen killing.ResultsThe alternative dose-dependent model of AR provides significantly-improved descriptions of a wide range of randomized clinical data, relative to the standard dose-independent model. This preferred model predicts that, for currently-used HNC fractionation schemes, the last 5 fractions do not increase TCP, but simply compensate for increased accelerated repopulation.ConclusionsThe preferred dose-dependent AR model predicts that, for standard fractionation schemes currently used to treat HNC, the final week (5 fractions) could be eliminated without compromising TCP, but resulting in significantly decreased late sequelae due to the lower overall dose.



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Use of extracranial radiation therapy in metastatic melanoma patients receiving immunotherapy

Publication date: Available online 11 March 2018
Source:Radiotherapy and Oncology
Author(s): Prashant Gabani, Clifford G. Robinson, George Ansstas, Tanner M. Johanns, Jiayi Huang
PurposeExplore the patterns of use of extracranial radiation therapy (RT) in metastatic melanoma patients receiving immunotherapy, its potential association with OS, the impact of the site and timing of RT on clinical outcomes when combined with immunotherapy.Materials and methodsPatients with extracranial metastatic melanoma who received immunotherapy with or without extracranial RT from 2004 to 2013 were obtained from the National Cancer Database. Multivariable Cox regression analysis was used to evaluate factors associated with overall survival (OS). Subset analyses comparing outcomes in patients receiving RT to bone metastases versus soft tissue metastases were also performed. OS was compared using the Kaplan–Meier and log-rank statistics.ResultsA total of 1675 patients were identified: 1387 received immunotherapy alone and 288 received immunotherapy plus RT. An increase in the utilization of RT as well as SBRT was noted over time. The rate of RT use was 11.5% (0% with SBRT) in 2004 and gradually rose to 19.8% (27.0% with SBRT) in 2013 (P = 0.04). The median OS was 15.4 vs. 19.4 months in the immunotherapy plus RT and immunotherapy alone groups, respectively (P = 0.02). However, on multivariable analysis, RT was not associated with worse OS. The poor OS in the RT group was confined to the patients who received RT to bone metastases, but not in patients who received RT to soft tissue metastases. In subset analyses of patients irradiated to soft tissue, RT administered at least 30 days before immunotherapy was associated with a higher OS than RT administered within 30 days or 30 days after immunotherapy: median 26.1 months vs. 16.0 months (P = 0.009) vs. 15.4 months (P = 0.004), respectively.ConclusionsThis study demonstrates that extracranial RT plays an increasing role in the management of metastatic melanoma patients in the era of immunotherapy. The site and the timing of RT may have important interaction with immunotherapy, and need to be carefully considered in future clinical trials.



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Photodynamic therapy of Curcuma longa extract stimulated with blue light against Aggregatibacter actinomycetemcomitans

Publication date: Available online 10 March 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Darika Saitawee, Aroon Teerakapong, Noppawan Phumala Morales, Paiboon Jitprasertwong, Doosadee Hormdee
Background and objectiveCurcumin, one of an established curcuminoid substances extracted from Curcuma longa, has been used as a photosensitizer (PS) in photodynamic therapy (PDT). Curcuminoid substances has been reported to have benefits in treating dental chronic infection and inflammation diseases, such as chronic periodontitis. The purpose of this study was to find the optimum concentration of Curcuma longa (CL) extract, containing all curcuminoid substances, and the power density of blue light (BL) in photodynamic therapy against periodontally pathogenic bacteria, A. actinomycetemcomitans.MethodsAntibacterial activity of various concentrations of CL extract against A. actinomycetemcomitans was determined. Exponentially growing bacteria were combined with 2-fold dilution of CL extract solution ranging from 25 to 0.098 μg/ml. Co-culture bacteria treated with 0.12% chlorhexidine (CHX) served as the positive control. The effect of photostimulation with light emitting diode (LED) 420–480 nm at 16.8 J/cm² for 1 min on the selected concentration of CL extract was examined. Bacteria viability was determined by plate counting technique. In addition, production of free radicals was tested by electron spin resonance spectroscope (ESR) with 5,5-dimethyl-1-pyrroline N-oxide (DMPO).ResultsThe antibacterial activity of CL extract was dose dependent. Without BL, 25 μg/ml CL extract showed 6.03 ± 0.39 log10A. actinomycetemcomitans. Interestingly, the combination of BL and 0.78 μg/ml CL extract solution showed complete absence of A. actinomycetemcomitans. Peak signal intensity of hydroxyl radical production was also detected with the combination of BL and CL.ConclusionsCL extract not only had antimicrobial activity but also could be used as an effective PS when stimulated with BL in PDT. The optimal antibacterial effect of CL extract with BL was equal to the standard oral disinfectant, 0.12% CHX.



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Enhanced cholinergic-tone during the stress induce a depressive-like state in mice

Publication date: 16 July 2018
Source:Behavioural Brain Research, Volume 347
Author(s): Sara S. Fernandes, André P. Koth, Gustavo M. Parfitt, Marcos F. Cordeiro, Carolina S. Peixoto, Andréa Soubhia, Fernanda P. Moreira, Carolina D. Wiener, Jean P. Oses, Erikson Kaszubowski, Daniela M. Barros
Major depressive disorder has a heterogeneous etiology, since it arises from the interaction of multiple factors and different pathophysiological mechanisms are involved in the symptomatology. This study aimed to investigate the role of the cholinergic system in the susceptibility to stress and, consequently, in the depression-like behavior. C57BL/6 mice were treated with Physostigmine (PHYS), an acetylcholinesterase (AChE) inhibitor, and were submitted to the social defeat stress. For the behavioral evaluation of the locomotor activity, anxiety-like and depression-like behaviors the open field, elevated plus maze, sucrose preference, social interaction and forced swim were used. Hippocampus and prefrontal cortex samples were collected for evaluation of AChE activity, as well as blood samples for analysis of serum cortisol levels. Our results showed that 15 min after the injection of PHYS there was a significant inhibition of AChE activity in the hippocampus and in the prefrontal cortex. On the other hand, in the end of the experimental design, day 12, there was no difference in AChE activity levels. Inhibition of AChE and exposure to the stress led to an increase in cortisol levels. Animals that received PHYS and were exposed to stress showed less social interaction and greater learned helplessness, anhedonia and anxious-like behavior. Taken together, our findings suggest that increasing the cholinergic tone shortly before stress induction impacts on the ability to cope with upcoming stressful situations, leading to a depressive-like state.

Graphical abstract

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Neuroprotective effect of monophosphoryl lipid A, a detoxified lipid A derivative, in photothrombotic model of unilateral selective hippocampal ischemia in rat

Publication date: 16 July 2018
Source:Behavioural Brain Research, Volume 347
Author(s): Sayed Masoud Hosseini, Hamid Gholami Pourbadie, Mohammad Sayyah, Mohammad Ismail Zibaii, Nima Naderi
Finding a neuroprotective strategy to rescue patients suffering from acute brain damage is of great interest. Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) that lacks many of the endotoxic properties of the parent molecule, and yet has similar protective effect. Here, we report the first evidence that MPL preconditioning, similar to LPS preconditioning, can induce neuroprotection against cerebral ischemia. MPL (0.5, 1, 5 μg/rat) was injected unilaterally into the left cerebral ventricle of male rats, and 48 h later, rats were subjected to ipsilateral selective hippocampal ischemia using a modified version of the photothrombotic method. The neuroprotective effects of MPL and LPS were evaluated by measuring infarct size and assessing cognitive function. The expression level of some inflammatory and anti-inflammatory cytokines involving in TLR4 signaling pathway was also measured. Cognitive impairment and infarct size were obvious in control group receiving normal saline intracerebroventricularly and then selective hippocampal ischemia, compared to the sham group. Immunologic preconditioning with MPL or LPS significantly reduced infarct size and improved cognitive function. Additionally, immunologic preconditioning resulted in inflammatory mediators, NF-κB and TNF-α, down-regulation but anti-inflammatory mediators, IRF3, IFN-β, and TGF-β, up-regulation. Our data showed that both MPL and LPS preconditioning may reprogram the TLR4 signaling pathway to produce a cytokine profile which eventually leads to neuroprotection against ischemia injury. MPL, unlike LPS, is safe and well tolerated in clinic, thus it could be considered as a new approach in prevention or even treatment of cerebral ischemic insult consequences.



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Social modulation of risky decision-making in rats (Rattus norvegicus) and tufted capuchin monkeys (Sapajus spp.)

Publication date: 16 July 2018
Source:Behavioural Brain Research, Volume 347
Author(s): F. Zoratto, G. Oddi, E. Gori, A. Micucci, F. De Petrillo, F. Paglieri, W. Adriani, G. Laviola, E. Addessi
Both human and non-human animals frequently deal with risky decisions in a social environment. Nevertheless, the influence of the social context on decision-making has been scarcely investigated. Here, we evaluated for the first time whether the presence of a conspecific influences risk preferences in rats and in tufted capuchin monkeys. Subjects received a series of choices between a constant, safe option and a variable, risky option, both alone (Alone condition) and when paired with a conspecific (Paired condition). The average payoff of the risky option was always lower than that of the safe option. Overall, the two species differed in their attitude towards risk: whereas rats were indifferent between options, capuchins exhibited a preference for the safe option. In both species, risk preferences changed in the Paired condition compared to the Alone condition, although in an opposite way. Whereas rats increased their risk preferences over time when paired with a conspecific, capuchins chose the risky option less in the Paired condition than in the Alone condition. Moreover, whereas anxiety-like behaviours decreased across sessions in rats, these behaviours where more represented in the Paired condition than in the Alone condition in capuchins. Thus, our findings extends to two distantly-related non-human species the evidence, so far available for human beings, that a decrease in anxiety corresponds to an increase in risk preferences, and vice versa. This suggests that the modulation of risk preferences by social influences observed in rats and capuchin monkeys may rely on a common, evolutionarily ancient, mechanism.



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Noisy vestibular stimulation increases gait speed in normals and in bilateral vestibulopathy

Publication date: Available online 10 March 2018
Source:Brain Stimulation
Author(s): Shinichi Iwasaki, Chisato Fujimoto, Naoya Egami, Makoto Kinoshita, Fumiharu Togo, Yoshiharu Yamamoto, Tatsuya Yamasoba
BackgroundGalvanic vestibular stimulation delivered as zero-mean current noise (noisy GVS) has been shown to improve static and dynamic postural stability probably by enhancing vestibular information.Objective/Hypothesis: To examine the effect of an imperceptible level of noisy GVS on dynamic locomotion in normal subjects as well as in patients with bilateral vestibulopathy.MethodsWalking performance of 19 healthy subjects and 12 patients with bilateral vestibulopathy at their preferred speed was examined during application of noisy GVS with an amplitude ranging from 0 to 1000 μA. The gait velocity, stride length and stride time were analyzed.ResultsNoisy GVS had significant effects on gait velocity, stride length and stride time in healthy subjects as well as in patients with bilateral vestibulopathy (p < 0.05). The optimal amplitude of noisy GVS improved gait velocity by 10.9 ± 1.2%, stride length by 5.7 ± 1.2% and stride time by 4.6 ± 7% (p < 0.0001) compared to the control session in healthy subjects. The optimal stimulus improved gait velocity by 12.8 ± 1.3%, stride length by 8.3 ± 1.1% and stride time by 3.7 ± 7% (p < 0.0001) in patients with bilateral vestibulopathy. The improved values of these parameters of locomotion by noisy GVS in the patients were not significantly different from those in healthy subjects in the control condition (p > 0.4).ConclusionNoisy GVS is effective in improving gait performance in healthy subjects as well as in patients with bilateral vestibulopathy.



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Distribution of pituitary adenylate cyclase-activating polypeptide 2 in zebrafish brain

Publication date: Available online 10 March 2018
Source:Peptides
Author(s): Tomoya Nakamachi, Eri Kamata, Ayano Tanigawa, Norifumi Konno, Seiji Shioda, Kouhei Matsuda
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide with an amino acid sequence that is well conserved among vertebrates. In teleosts, including zebrafish, the PACAP gene (adcyap1) has been duplicated to yield adcyap1a (coding PACAP1) and adcyap1b (coding PACAP2). This study aims to determine the distribution of these PACAPs and their mRNAs in zebrafish. We generated a zebrafish PACAP2-specific antibody. Using real-time PCR, we observed that adcyap1b mRNA was primarily localized in the brain, with the highest level in the telencephalon, followed by the diencephalon. Using immunostaining of brain tissue samples, PACAP2 immunoreactivity was observed mainly in the telencephalon, hypothalamus, and cerebellum, and the immunopositive fibers formed a line to the habenula. PACAP2-immunopositive cells were observed in the ventral and dorsal regions of the telencephalon and in the hypothalamic nucleus of the diencephalon in the colchicine-injected brain. This distribution of PACAP2 suggests its involvement in higher brain functions in teleosts, such as learning and cognition, as well as instinctive behaviors such as feeding and emotional regulation.



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Identification of evolutionarily conserved residues required for the bioactivity of a pedal peptide/orcokinin-type neuropeptide

Publication date: Available online 10 March 2018
Source:Peptides
Author(s): Chan-Hee Kim, Hye-Jin Go, Hye Young Oh, Maurice R. Elphick, Nam Gyu Park
Pedal peptides and orcokinins are structurally related neuropeptides that were first discovered in protostomian invertebrates − mollusks and arthropods, respectively. Recently, pedal peptide/ocokinin (PP/OK)-type neuropeptides were discovered in a deuterostomian phylum, the echinoderms, indicating that the evolutionary origin of this neuropeptide family can be traced back to the common ancestor of bilaterian animals. Sequences comparison of PP/OK-type neuropeptides reveals several conserved residues, including N- and C-terminally located hydrophobic residues that are important for the bioactivity of orcokinin. Here we report the first comprehensive analysis of the structure-activity relationships of a PP/OK-type neuropeptide − starfish myorelaxant peptide (SMP; FGKGGAYDPLSAGFTD) from the starfish Patiria pectinifera (Phylum Echinodermata). Comparison of the bioactivity of SMP with N-terminally and/or C-terminally truncated and alanine-substituted SMP analogs revealed a core peptide (GAYDPLSAGF; SMP(5-14)) that retains the muscle-relaxing activity of SMP, albeit with reduced potency and efficacy. Within this core peptide, alanine-substitution of several residues resulted in complete or partial loss of bioactivity, whilst loss or substitution of the N-terminal phenylalanine residue of SMP also caused a substantial reduction in bioactivity. Furthermore, analysis of the bioactivity of other SMP-like peptides derived from the same precursor as SMP revealed that none of these were more potent/effective than SMP as muscle relaxants. In conclusion, we have identified key residues required for the bioactivity of a PP/OK-type neuropeptide (SMP), including hydrophobic residues located in the N- and C-terminal regions that are conserved in PP/OK-type peptides from other phyla as well as core residues that are conserved in echinoderm PP/OK-type peptides.

Graphical abstract

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The Impact of Gadolinium Deposition on Radiology Practice: An International Survey of Radiologists

Publication date: Available online 7 February 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Ryan T. Fitzgerald, Vikas Agarwal, Jenny K. Hoang, Frank Gaillard, Andrew Dixon, Emanuel Kanal
Rationale and ObjectivesBrain deposition of gadolinium following the administration of gadolinium-based contrast agents (GBCAs) was initially reported in 2014. Gadolinium deposition is now recognized as a dose-dependent consequence of exposure. The potential clinical implications are not yet understood. The purpose of this study was to determine radiologists' reporting practices in response to gadolinium deposition.Materials and MethodsAn electronic survey querying radiologists' practices regarding gadolinium deposition was distributed by Radiopaedia.org from November-December 2015.ResultsOur study sample included 94 total respondents (50% academic; 27% private practice; 23% hybrid) from 30 different countries (USA 18%). Fifty-seven (62%) radiologists had observed brain gadolinium deposition on MRI brain studies howerver more than half of these (30 of 57) reported detecting dentate T1 shortening only rarely (<1/month). Among respondents, 58% (52 of 89) do not or would not include the finding in the radiology report; only 12 (13%) report the finding in the impression of their reports. The most common reason for not reporting gadolinium deposition was the risk of provoking unnecessary patient anxiety (29%, 20 of 70). Recent data on gadolinium deposition has led to a reported practice change in 24 of 87 (28%) of respondents.ConclusionRecognition of, and attitudes toward, brain gadolinium deposition were inconsistent in this worldwide sample. Most surveyed radiologists do not routinely report dentate T1shortening as a marker of gadolinium deposition. Fear of provoking patient/clinician anxiety and an incomplete understanding of the implications of gadolinium deposition contribute to inconsistencies in reporting.



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The Relationship between Posttraumatic and Depressive Symptoms during Virtual Reality Exposure Therapy with a Cognitive Enhancer

Publication date: Available online 10 March 2018
Source:Journal of Anxiety Disorders
Author(s): Melissa Peskin, Katarzyna Wyka, Judith Cukor, Megan Olden, Margaret Altemus, Francis S. Lee, JoAnn Difede
Two studies suggest that reductions in posttraumatic symptoms (Aderka et al., 2013) and cognitions (Zalta et al., 2014) precede reductions in depressive symptoms during prolonged exposure (PE) therapy for posttraumatic stress disorder (PTSD) in female assault survivors. The present study explored the temporal relationship between posttraumatic and depressive symptoms in a randomized trial of D-Cycloserine (DCS) versus placebo augmented virtual reality exposure (VRE) therapy for chronic World Trade Center-related PTSD following the September 11, 2001 terrorist attacks. Twenty-five male and female participants were randomly assigned to receive either 100 mg DCS (N = 13) or placebo (N = 12) 90 minutes before 12 weekly VRE sessions. Participants contributed a total of 280 weekly PTSD Checklist (PCL; Weathers et al., 1993) and Beck Depression Inventory-second edition (BDI-II; Beck et al., 1996) symptom scores. Two sets of mediation analyses for longitudinal mixed models assessed the effects of 1) lagged PCL on BDI-II (Model 1), and 2) lagged BDI-II on PCL (Model 2) in the VRE-DCS and VRE-Placebo treatment groups, respectively. Results revealed reciprocal relations between posttraumatic and depressive symptoms during VRE treatment, although reductions in posttraumatic symptoms led to subsequent reductions in depressive symptoms to a greater extent than the converse. These effects were stronger in the DCS-enhanced group. Findings suggest that VRE primarily decreases posttraumatic symptoms, which in turn leads to decreased depressive symptoms, and that DCS may strengthen these effects.



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High-performance for hydrogen evolution and pollutant degradation of reduced graphene oxide/two-phase g-C 3 N 4 heterojunction photocatalysts

Abstract

We have successfully synthesized the composites of two-phase g-C₃N₄ heterojunction photocatalysts by one-step method. And the reduced graphene oxide/two-phase g-C₃N₄ heterojunction photocatalyst was fabricated via a facile hydrothermal reduction method. The characterization results indicated that the two-phase g-C₃N₄ was integrated closely, and the common phenomenon of agglomeration for g-C₃N₄ was significantly reduced. Moreover, the oxidized graphene was reduced successfully in the composites and the graphene was overlaid on the surface or the interlayers of g-C₃N₄ heterojunction composite uniformly. In addition, we have carried out the photocatalytic activity experiments by H₂ evolution and rhodamine B removal, tetracycline removal under the visible light irradiation. The results revealed that the composite has improved the separation efficiency a lot than the pure photocatalyst. The photocurrent test demonstrated that the recombination of electrons and holes were efficiently inhibited as well as enhanced the photocatalytic activity. The 0.4% rGO loaded samples, 0.4% rGOCN2, own the best performance. Its rate of H₂ evolution was 15 times as high as that of the pure g-C₃N₄.

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The regulatory role of endogenous iron on greenhouse gas emissions under intensive nitrogen fertilization in subtropical soils of China

Abstract

Anaerobic batch experiments were conducted to study the regulatory role of endogenous iron in greenhouse gas emissions under intensive nitrogen fertilization in subtropical soils of China. Fe²⁺, Fe³⁺, and NO₃⁻-N dynamics and N₂O, CH₄, and CO₂ emissions, as well as the relationships between N fertilizer, endogenous iron, and greenhouse gas emissions were investigated. The emissions of N₂O increased to different extents from all the test soils by N1 (260 mg N kg⁻¹) application compared with N0. After 24 days of anaerobic incubation, the cumulative emissions of N₂O from red soils in De'an (DR) were significantly higher than that from paddy soils in De'an (DP) and Qujialing (QP) under N1. However, N application enhanced CH₄ and CO₂ emissions from the red soils slightly but inhibited the emissions from paddy soils. The maximal CH₄ and CO₂ emission fluxes occurred in DP soil without N input. Pearson's correlation analysis showed that there were significant correlations (P < 0.01) between Fe²⁺ and Fe³⁺, NO₃⁻-N, (N₂O + N₂)-N concentrations in DP soil, implying that Fe²⁺ oxidation was coupled with nitrate reduction accompanied by (N₂O + N₂)-N emissions and the endogenous iron played a regulatory role in greenhouse gas emissions mainly through the involvement in denitrification. The proportion of the electrons donated by Fe²⁺ used for N₂O production in denitrification in DP soil was approximately 37.53%. Moreover, positive correlations between Fe²⁺ and CH₄, CO₂ were found in both DR and QP soils, suggesting that endogenous iron might regulate the anaerobic decomposition of organic carbon to CH₄ and CO₂ in the two soils. Soil pH was also an important factor controlling greenhouse gas emissions by affecting endogenous iron availability and C and N transformation processes.

http://ift.tt/2HpqR2J

Growth and nutrition of Agelastica coerulea (Coleoptera: Chrysomelidae) larvae changed when fed with leaves obtained from an O 3 -enriched atmosphere

Abstract

A series of laboratory no-choice assays were performed to test changes in the feeding, growth, and nutrition of leaf beetle (Agelastica coerulea) larval instars on O₃-treated leaves of Japanese white birch (Betula platyphylla var. japonica). Larvae fed with O₃-treated leaves grew and developed significantly faster throughout their developmental cycle than the corresponding controls. The growth rate (GR) and consumption index (CI) were mostly decreased with age for both control and O₃-treated leaves. Efficiency of conversion of both ingested and digested food (ECI, ECD) showed an increase from the 2nd to the 4th instar, after which they decreased significantly and reached the lowest value in the last larval instars (7th). GR, CI, ECI, and ECD were greater and approximate digestibility (AD) was lower in larvae fed with O₃-treated leaves than those fed with control leaves. This indicated that the greater rate of growth on fumigated leaves was due primarily to a greater rate of consumption (i.e., O₃ increased the "acceptability" of the host more than "suitability") and efficiency in converting food into body mass. Overall, larval performance seemed to have improved when fed with O₃-treated leaves in these assays. This study suggests that insects may be more injurious to O₃-treated plants and warrants further investigations on birch-beetle interactions under field conditions.

http://ift.tt/2GeQ00F

Study on turbulence characteristics and sensitivity of quadrant analysis to threshold level in Lake Taihu

Abstract

The identification of coherent structures is very important in investigating the sediment transport mechanism and controlling the eutrophication in shallow lakes. This study analyzed the turbulence characteristics and the sensitivity of quadrant analysis to threshold level. Simultaneous in situ measurements of velocities and suspended sediment concentration (SSC) were conducted in Lake Taihu with acoustic Doppler velocimeter (ADV) and optical backscatter sensor (OBS) instruments. The results show that the increase in hole size makes the difference between dominant and non-dominant events more distinct. Wind velocity determines the frequency of occurrence of sweep and ejection events, which provide dominant contributions to the Reynolds stress. The increase of wind velocity enlarges the magnitude of coherent events but has little impact on the events frequency with the same hole size. The events occurring within short periods provide large contributions to the momentum flux. Transportation and diffusion of sediment are in control of the intermittent coherent events to a large extent.

http://ift.tt/2HmxjaG

Reducing X-Ray imaging for proton postmastectomy chest-wall patients

Publication date: Available online 10 March 2018
Source:Practical Radiation Oncology
Author(s): Estelle Batin, Nicolas Depauw, Rachel B. Jimenez, Shannon MacDonald, Hsiao-Ming Lu




http://ift.tt/2oWTZrm

Renal Cell Carcinoma Brain Metastasis with Pseudoprogression and Radiation Necrosis on Nivolumab after previous treatment with Stereotactic Radiosurgery: an Illustrative Case Report and Review of the Literature

Publication date: Available online 10 March 2018
Source:Practical Radiation Oncology
Author(s): Gary D. Lewis, Eric Jonasch, Amishi Shah, Gregory N. Fuller, Andrew M. Farach, E. Brian Butler, Bin S. Teh




http://ift.tt/2DiNC5I

Biomaterial scaffolds for non-invasive focal hyperthermia as a potential tool to ablate metastatic cancer cells

Publication date: June 2018
Source:Biomaterials, Volume 166
Author(s): Francisco Pelaez, Navid Manuchehrabadi, Priyatanu Roy, Harishankar Natesan, Yiru Wang, Emilian Racila, Heather Fong, Kevin Zeng, Abby M. Silbaugh, John C. Bischof, Samira M. Azarin
Currently, there are very few therapeutic options for treatment of metastatic disease, as it often remains undetected until the burden of disease is too high. Microporous poly(ε-caprolactone) biomaterials have been shown to attract metastasizing breast cancer cells in vivo early in tumor progression. In order to enhance the therapeutic potential of these scaffolds, they were modified such that infiltrating cells could be eliminated with non-invasive focal hyperthermia. Metal disks were incorporated into poly(ε-caprolactone) scaffolds to generate heat through electromagnetic induction by an oscillating magnetic field within a radiofrequency coil. Heat generation was modulated by varying the size of the metal disk, the strength of the magnetic field (at a fixed frequency), or the type of metal. When implanted subcutaneously in mice, the modified scaffolds were biocompatible and became properly integrated with the host tissue. Optimal parameters for in vivo heating were identified through a combination of computational modeling and ex vivo characterization to both predict and verify heat transfer dynamics and cell death kinetics during inductive heating. In vivo inductive heating of implanted, tissue-laden composite scaffolds led to tissue necrosis as seen by histological analysis. The ability to thermally ablate captured cells non-invasively using biomaterial scaffolds has the potential to extend the application of focal thermal therapies to disseminated cancers.

Graphical abstract

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“Stepwise Extraction” strategy-based injectable bioresponsive composite implant for cancer theranostics

Publication date: June 2018
Source:Biomaterials, Volume 166
Author(s): Bowen Yang, Han Lin, Chen Dai, Yu Chen, Jianlin Shi
"Smart" bioresponsive materials, which are sensitive to biological signals or pathological abnormalities, are appealing therapeutic platforms for the development of next-generation cancer theranostics. In this work, a novel "stepwise extraction" strategy has been proposed and demonstrated in constructing injectable bioresponsive composite implant, which features unique theranostic responsivenesses to exogenous and external triggers. The as-designed implant exhibits theranostic functions and biodegradability for cancer treatment based on the change of intratumoral microenvironment and the needs of therapeutic process. This "stepwise extraction" process, that is, "solvent extraction", "manganese extraction" and "phosphorus extraction", significantly promoted the biodegradation and disintegration of the bioresponsive implant step by step, accompanied by the corresponding component releases from the PLGA framework and furthermore, accomplished different specific theranostic functions needed at different treatment stages. This is the first demonstration of bioresponsive organic-inorganic hybrid implant with marked theranostic functions and excellent biodegradability by a "stepwise extraction" approach, paving the way to the solutions of unsatisfactory therapeutic efficacy and strong side effects in current cancer therapeutic modalities.

Graphical abstract

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Nitrite exerts antioxidant effects, inhibits the mTOR pathway and reverses hypertension-induced cardiac hypertrophy

Publication date: Available online 9 March 2018
Source:Free Radical Biology and Medicine
Author(s): Danielle A. Guimaraes, Madla A. dos Passos, Elen Rizzi, Lucas C. Pinheiro, Jefferson H. Amaral, Raquel F. Gerlach, Michele M. Castro, Jose E. Tanus-Santos
Cardiac hypertrophy is a common consequence of chronic hypertension and leads to heart failure and premature death. The anion nitrite is now considered as a bioactive molecule able to exert beneficial cardiovascular effects. Previous results showed that nitrite attenuates hypertension-induced increases in reactive oxygen species (ROS) production in the vasculature. Whether antioxidant effects induced by nitrite block critical signaling pathways involved in cardiac hypertrophy induced by hypertension has not been determined yet. The Akt/mTOR signaling pathway is responsible to activate protein synthesis during cardiac remodeling and is activated by increased ROS production, which is commonly found in hypertension. Here, we investigated the effects of nitrite treatment on cardiac remodeling and activation of this hypertrophic signaling pathway in 2 kidney-1 clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral nitrite at 1 or 15mg/kg for four weeks. Nitrite treatment (15mg/kg) reduced systolic blood pressure and decreased ROS production in the heart tissue from hypertensive rats. This nitrite dose also blunted hypertension-induced activation of mTOR pathway and cardiac hypertrophy. While the lower nitrite dose (1mg/kg) did not affect blood pressure, it exerted antioxidant effects and tended to attenuate mTOR pathway activation and cardiac hypertrophy induced by hypertension. Our findings provide strong evidence that nitrite treatment decreases cardiac remodeling induced by hypertension as a result of its antioxidants effects and downregulation of mTOR signaling pathway. This study may help to establish nitrite as an effective therapy in hypertension-induced cardiac hypertrophic remodeling.

Graphical abstract

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Nrf2 inhibits oxaliplatin-induced peripheral neuropathy via protection of mitochondrial function

Publication date: Available online 9 March 2018
Source:Free Radical Biology and Medicine
Author(s): Yang Yang, Lan Luo, Xueting Cai, Yuan Fang, Jiaqi Wang, Gang Chen, Jie Yang, Qian Zhou, Xiaoyan Sun, Xiaolan Cheng, Huaijiang Yan, Wuguang Lu, Chunping Hu, Peng Cao
Oxaliplatin-induced peripheral neuropathy (OIPN) is a severe, dose-limiting toxicity associated with cancer chemotherapy. The efficacy of antioxidant administration in OIPN is debatable, as the promising preliminary results obtained with a number of antioxidants have not been confirmed in larger clinical trials. Besides its antioxidant activity, the transcription factor, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2 (Nrf2) plays a crucial role in the maintenance of mitochondrial homeostasis, and mitochondrial dysfunction is a key contributor to OIPN. Here, we have investigated the protective properties of Nrf2 in OIPN. Nrf2^-/- mice displayed severe mechanical allodynia and cold sensitivity and thus experienced increased peripheral nervous system injury compared to Nrf2^+/+ mice. Furthermore, Nrf2 knockout aggravated oxaliplatin-induced reactive oxygen species production, decreased the mitochondrial membrane potential, led to abnormal intracellular calcium levels, and induced cytochrome c-related apoptosis and overexpression of the TRP protein family. Sulforaphane-induced activation of the Nrf2 signaling pathway alleviated morphological alterations, mitochondrial dysfunction in dorsal root ganglion neurons, and nociceptive sensations in mice. Our findings reveal that Nrf2 may play a critical role in ameliorating OIPN, through protection of mitochondrial function by alleviating oxidative stress and inhibiting TRP protein family expression. This suggests that pharmacological or therapeutic activation of Nrf2 may be used to prevent or slow down the progression of OIPN.

Graphical abstract

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Simultaneous oxidation of Hg 0 and NH 3 -SCR of NO by nanophase Ce x Zr y Mn z O 2 at low temperature: the interaction and mechanism

Abstract

Simultaneous oxidation of Hg⁰ and NH₃-SCR of NO by catalyst is one of the key methods for co-purification of coal-fired flue gas. Till now, the interaction between the oxidation of Hg⁰ and NH₃-SCR of NO and its mechanism have not clarified. In this study, a series of nanophase Ce_x Zr_y Mn_z O₂ was prepared for the simultaneous oxidation of Hg⁰ and NH₃-SCR of NO at low temperature. The catalysts were characterized using surface area analysis, X-ray diffraction, temperature-programmed techniques, and several types of microscopy and spectroscopy. The experimental results indicated that the Ce_0.47Zr_0.22Mn_0.31O₂ exhibited superior Hg⁰ removal efficiency (> 99%) and NO conversion efficiency (> 90%) even at 150 °C, and it also exhibited a good durability in the presence of SO₂ and H₂O. The excellent performance of Ce_0.47Zr_0.22Mn_0.31O₂ on co-purifying Hg⁰ and NO was due to the stronger synergistic effects of Ce-Zr-Mn in Ce_0.47Zr_0.22Mn_0.31O₂ than that of the others, which was illustrated by the characterization results of XPS, XRD, and FT-IR. Moreover, it was found that the NO conversion of Ce_0.47Zr_0.22Mn_0.31O₂ could be slightly influenced by Hg⁰ and was decreased about 4% to the max, while that of Hg⁰ could rarely be affected by the selected catalytic reduction process of NO. It might be due to the co-purification mechanism of NO and Hg⁰. The mechanism of the simultaneous oxidation of Hg⁰ and NH₃-SCR of NO was mainly due to the synergetic effect on the mobility of surface oxygen and the activation of lattice oxygen of Ce_0.47Zr_0.22Mn_0.31O₂. The effect of the oxidation of Hg⁰ on the NH₃-SCR of NO was mainly due to the absorbed Hg⁰/Hg²⁺ on the surface of Ce_0.47Zr_0.22Mn_0.31O₂, which attenuated the formation of NH_3(ad), −NH_2(ad), and NH₄⁺ on its acid sites. Similarly, the NH₃-SCR of NO process could hardly influence the oxidation of Hg⁰ when NO and Hg⁰ were co-purified.

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