Correlation between alpha phase morphology and tensile properties of a new beta titanium alloy

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): S. Sadeghpour, S.M. Abbasi, M. Morakabati, S. Bruschi
A novel beta titanium alloy Ti-4Al-7Mo-3Cr-3V (Ti-4733) was developed and the effect of its microstructure on the tensile properties was investigated and compared with the one of the commercial titanium alloy Ti-5553. Various alpha phase morphologies, namely globular, lamellar, acicular and a combination of them, were obtained as a result of the various heat treatments to which both the alloys were subjected. Although the alpha phase morphology for a given heat treatment was similar in both the alloys, the obtained microstructure was generally finer in the Ti-4733 alloy than in the Ti-5553 alloy, leading to enhanced tensile properties. The results showed that the microstructures with solely fine acicular alpha precipitates exhibited the highest tensile strength. While the highest reduction of area was derived in case of globular-acicular morphology, the maximum elongation was observed in microstructures containing lamellar-acicular alpha phase. Furthermore, for both the alloys the best balance between strength and ductility occurred in microstructures with a combination of globular and acicular alpha phase. The fractography analysis carried out on the tensile tested specimens showed a completely ductile fracture in case of globular-acicular morphology, ductile-transgranular brittle for lamellar-acicular morphology, and ductile-intergranular brittle for fully acicular α phase morphology.

Graphical abstract

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Effect of replacement of silica fume with calcined clay on the hydration and microstructural development of eco-UHPFRC

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Wei Huang, Hadi Kazemi-Kamyab, Wei Sun, Karen Scrivener
In this paper, the replacement of high cost silica fume with calcined clay was investigated in UHPFRC mixes. The impact of two grades of calcined clay on the hydration and microstructural development of UHPFRC matrices was investigated, where 54% of the cement by volume has already been replaced by a limestone with similar PSD. It was seen that comparable mixes were obtained when silica fume was replaced with calcined clay by volume. The experimental results revealed a competition for water between the cement hydration and pozzolanic reaction of kaolinite to form more AFt and AFm phases, which affected the compressive strength development of the UHPFRC matrices. This competition is more pronounced in mixes where the kaolinite content increases in the calcined clay.

Graphical abstract

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Facile synthesis of Fe3O4@PPy core-shell magnetic nanoparticles and their enhanced dispersity and acid stability

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Shun Tang, Qian Lan, Jiyuan Liang, Shengrui Chen, Chang Liu, Jinxing Zhao, Qi Cheng, Yuan-Cheng Cao, Jiyan Liu
We report a facile method to synthesize polypyrrole-coated Fe3O4 core-shell magnetic nanoparticles (Fe3O4@PPy). First, crude Fe3O4 nanoparticles were synthesized by co-precipitation approach. PPy layers were generated and deposited on the surface of Fe3O4via in-situ electropolymerization and electrodeposition, to construct core-shell structure nanoparticles. TEM observations showed the Fe3O4 nanoparticles changed from 15nm to 120nm in diameter after the PPy coating. The composition and morphology of Fe3O4@PPy nanoparticles were characterized by advanced spectroscopic and imaging techniques. The Fe3O4@PPy nanoparticles possess good dispersion property and acid stability in strong acid aqueous. The magnetic measurement at room temperature indicates that the Fe3O4@PPy nanoparticles exhibit superparamagnetic behavior, holding the saturation magnetization of 43.5emu/g. All the results show great potentials of the Fe3O4@PPy nanoparticles in wide range of applications.

Graphical abstract

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In situ analysis of the crystallization process of Sb2S3 thin films by Raman scattering and X-ray diffraction

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Romain Parize, Thomas Cossuet, Odette Chaix-Pluchery, Hervé Roussel, Estelle Appert, Vincent Consonni
Sb2S3 thin films grown by chemical bath deposition have received increasing interest for its integration into solar cells. However, its crystallization by post-deposition annealing represents a major difficulty owing to its instability at relatively low temperature. We combine in situ Raman scattering at very low laser power with in situ X-ray diffraction over a broad range of annealing temperatures and durations under N2 atmosphere to elucidate its crystallization process on anatase-TiO2 layers. The thermally activated crystallization is found to systematically involve the intermediate formation of a metallic Sb phase and very often of a senarmontite cubic Sb2O3 phase, both of them vanishing prior to the formation of the stibnite Sb2S3 phase. Compact and continuous 150nm-thick Sb2S3 thin films with no pyramid-shaped clusters on their top surface are crystallized in the range of 240 to 270°C, namely below the commonly used annealing temperature of 300°C. Their texture is tunable from (420) and (520) to (020) and (200) planes parallel to the surface by raising the annealing temperature owing to a process of abnormal grain growth. The Sb2S3 thin films crystallized at the optimal annealing temperature of 270°C are composed of dense crystallites with a typical size of several tens of nanometers, which is of high interest for their integration into solar cells.

Graphical abstract

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Structure and electrical properties of pure and yttrium-doped HfO2 films by chemical solution deposition through layer by layer crystallization process

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Hailong Liang, Jin Xu, Dayu Zhou, Xuexia Wang, Xiaohua Liu, Shichao Chu, Xiaoying Liu
Pure and yttrium doped HfO2 thin films were fabricated on Si (100) substrates by chemical solution deposition through a layer by layer crystallization process. We systematically investigated the effects of thickness and Y doped concentration on structure and electrical properties of the HfO2 films. Results revealed that 4nm thick undoped HfO2 was crystallized into a t/c-phase due to the surface energy effect, and this higher symmetry phase could be retained up to a film thickness of 16nm through the layer by layer crystallization process. This layer by layer crystallization process also required less Y doping to stabilize t/c-HfO2 in thick films. The films showed a high dielectric constant about 42, low leakage current density of about 10⁻⁷A/cm² (at 1MV/cm) and a breakdown field up to 5MV/cm. Considering the cost-effective deposition technique and good electrical properties, these films would be suitable for insulator applications in microelectronic devices.

Graphical abstract

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The interplay between morphology and photocatalytic activity in ZnO and N-doped ZnO crystals

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Gabriela Byzynski, Camila Melo, Diogo P. Volanti, Mateus M. Ferrer, Amanda F. Gouveia, Cauê Ribeiro, Juan Andrés, Elson Longo
Intrinsic characteristics of the material such as superficial area, morphological structure, and crystalline phase exposition play a fundamental role in the corresponding reaction paths. However, especially in doped semiconductors, as ZnO:N, less is known about how the synthesis parameters affect the morphologies and the photocatalytic activity simultaneously. To solve this issue, ZnO and ZnO:N samples were obtained using microwave-assisted hydrothermal and modified polymeric precursor methods of synthesis. Samples morphologies were characterized by TEM and FE-SEM. Crystallographic phases were observed by XRD and optical characteristics by DRS. XPS results confirmed the doping process. Degradation of Rhodamine-B and Cr(VI) reduction were employed as probe reactions to investigate their photocatalytic activity. Although the crystallographic structure of these powders maintains the ZnO hexagonal wurtzite structure, the optical properties, morphologies, and photocatalytic activities present different behaviors. Also, density functional theory calculations were employed to determine the specific features related to electronic structure, morphology, and photocatalytic activity. Different synthesis methods produce a singular behavior in the physicochemical properties of materials, and the doping effect produces various modifications in RhB degradation and Cr(VI) reduction for each synthesis method. Crystal face exposition and morphologies are related to the improvement in the photocatalytic activity of the materials.

Graphical abstract

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Tyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): AE El-Shazly, P Roncarati, M Lejeune, PP Lefebvre, P Delvenne
We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation.Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR.



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Antioxidant activity and protective effect of suramin against oxidative stress in collagen induced arthritis

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Debasis Sahu, Shikha Sharma, Rajeev K. Singla, Amulya Kumar Panda
It is imperative to interrupt the link between arthritis and regulation of oxidative stress with the administration of antioxidants. Suramin is known for its anti-inflammatory, antineoplastic and antiangiogenic activities implying its possible antioxidant property. In this study, the antioxidant activity of suramin in cell free system was found to be higher than l-ascorbic acid (l-AA) with respect to its scavenging effect on nitric oxide (NO), hypochlorous acid and hydrogen peroxide radicals. Besides, suramin was found to be nontoxic to cultured RAW cells even at high concentrations along with marked inhibition of NO production. Suramin was found to curb the inflammation associated with the collagen induced arthritis (CIA) model. Administration of suramin significantly reduced the malondialdehyde and protein carbonyl content in joints, liver, kidney and spleen of rats as studied ex vivo. Furthermore, the increased antioxidant enzymes such as SOD, catalase, GST, GPx and GR activities in the tissues were restored significantly after suramin treatment. In silico experiments using Vlife MDS4.4-GRIP docking method showed strong affinity of suramin towards erythrocyte catalase followed by glutathione peroxidase thus corroborating with the findings of antioxidant enzyme assays. Our studies clearly indicate that suramin has remarkable antioxidant potential and can ameliorate arthritis via modulation of oxidative stress.

Graphical abstract

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Multifunctional LUV liposomes decorated for BBB and amyloid targeting. A. In vitro proof-of-concept

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Konstantina Papadia, Eleni Markoutsa, Spyridon Mourtas, Anastassios D. Giannou, Barabara La Ferla, Fransesco Nicotra, Mario Salmona, Pavlos Klepetsanis, Georgios T. Stathopoulos, Sophia G. Antimisiaris
Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential. Likewise, mf-LIP inhibitory effect on Aβ aggregation was similar to that of LIPs functionalized only with TREG, proving that the presence of brain targeting ligands does not reduce the functionality of the amyloid-specific ligand. Addition of the curcumin-lipid in some liposome types was found to enhance their integrity and reduce the effect of serum proteins on their interaction with brain endothelial cells. Finally, preliminary in vivo results confirm the in vitro findings. Concluding, the current results reveal the potential of the specific curcumin-lipid derivative as a component of multifunctional LIPs with efficient brain targeting capability, intended to act as a theragnostic system for AD.

Graphical abstract

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Potential of amphiphilic graft copolymer α-tocopherol succinate-g-carboxymethyl chitosan in modulating the permeability and anticancer efficacy of tamoxifen

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Sunil K. Jena, Sanjaya K. Samal, Shamandeep Kaur, Mahesh Chand, Abhay T. Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3.8-fold when incorporated into Cmc-TS PMs. Cytotoxicity of Cmc-TS PMs was studied on MCF-7 cell line by MTT and; confocal microscopy was used for cellular uptake. Confocal microscopy revealed that Cmc-TS PMs could effectively accumulate in the cytosol of MCF-7 cell lines. In vitro data was further validated using N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model in Sprague-Dawley rats. Hepatotoxicity profiles of TMX-PMs at three different doses were also evaluated against the free drug TMX. TMX-PMs were more effective in suppressing breast tumor in MNU-induced mammary carcinoma model than free TMX with better safety profile. In addition, histological data shows that tumors are "benign" in TMX-PMs treated group compared with "malignant" tumors in free TMX treated and control groups. Overall, the results implicate that our Cmc-TS PMs may serve as a promising carrier for the intracellular delivery of anticancer drug molecules via oral route.

Graphical abstract

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Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Marko Krstić, Marija Radojević, Dušica Stojanović, Vesna Radojević, Petar Uskoković, Svetlana Ibrić
The preparation and characterization of films and nanofibers with carvedilol as a poorly water-soluble drug in poly (ethylene oxide) (PEO) polymer were investigated. Films are prepared by solution casting method, and nanofibers by electrospinning from a polymer solution. Water and mixture of ethanol and water were used as solvents. FT-IR analysis of the samples showed that there was no interaction between the polymer and the drug substance. DSC analysis revealed that carvedilol was dissolved in the polymer and influenced the degree of crystallinity of PEO. Carvedilol release rate for all of the formulations was increased in comparison with pure carvedilol. Significant differences in the rate of release of carvedilol from the films and nanofibers were observed. Field Emission Scanning Electron Microscope (FESEM) images of the obtained fiber was revealed the dependence of the fiber diameter of formulation and electrospinning process parameters, and consequently influence the amount and distribution of carvedilol in the encapsulated fibers.

Graphical abstract

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Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Nika Bahari Javan, Hamed Montazeri, Leila Rezaie Shirmard, Nersi Jafary Omid, Ghullam Reza Barbari, Mohsen Amini, Mohammad Hossein Ghahremani, Morteza Rafiee-Tehrani, Farid Abedin Dorkoosh
In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins.

Graphical abstract

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Screening of inhibitors of angiotensin-converting enzyme (ACE) employing high performance liquid chromatography-electrospray ionization triple quadrupole mass spectrometry (HPLC-ESI-QqQ-MS)

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Syed Ghulam Musharraf, Muhammad Salman Bhatti, Muhammad Iqbal Choudhary, Atta-ur Rahman
Angiotensin-converting enzyme (ACE) plays a key role in regulating blood pressure in the body by converting the angiotensin I (AI) into angiotensin II (AII). Angiotensin II is a potent vaso-active peptide that causes arterioles to constrict, resulting in increased blood pressure. A rapid and sensitive method for the identification of inhibitors of ACE was developed, and optimized employing HPLC-ESI-QqQ-MS. In this assay, angiotensin I substrate was converted into the product angiotensin II with the catalytic action of ACE. A calibration curve for depleting concentration of angiotensin I was developed and linearity of R²=0.999 with a remarkably low concentration of substrate range 20–200nM. The limit of detection and quantification of angiotensin I was found to be 1.93 and 5.84nM, respectively. The enzymatic reaction was optimized for incubation time, concentration, and volume of enzyme and substrate. All reactions were performed at 37°C at pH7.5 with standard incubation time of 20min. Two standard inhibitors, Captopril and Lisinopril, were checked through the newly developed method for their inhibitory potential, and their IC50 values were found to be 3.969 and 0.852μM, respectively. Reproducibility and precision analysis of different experiments showed <9.9% RSD. The developed method can be used for the identification of new ACE inhibitors.

Graphical abstract

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Optimization of paeonol-loaded poly(butyl-2-cyanoacrylate) nanocapsules by central composite design with response surface methodology together with the antibacterial properties

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Jingjing Yao, Yangxin Zhang, Qiming Hu, Decheng Zeng, Fang Hua, Wei Meng, Weiyun Wang, Guan-Hu Bao
With the aim to enhance dissolution rate and bioavailability of paeonol, paeonol-loaded poly(butyl-2-cyanoacrylate) nanocapsules (Pae@PNCs) were prepared by interfacial spontaneous polymerization for the first time. Herein, a rotatable central composite design (RCCD) with three-factor five-level was applied to evaluate the optimization experiments. To the maximum percentage encapsulation efficiency (EE%) and minimum particle size (nm) of the Pae@PNCs, a quadratic polynomial model was generated to predict and evaluate the independent variables with respect to the dependent variables. RSM model goodness fitting were confirmed by the ANOVA Table (P<0.05) through variance analysis, which predicted values of EE (%) and particle size (R² and adjusted R² were close to 1, respectively) in good agreement with experimental values. By solving the regression equation and analyzing the response surface, three-dimensional model graphs and plots, the optimal result for the preparation of Pae@PNCs were found to be: pH (2.34), Poloxamer F-68 (0.80% m/v) and ethyl acetate/α-BCA ratio (16.67 v/v) for the highest EE% (73.58±2.76%) and the smallest particle size (42.06±1.20nm). The release profiles and antibacterial activity in vitro from the optimal Pae@PNCs were performed. The results indicated that it has slow and well-controlled release, and has strong antibacterial activity in vitro than paeonol. This understanding can help to predict the conditions of optimization of poly(butyl-2-cyanoacrylate) nanoparticles formation and to improve paeonol bioavailability and pharmacological properties.

Graphical abstract

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Identification of responsive proteins in Panonychus citri exposed to abamectin by a proteomic approach

Publication date: Available online 20 February 2017
Source:Journal of Proteomics
Author(s): Xiao-Min Shen, Rui Zhong, Wen-Kai Xia, Dong Wei, Tian-Bo Ding, Chong-Yu Liao, Jin-Zhi Niu, Wei Dou, Jin-Jun Wang
Abamectin is a microbial-derived pesticide widely used for control of agricultural pests. However, sustained use of abamectin has led to the development of resistance in some target species. Previous studies on arthropod resistance to abamectin have mainly used traditional biochemical and molecular approaches. To understand the responses of citrus red mite, Panonychus citri, exposed to abamectin, comparative proteomic analysis was conducted using two-dimensional electrophoresis (2-DE). A total of 26 distinct protein spots were present in response to abamectin exposure. Tandem mass spectrometry (MS/MS) identified 16 proteins that were mainly involved in energy metabolism and detoxification. Some remaining proteins were not identifiable, suggesting that they may be novel. The expression levels of transcripts associated with proteins were analyzed by quantitative reverse transcription PCR (qRT-PCR). Furthermore, to validate the proteomic data obtained in the present study, Western-blot experiment was performed and the expression of sHsp and PcE1 proteins were confirmed, respectively.Biological significanceThe citrus red mite has developed resistance to many acaricides, including abamectin. In the current study, we used the proteomic approaches involving 2-DE, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), and MS/MS to document changes in adult P. citri during 24h of abamectin exposure. Abamectin stress induced a total of 16 differentially regulated proteins. The proteomic results were validated in mRNA expression patterns using qRT-PCR. This is the first analysis of differentially expressed proteins in P. citri exposed to abamectin. The results help clarify the physiological mechanisms of P. citri responses to abamectin exposure.

Graphical abstract

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Is a “gut full” of bad bugs driving metabolic disease in shift workers?

Shift workers make up a significant proportion of the total workforce in industrialised countries, with about one in five employees working during night time hours.1 There is strong epidemiological evidence that these workers are at increased risk for developing obesity, type II diabetes, coronary heart disease, stroke and cancer.2 Furthermore, obesity can contribute to worsening of other conditions that are commonly suffered by shift workers such as sleep apnoea. The mechanisms that promote obesity and metabolic disease amongst shift workers are thought to arise from an imposed chronic disruption and misalignment between circadian rhythms, sleep cycles and eating patterns.

http://ift.tt/2mh4ceo

Mexametric and cutometric assessment of the signs of aging of the skin area around the eyes after the use of non-ablative fractional laser, non-ablative radiofrequency and intense pulsed light

Abstract

The assessment of the signs of aging within eyes area in cutometric (skin elasticity) and mexametric (discoloration and severity of erythema) examination after the treatment with: non-ablative fractional laser, non-ablative radiofrequency (RF) and intense light source (IPL). This study included 71 patients, aged 33–63 years (the average age was 45.81) with Fitzpatrick skin type II and III. 24 patients received 5 successive treatment sessions with a 1,410-nm non-ablative fractional laser in two-week intervals, 23 patients received 5 successive treatment sessions with a non-ablative RF in one-week intervals and 24 patients received 5 successive treatment sessions with an IPL in two-week intervals. The treatment was performed for the skin in the eye area. The Cutometer and Mexameter (Courage + Khazaka electronic) reference test was used as an objective method for the assessment of skin properties: elasticity, skin pigmentation and erythema. Measurements of skin elasticity were made in three or four sites within eye area. The results of cutometric measurements for R7 showed the improvement in skin elasticity in case of all treatment methods. The largest statistically significant improvement (p < .0001) was observed in case of laser and RF, during treatment sessions, at sites at upper and lower eyelid. The smallest change in skin elasticity for the laser, RF and IPL – p = .017, p = .003 and p = .001, respectively—was observed in a site within the outer corner of the eye. In all sites of measurements and for all methods, the greatest improvement in skin elasticity was demonstrated between the first and second measurement (after 3rd procedures). The majority of the results of mexametric measurements—MEX (melanin level) and ERYT (the severity of erythema) are statistically insignificant. Fractional, non-ablative laser, non-ablation RF and intense light source can be considered as methods significantly affecting elasticity and to a lesser extent erythema and skin pigmentation around the eyes. Fractional non-ablative laser is a method which, in comparison to other methods, has the greatest impact on skin viscoelasticity. These procedures are well tolerated and are associated with a low risk of side effects.

http://ift.tt/2lBm3PR

The role of nicotinamide in acne treatment

Abstract

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti-inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patient's baseline or performed similarly to another standard-of-care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first-line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.

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Commentary: Prostate cancer screening—A long run for a short slide

Publication date: Available online 20 February 2017
Source:Seminars in Oncology
Author(s): Howard L. Parnes




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Evaluation of RAG1 mutations in an adult with combined immunodeficiency and progressive multifocal leukoencephalopathy

Publication date: Available online 20 February 2017
Source:Clinical Immunology
Author(s): Claudia Schröder, Niklas Baerlecken, Ulrich Pannicke, Thilo Dörk, Torsten Witte, Roland Jacobs, Matthias Stoll, Klaus Schwarz, Bodo Grimbacher, Reinhold E. Schmidt, Faranaz Atschekzei
Here we describe novel mutations in recombination activation gene 1 (RAG1) in a compound heterozygous male patient with combined T and B cell immunodeficiency (CID). Clinical manifestations besides antibody deficiency included airway infections, granulomatosis and autoimmune features. He died at the age of 37 due to PML caused by JC virus infection.By targeted next-generation sequencing we detected post mortem in this patient three mutations in RAG1. One allele harbored two novel mutations (c.1123C>G, p.H375D and c.1430delC, p.F478Sfs*14), namely a missense variant and a frameshift deletion, of which the latter leads to a truncated RAG1 protein. The other allele revealed a previously described missense mutation (c.1420C>T, p.R474C, rs199474678). Functional analysis of the p.R474C variant in an in vitro V(D)J recombination assay exhibited reduced recombination activity compared to a wild-type control. Our findings suggest that mutations in RAG1, specifically the p.R474C variant, can be associated with relatively mild clinical symptoms or delayed occurrence of T cell and B cell deficiencies but may predispose to PML.



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Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis

Publication date: Available online 20 February 2017
Source:Clinical Immunology
Author(s): Lauren M.F. Merlo, Samantha Grabler, James B. DuHadaway, Elizabeth Pigott, Kaylend Manley, George C. Prendergast, Lisa D. Laury-Kleintop, Laura Mandik-Nayak
Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with no known cure. Recently, we identified the immunomodulatory enzyme indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B and T cell responses driving RA. However, therapeutically targeting IDO2 has been challenging given the lack of small molecules that specifically inhibit IDO2 without also affecting the closely related IDO1. In this study, we develop a novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2. Treatment with IDO2-specific mAb alleviated arthritis in two independent preclinical arthritis models, reducing autoreactive T and B cell activation and recapitulating the strong anti-arthritic effect of genetic IDO2 deficiency. Mechanistic investigations identified FcγRIIb as necessary for mAb internalization, allowing targeting of an intracellular antigen traditionally considered inaccessible to mAb therapy. Taken together, our results offer preclinical proof of concept for antibody-mediated targeting of IDO2 as a new therapeutic strategy to treat RA and other autoantibody-mediated diseases.

Graphical abstract

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Clogging development and hydraulic performance of the horizontal subsurface flow stormwater constructed wetlands: a laboratory study

Abstract

The horizontal subsurface constructed wetland (HSSF CW) is a highly effective technique for stormwater treatment. However, progressive clogging in HSSF CW is a widespread operational problem. The aim of this study was to understand the clogging development of HSSF CWs during stormwater treatment and to assess the influence of microorganisms and vegetation on the clogging. Moreover, the hydraulic performance of HSSF CWs in the process of clogging was evaluated in a tracer experiment. The results show that the HSSF CW can be divided into two sections, section I (circa 0–35 cm) and section II (circa 35–110 cm). The clogging is induced primarily by solid entrapment in section I and development of biofilm and vegetation roots in section II, respectively. The influence of vegetation and microorganisms on the clogging appears to differ in sections I and II. The tracer experiment shows that the hydraulic efficiency (λ) and the mean hydraulic retention time (t _mean) increase with the clogging development; although, the short-circuiting region (S) extends slightly. In addition, the presence of vegetation can influence the hydraulic performance of the CWs, and their impact depends on the characteristics of the roots.

http://ift.tt/2lGvUEF

Irisin in goldfish (Carassius auratus): effects of irisin injections on feeding behavior and expression of appetite regulators, uncoupling proteins and lipoprotein lipase, and fasting-induced changes in FNDC5 expression

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Zahndra Diann Butt, Jessica Dalton Hackett, Hélène Volkoff
Irisin is a peptide cleaved from the fibronectin type III domain containing protein 5 (FNDC5) gene that is secreted predominantly by muscle cells but also by other tissues including brain and intestine. In mammals, irisin has been shown to have thermogenic actions via the modulation of uncoupling proteins (UCPs) and to affect feeding and energy homeostasis via actions in brain, adipose tissue, liver, muscle and gastrointestinal tract. To examine the role of irisin on feeding and metabolism in fish, the effects of peripheral (intraperitoneal) injections of irisin on feeding behavior, glucose levels and the mRNA expressions of appetite regulators (cocaine and amphetamine regulated transcript CART, agouti related protein AgRP, orexin), UCPs and lipoprotein lipase LPL and brain factors (brain-derived neurotrophic factor , BDNF and tyrosine hydroxylase TH) were assessed in brain, white muscle and intestine. Irisin injections (100ng/g) induced a decrease in food intake and increases in brain orexin, CART1 and CART2, UCP2, BDNF, muscle UCP2 and intestine LPL mRNA expressions but did not affect blood glucose levels, brain AgRP, TH, UCP1, UCP3 and LPL or muscle UCP1, UCP3 and LPL expressions. A partial goldfish FNDC5 cDNA was isolated and the expressions of FDNC5, UCPs, LPL and BDNF were also compared between fed and fasted fish. Fasting induced decreases FNDC5 mRNA expression in the brain and intestine, but not in muscle. Fasting also induced increases in brain BDNF and LPL expressions and increases in UCP1, UCP2, UCP3 and LPL expressions in muscle. Our result suggest that irisin is an anorexigenic factor in fish and its actions might be in part mediated by appetite-regulating factors such as CART and orexins as well as UCP2 and brain factors such as BDNF.



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Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells. Treatment with DYN 3-14 (10nM) resulted in 35% inhibition of the LPS-induced nuclear translocation of NF-κB/p65. Furthermore, DYN 3-14 modulated both IL-1β and TNF-α release; inhibiting IL-1β and paradoxically augmenting TNF-α release in a concentration-independent manner. A number of opioids have been implicated in the modulation of the toll-like receptor 4 (TLR4), highlighting the complexity of their immunomodulatory effects. To determine whether DYN 3-14 modulates TLR4, HEK-Blue™⁻hTLR4 cells were stimulated with LPS in the presence of DYN 3-14. DYN 3-14 (10μM) inhibited TLR4 activation in a concentration-dependent fashion by suppressing the LPS signals around 300-fold lower than LPS-RS, a potent TLR4 antagonist. These findings indicate that DYN 3-14 is a potential TLR4 antagonist that alters cellular signaling in response to LPS and cytokine release, implicating a role for biotransformed endogenous opioid peptides in immunomodulation.



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Obestatin Improves Oxidative Brain Damage and Memory Dysfunction in Rats Induced with an Epileptic Seizure

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Türkan Koyuncuoğlu, Caner Vızdıklar, Doğan Üren, Hakan Yılmaz, Çağan Yıldırım, Sefa Semih Atal, Dilek Akakın, Elif Kervancıoğlu-Demirci, Meral Yüksel, Berrak Ç. Yeğen
Obestatin was shown to alleviate renal, gastrointestinal and haemorrhage-induced brain injury in rats. In order to investigate the neuroprotective effects of obestatin on seizure-induced oxidative brain injury, an epileptic seizure was induced with a single intraperitoneal (i.p.) dose of pentylenetetrazole (PTZ, 45mg/kg) in male Wistar rats. Thirty minutes before the PTZ injection, rats were treated with either saline or obestatin (1μg/kg, i.p.). Seizure was video-taped and then evaluated by using Racine's scoring (0-5). For the assessment of memory function, passive-avoidance test was performed before seizure induction, which was repeated on the 3rd day of seizure. The rats were decapitated at the 24th or 72nd hour of seizures and brain tissues were obtained for histopathological examination and for measuring levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen radicals and myeloperoxidase (MPO) activity. Obestatin treatment reduced the average seizure score, decreased the occurrence and duration of generalized tonic-clonic seizures, presenting with a shorter latency to their onset. Increased lipid peroxidation and enhanced generation of oxygen-derived radicals detected at the post-seizure 72nd h were suppressed by the consecutive treatments of obestatin, but no changes were observed by the single obestatin treatment in the 24-h seizure group. Neuronal damage and increased GFAP immunoreactivity, observed in the hippocampal areas and cortex of PTZ-induced rats were alleviated in 3-day obestatin-treated PTZ group. PTZ-induced memory dysfunction was significantly improved in obestatin-treated PTZ group as compared to saline-treated rats. The present data indicates that obestatin ameliorated the severity of PTZ-induced seizures, improved memory dysfunction and reduced neuronal damage by limiting oxidative damage.



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Association between circulating angiotensin-converting enzyme 2 and cardiac remodeling in hypertensive patients

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Shichao Li, Zhijun Wang, Xiuhong Yang, Bo Hu, Yuling Huang, Sujing Fan
BackgroundAngiotensin-converting enzyme 2 (ACE2) plays a vital role in the pathogenesis of hypertension-induced cardiac remodeling and exhibits cardioprotective properties in hypertensive animal models. Evidence that ACE2 is an important regulator of hypertensive cardiac remodeling in humans has not been addressed directly yet.MethodsA total of 161 patients with essential hypertension and 47 age- and sex-matched normotensive healthy subjects were consecutively recruited. Serum concentration levels of ACE2 were determined by enzyme-linked immunosorbent assay. Cardiac structural and functional parameters were measured by echocardiography.ResultsSerum ACE2 concentrations were higher in hypertensive patients compared to healthy subjects (170.31 [83.50–707.12] pg/ml in patients versus 59.28 [39.71–81.81] pg/ml in healthy subjects, P<0.001). After adjustment for confounders, including age, sex, body mass index, snoring, smoking, duration of hypertension, comorbidities, medication use, mean arterial pressure and N-terminal pro-brain natriuretic peptide, serum ACE2 concentrations were positively correlated with left atrial diameter, left ventricular end-diastolic diameter and left ventricular mass in hypertensive patients. Moreover, multiple regression analyses adjusting for covariates revealed that serum ACE2 concentrations were also independently associated with left ventricular ejection fraction and late diastolic filling velocities of the mitral inflow.ConclusionsThis study reveals an elevated serum concentration of ACE2 and independent associations between serum ACE2 and echocardiographic parameters in hypertensive patients.



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Editorial board

Publication date: 1 March 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 5





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New insights into highly potent tyrosinase inhibitors based on 3-heteroarylcoumarins: Anti-melanogenesis and antioxidant activities, and computational molecular modeling studies

Publication date: 1 March 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 5
Author(s): Francesca Pintus, Maria J. Matos, Santiago Vilar, George Hripcsak, Carla Varela, Eugenio Uriarte, Lourdes Santana, Fernanda Borges, Rosaria Medda, Amalia Di Petrillo, Benedetta Era, Antonella Fais
Melanogenesis is a physiological pathway for the formation of melanin. Tyrosinase catalyzes the first step of this process and down-regulation of its activity is responsible for the inhibition of melanogenesis. The search for molecules capable of controlling hyperpigmentation is a trend topic in health and cosmetics. A series of heteroarylcoumarins have been synthesized and evaluated. Compounds 4 and 8 exhibited higher tyrosinase inhibitory activities (IC50=0.15 and 0.38μM, respectively), than the reference compound, kojic acid (IC50=17.9μM). Compound 4 acts as competitive, while compound 8 as uncompetitive inhibitor of mushroom tyrosinase. Furthermore, compounds 2 and 8 inhibited tyrosinase activity and melanin production in B16F10 cells. In addition, compounds 2–4 and 8 proved to have an interesting antioxidant profile in both ABTS and DPPH radicals scavenging assays. Docking experiments were carried out in order to study the interactions between these heteroarylcoumarins and mushroom tyrosinase.

Graphical abstract

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Synthesis of bulky-tailed sulfonamides incorporating pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-1(5H)-yl) moieties and evaluation of their carbonic anhydrases I, II, IV and IX inhibitory effects

Publication date: Available online 21 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mohamed Fares, Radwa A. Eladwy, Alessio Nocentini, Soha R. Abd El Hadi, Hazem A. Ghabbour, Ashraf Abdel-Megeed, Wagdy M. Eldehna, Hatem A. Abdel-Aziz, Claudiu T. Supuran
Using celecoxib as lead, two novel series of sulfonamides incorporating the pyridotriazolopyrimidine scaffold have been synthesized and evaluated in vitro as inhibitors against four relevant human (h) carbonic anhydrases (CAs, EC 4.2.1.1), the cytosolic and ubiquitous hCA I and II as well as the transmembrane hCA IV and hCA IX. Most of the reported sulfonamides acted as efficient, low micromolar inhibitors of hCAI, II and IV, whereas they displayed higher efficacy in inhibiting the tumor-associated isoform hCA IX. Many derivates herein reported showed better hCA IX versus hCA II selectivity ratios compared to celecoxib or acetazolamide. Considering isoform IX is a validated target for the diagnosis and treatment of hypoxic tumors, discovery of selective CA IX inhibitors represents a promising step to unveil more effective anticancer therapies.

Graphical abstract

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A PEGylated analog of short-length neuromedin U with potent anorectic and anti-obesity effects

Publication date: Available online 21 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hiroshi Inooka, Kotaro Sakamoto, Tokuyuki Shinohara, Yasushi Masuda, Michiko Terada, Satoshi Kumano, Kotaro Yokoyama, Jiro Noguchi, Naoki Nishizawa, Hidenori Kamiguchi, Hisashi Fujita, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki
Neuromedin U (NMU) is a neuropeptide known to regulate food intake and energy homeostasis that is widely distributed in the gastrointestinal tract, hypothalamus, and pituitary. A short form of NMU, porcine NMU-8 has potent agonist activity for the receptors NMUR1 and NMUR2; however, its short half-life precludes its effective use in vivo. To address this limitation, we designed and synthesized NMU-8 analogs modified by polyethyleneglycol (PEG) with a molecular weight of 30 kDa (PEG30k) via a variety of linkers (i.e., ω-amino- and ω-imino-carboxylic acid linker). Integrated evaluation of NMUR1 and NMUR2 binding affinities in vitro and anorectic activity in mice revealed that the introduction of a linker with a rigid ring group, e.g., 2-(piperazin-1-yl)acetic acid (PipAc), yielded a highly potent anorectic peptide, PEG30k-PipAc-NMU-8 (14), possessing improved receptor binding affinity. Subsequent optimization of the molecular weight of the PEG moiety led to the discovery of a PEG20k conjugate (15), which exhibited significant anti-obesity effect upon once-daily subcutaneous administration in diet-induced obese mice with 10% and 22% body weight loss at doses of 10 and 30 nmol/kg, respectively. In addition, 15 reduced the weights of the liver and adipose tissue in a dose-dependent manner and improved the plasma biochemical parameters, e.g., insulin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and total cholesterol. Thus, our results suggest that 15, which showed potent and long-lasting biological profiles in vivo, represents a candidate peptide for investigating the central and peripheral actions of NMU and its potential for clinical use.

Graphical abstract

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Discovery of Selective ATP-competitive eIF4A3 Inhibitors

Publication date: Available online 20 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Masahiro Ito, Misa Iwatani, Yusuke Kamada, Satoshi Sogabe, Shoichi Nakao, Toshio Tanaka, Tomohiro Kawamoto, Samuel Aparicio, Atsushi Nakanishi, Yasuhiro Imaeda
Eukaryotic initiation factor 4A3 (eIF4A3), an ATP-dependent RNA helicase, is a core component of exon junction complex (EJC). EJC has a variety of roles in RNA metabolism such as translation, surveillance, and localization of spliced RNA. It is worthwhile to identify selective eIF4A3 inhibitors with a view to investigating the functions of eIF4A3 and EJC further to clarify the roles of the ATPase and helicase activities in cells. Our chemical optimization of hit compound 2 culminated in the discovery of ATP-competitive eIF4A3 inhibitor 18 with submicromolar ATPase inhibitory activity and excellent selectivity over other helicases. Hence, compound 18 could be a valuable chemical probe to elucidate the detailed function of eIF4A3 and EJC.

Graphical abstract

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Extraction of the 3D Local Orientation of Myocytes in Human Cardiac Tissue Using X-ray Phase-Contrast Micro-Tomography and Multi-Scale Analysis

Publication date: Available online 20 February 2017
Source:Medical Image Analysis
Author(s): François Varray, Iulia Mirea, Max Langer, Françoise Peyrin, Laurent Fanton, Isabelle E. Magnin
This paper presents a methodology to access the 3D local myocyte arrangements in fresh human post-mortem heart samples. We investigated the cardiac micro-structure at a high and isotropic resolution of 3.5 μm in three dimensions using X-ray phase micro-tomography at the European Synchrotron Radiation Facility. We then processed the reconstructed volumes to extract the 3D local orientation of the myocytes using a multi-scale approach with no segmentation. We created a simplified 3D model of tissue sample made of simulated myocytes with known size and orientations, to evaluate our orientation extraction method. Afterwards, we applied it to 2D histological cuts and to eight 3D left ventricular (LV) cardiac tissue samples. Then, the variation of the helix angles, from the endocardium to the epicardium, was computed at several spatial resolutions ranging from 3.6³ mm³ to 112³ μm³. We measure an increased range of 20°to 30°from the coarsest resolution level to the finest level in the experimental samples. This result is in line with the higher values measured from histology. The displayed tractography demonstrates a rather smooth evolution of the transmural helix angle in six LV samples and a sudden discontinuity of the helix angle in two septum samples. These measurements bring a new vision of the human heart architecture from macro- to micro-scale.

Graphical abstract

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Task FMRI data analysis based on supervised stochastic coordinate coding

Publication date: Available online 20 February 2017
Source:Medical Image Analysis
Author(s): Jinglei Lv, Binbin Lin, Qingyang Li, Wei Zhang, Yu Zhao, Xi Jiang, Lei Guo, Junwei Han, Xintao Hu, Christine Guo, Jieping Ye, Tianming Liu
Task functional magnetic resonance imaging (fMRI) has been widely employed for brain activation detection and brain network analysis. Modeling rich information from spatially-organized collection of fMRI time series is challenging because of the intrinsic complexity. Hypothesis-driven methods, such as the general linear model (GLM), which regress exterior stimulus from voxel-wise functional brain activity, are limited due to overlooking the complexity of brain activities and the diversity of concurrent brain networks. Recently, sparse representation and dictionary learning methods have attracted increasing interests in task fMRI data analysis. The major advantage of this methodology is its promise in reconstructing concurrent brain networks systematically. However, this data-driven strategy is, to some extent, arbitrary and does not sufficiently utilize the prior information of task design and neuroscience knowledge. To bridge this gap, we here propose a novel supervised sparse representation and dictionary learning framework based on stochastic coordinate coding (SCC) algorithm for task fMRI data analysis, in which certain brain networks are learned with known information such as pre-defined temporal patterns and spatial network patterns, and at the same time other networks are learned automatically from data. Our proposed method has been applied to two independent task fMRI datasets, and qualitative and quantitative evaluations have shown that our method provides a new and effective framework for task fMRI data analysis.

Graphical abstract

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Listening to public concerns on vaccinations in order to provide information in a timely manner

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Nobutoshi Nawa, Shigetoyo Kogaki, Keiichi Ozono




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Policy making for vaccine use as a driver of vaccine innovation and development in the developed world

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Katherine Seib, Andrew J. Pollard, Philippe de Wals, Ross M. Andrews, Fangjun Zhou, Richard J. Hatchett, Larry K. Pickering, Walter A. Orenstein
In the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development.



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Editorial Board/Aims and Scope

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10





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Omp16-based vaccine encapsulated by alginate-chitosan microspheres provides significant protection against Haemophilus parasuis in mice

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Xintian Zheng, Xiaoyan Yang, Xiaohua Li, Guo-Hua Qiu, Ailing Dai, Qichun Huang, Cuiqin Huang, Xiaofeng Guo
Haemophilus parasuis (H. parasuis) is the etiological agent of swine Glässer's disease, which leads to significant economic loss in swine industry over the world. Subunit vaccine based on outer membrane protein is one of the promising choices to protect pigs against H. parasuis infection despite low immunity efficiency. In this paper, outer membrane protein 16 (Omp16) of H. parasuis encapsulated by alginate-chitosan microspheres as antigen carriers was explored for the first time in a mouse model. Our results showed that the microspheres with Omp16 induced significant higher H. parasuis-specific antibodies, and higher titers of IL-2, IL-4, and IFN-γ than those by Omp16-FIA in treated mice (p<0.05). Moreover, H. parasuis load in the tissues from liver, spleen, and lung of mice immunized with microspheres containing Omp16 was significantly decreased (p<0.05) than that in the same counterpart tissues of control groups. In addition, 80% mice treated with Omp16 and 70% mice with Omp16-FIA were survived after challenged with H. parasuis virulent strain LY02 (serovar 5). Therefore, Omp16-based microsphere vaccine induces both humoral and cellular immune responses and provides promising protection against H. parasuis infection in mice.



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Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in healthy adults: A phase I/II, observer-blind, randomized, controlled trial

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Anuradha Madan, Murdo Ferguson, Eric Sheldon, Nathan Segall, Laurence Chu, Azhar Toma, Paul Rheault, Damien Friel, Jyoti Soni, Ping Li, Bruce L. Innis, Anne Schuind
BackgroundH7 influenza strains have pandemic potential. AS03-adjuvanted H7N1 A/mallard/Netherlands/12/2000 split-virion vaccine formulations were evaluated as model H7-subtype vaccine and tested after H7N9 emerged in China, and caused severe human disease with high mortality.MethodsIn this phase I/II, observer-blind, randomized trial in US and Canada, 420 healthy adults (21–64years) were randomized to receive 1 of 4 H7N1 vaccine formulations (3.75 or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B), 15μg unadjuvanted H7N1 hemagglutinin, or saline placebo, given as 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays, at day 42 (21days post-dose 2), month 6, and month 12 (HI only) for the per-protocol cohorts (398, 379 and 368 participants, respectively). Safety is reported up to month 12.ResultsBeneficial AS03 adjuvant effect was demonstrated. Committee for Medical Products for Human Use, and Center for Biologics Evaluation and Research (CBER) criteria were met for all adjuvanted formulations at day 42 (H7N1 HI assay); seroprotection (SPR) and seroconversion rates (SCR) were 88.5–94.8%, mean geometric increase (MGI) 19.2–34.9, and geometric mean titers (GMT) 98.3–180.7. Unadjuvanted H7N1 vaccine did not meet CBER criteria. In adjuvanted groups, antibody titers decreased over time; month 12 SPRs and GMTs were low (2.0–18.8% and 8.1–12.2). MN antibodies showed similar kinetics, with titers persisting at higher range than HI at month 6. All adjuvanted groups showed cross-reactivity against H7N9, with HI responses similar to H7N1.The most frequent solicited symptom in adjuvanted groups was injection site pain (71.2–86.7%); grade 3 solicited symptoms were infrequent. Nine participants reported 17 serious adverse events; none were considered causally related to vaccination.ConclusionsAdjuvanted H7N1 vaccine formulations had an acceptable safety profile and induced an antibody response after 2 doses with cross-reactivity to H7N9.ClinicalTrials.gov: NCT01934127



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Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Michaël Bernier, Etienne Croteau, Christian-Alexandre Castellano, Stephen C. Cunnane, Kevin Whittingstall
Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas.



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Predictive modelling using neuroimaging data in the presence of confounds

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Anil Rao, Joao M. Monteiro, Janaina Mourao-Miranda
When training predictive models from neuroimaging data, we typically have available non-imaging variables such as age and gender that affect the imaging data but which we may be uninterested in from a clinical perspective. Such variables are commonly referred to as 'confounds'. In this work, we firstly give a working definition for confound in the context of training predictive models from samples of neuroimaging data. We define a confound as a variable which affects the imaging data and has an association with the target variable in the sample that differs from that in the population-of-interest, i.e., the population over which we intend to apply the estimated predictive model. The focus of this paper is the scenario in which the confound and target variable are independent in the population-of-interest, but the training sample is biased due to a sample association between the target and confound. We then discuss standard approaches for dealing with confounds in predictive modelling such as image adjustment and including the confound as a predictor, before deriving and motivating an Instance Weighting scheme that attempts to account for confounds by focusing model training so that it is optimal for the population-of-interest. We evaluate the standard approaches and Instance Weighting in two regression problems with neuroimaging data in which we train models in the presence of confounding, and predict samples that are representative of the population-of-interest. For comparison, these models are also evaluated when there is no confounding present. In the first experiment we predict the MMSE score using structural MRI from the ADNI database with gender as the confound, while in the second we predict age using structural MRI from the IXI database with acquisition site as the confound. Considered over both datasets we find that none of the methods for dealing with confounding gives more accurate predictions than a baseline model which ignores confounding, although including the confound as a predictor gives models that are less accurate than the baseline model. We do find, however, that different methods appear to focus their predictions on specific subsets of the population-of-interest, and that predictive accuracy is greater when there is no confounding present. We conclude with a discussion comparing the advantages and disadvantages of each approach, and the implications of our evaluation for building predictive models that can be used in clinical practice.



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Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Georg S. Kranz, Rene Seiger, Ulrike Kaufmann, Allan Hummer, Andreas Hahn, Sebastian Ganger, Martin Tik, Christian Windischberger, Siegfried Kasper, Rupert Lanzenberger
Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are – at least in part – responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males.



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Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Aurore Menegaux, Chun Meng, Julia Neitzel, Josef G. Bäuml, Hermann J. Müller, Peter Bartmann, Dieter Wolke, Afra M. Wohlschläger, Kathrin Finke, Christian Sorg
Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults.A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity.The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults.These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery.



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Magnetic resonance fingerprinting based on realistic vasculature in mice

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Philippe Pouliot, Louis Gagnon, Tina Lam, Pramod K. Avti, Chris Bowen, Michèle Desjardins, Ashok K. Kakkar, Eric Thorin, Sava Sakadzic, David A. Boas, Frédéric Lesage
Magnetic resonance fingerprinting (MRF) was recently proposed as a novel strategy for MR data acquisition and analysis. A variant of MRF called vascular MRF (vMRF) followed, that extracted maps of three parameters of physiological importance: cerebral oxygen saturation (SatO2), mean vessel radius and cerebral blood volume (CBV). However, this estimation was based on idealized 2-dimensional simulations of vascular networks using random cylinders and the empirical Bloch equations convolved with a diffusion kernel. Here we focus on studying the vascular MR fingerprint using real mouse angiograms and physiological values as the substrate for the MR simulations. The MR signal is calculated ab initio with a Monte Carlo approximation, by tracking the accumulated phase from a large number of protons diffusing within the angiogram. We first study the identifiability of parameters in simulations, showing that parameters are fully estimable at realistically high signal-to-noise ratios (SNR) when the same angiogram is used for dictionary generation and parameter estimation, but that large biases in the estimates persist when the angiograms are different. Despite these biases, simulations show that differences in parameters remain estimable. We then applied this methodology to data acquired using the GESFIDE sequence with SPIONs injected into 9 young wild type and 9 old atherosclerotic mice. Both the pre injection signal and the ratio of post-to-pre injection signals were modeled, using 5-dimensional dictionaries. The vMRF methodology extracted significant differences in SatO2, mean vessel radius and CBV between the two groups, consistent across brain regions and dictionaries. Further validation work is essential before vMRF can gain wider application.



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Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Rui Cao, Jun Li, Bo Ning, Naidi Sun, Tianxiong Wang, Zhiyi Zuo, Song Hu
A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters—oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO2 is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.



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Macroanatomy and 3D probabilistic atlas of the human insula

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Isabelle Faillenot, Rolf A. Heckemann, Maud Frot, Alexander Hammers
The human insula is implicated in numerous functions. More and more neuroimaging studies focus on this region, however no atlas offers a complete subdivision of the insula in a reference space. The aims of this study were to define a protocol to subdivide insula, to create probability maps in the MNI152 stereotaxic space, and to provide normative reference volume measurements for these subdivisions.Six regions were manually delineated bilaterally on 3D T1 MR images of 30 healthy subjects: the three short gyri, the anterior inferior cortex, and the two long gyri.The volume of the insular grey matter was 7.7 ± 0.9cm³ in native space and 9.9 ± 0.6cm³ in MNI152 space. These volumes expressed as a percentage of the ipsilateral grey matter volume were minimally larger in women (2.7±0.2%) than in men (2.6±0.2%). After spatial normalization, a stereotactic probabilistic atlas of each subregion was produced, as well as a maximum-probability atlas taking into account surrounding structures.Automatically labelling insular subregions via a multi-atlas propagation and label fusion strategy (MAPER) in a leave-one-out experiment showed high spatial overlaps of such automatically defined insular subregions with the manually derived ones (mean Jaccard index 0.65, corresponding to a mean Dice index of 0.79), with an average mean volume error of 2.6%.Probabilistic and maximum probability atlases and the original delineations are available on the web under free academic licences.

Graphical abstract

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Metacognitive ability correlates with hippocampal and prefrontal microstructure

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Micah Allen, James C. Glen, Daniel Müllensiefen, Dietrich Samuel Schwarzkopf, Francesca Fardo, Darya Frank, Martina F. Callaghan, Geraint Rees
The ability to introspectively evaluate our experiences to form accurate metacognitive beliefs, or insight, is an essential component of decision-making. Previous research suggests individuals vary substantially in their level of insight, and that this variation is related to brain volume and function, particularly in the anterior prefrontal cortex (aPFC). However, the neurobiological mechanisms underlying these effects are unclear, as qualitative, macroscopic measures such as brain volume can be related to a variety of microstructural features. Here we leverage a high-resolution (800µm isotropic) multi-parameter mapping technique in 48 healthy individuals to delineate quantitative markers of in vivo histological features underlying metacognitive ability. Specifically, we examined how neuroimaging markers of local grey matter myelination and iron content relate to insight as measured by a signal-theoretic model of subjective confidence. Our results revealed a pattern of microstructural correlates of perceptual metacognition in the aPFC, precuneus, hippocampus, and visual cortices. In particular, we extend previous volumetric findings to show that right aPFC myeloarchitecture positively relates to metacognitive insight. In contrast, decreased myelination in the left hippocampus correlated with better metacognitive insight. These results highlight the ability of quantitative neuroimaging to reveal novel brain-behaviour correlates and may motivate future research on their environmental and developmental underpinnings.



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Heterogeneous fractionation profiles of meta-analytic coactivation networks

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Angela R. Laird, Michael C. Riedel, Mershack Okoe, Radu Jianu, Kimberly L. Ray, Simon B. Eickhoff, Stephen M. Smith, Peter T. Fox, Matthew T. Sutherland
Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d=20–300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how "parent" functional brain systems decompose into constituent "child" sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication.



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Frequency-specific electrophysiologic correlates of resting state fMRI networks

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Carl D. Hacker, Abraham Z. Snyder, Mrinal Pahwa, Maurizio Corbetta, Eric C. Leuthardt
Resting state functional MRI (R-fMRI) studies have shown that slow (<0.1Hz), intrinsic fluctuations of the blood oxygen level dependent (BOLD) signal are temporally correlated within hierarchically organized functional systems known as resting state networks (RSNs) (Doucet et al., 2011). Most broadly, this hierarchy exhibits a dichotomy between two opposed systems (Fox et al., 2005). One system engages with the environment and includes the visual, auditory, and sensorimotor (SMN) networks as well as the dorsal attention network (DAN), which controls spatial attention. The other system includes the default mode network (DMN) and the fronto-parietal control system (FPC), RSNs that instantiate episodic memory and executive control, respectively. Here, we test the hypothesis, based on the spectral specificity of electrophysiologic responses to perceptual vs. memory tasks (Klimesch, 1999; Pfurtscheller and Lopes da Silva, 1999), that these two large-scale neural systems also manifest frequency specificity in the resting state. We measured the spatial correspondence between electrocorticographic (ECoG) band-limited power (BLP) and R-fMRI correlation patterns in awake, resting, human subjects. Our results show that, while gamma BLP correspondence was common throughout the brain, theta (4–8Hz) BLP correspondence was stronger in the DMN and FPC, whereas alpha (8–12Hz) correspondence was stronger in the SMN and DAN. Thus, the human brain, at rest, exhibits frequency specific electrophysiology, respecting both the spectral structure of task responses and the hierarchical organization of RSNs.



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Group B streptococcal carriage, antimicrobial susceptibility, and virulence related genes among pregnant women in Alexandria, Egypt

Publication date: Available online 21 February 2017
Source:Alexandria Journal of Medicine
Author(s): Salama Mohamed Sadaka, Hala Abdelsalam Aly, Marwa Ahmed Meheissen, Yasser Ibrahim Orief, Basma Mohamed Arafa
Background and aimGroup B Streptococcus (GBS) has emerged as a leading cause of illness and death among neonates. The study was conducted to estimate the prevalence of recto-vaginal carriage of GBS among pregnant women at 35–37weeks, gestation, to describe GBS antimicrobial susceptibility profile and to investigate selected virulence genes by PCR.Subjects and methodsTwo-hundred pregnant women at 35–37weeks of gestation attending antenatal clinic at Al-Shatby University Hospital were enrolled in the study. Both vaginal and rectal swabs were collected from each subject. Swabs were inoculated onto CHROMagar™ StrepB and sheep blood agar plates. All GBS isolates were subjected to antimicrobial susceptibility testing using disc diffusion. Disc approximation test was performed to detect erythromycin resistance phenotype (MLSB). GBS virulence genes scpB, bac, bca, and rib were identified by PCR.ResultsAmong the 200 pregnant women, 53 (26.5%) were identified as GBS carriers. All carriers had vaginal colonization (100%), four (7.5%) had combined recto-vaginal colonization. None of the carriers had rectal colonization alone. All isolates (100%) were susceptible to penicillin, ampicillin, ceftriaxone, cefotaxime, cefepime, vancomycin, and linezolid. On the other hand, 43.4%, 28.3%, 22.6%, and 15% of isolates were resistant to levofloxacin, azithromycin, erythromycin, and clindamycin respectively. Out of 12 erythromycin resistant isolates, six isolates had constitutive while two had inducible MLSB resistance. scpB was identified in 100%, rib in 79.2%, and bac in 35.8% of GBS isolates. None of the isolates possessed the bca gene.ConclusionIntroduction of GBS screening in Egyptian pregnant women is recommended. Penicillin or ampicillin is still the antibiotic of choice for intrapartum prophylaxis.



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The developmental relationship between central dopaminergic level and response inhibition from late childhood to young adulthood

Publication date: Available online 20 February 2017
Source:International Journal of Psychophysiology
Author(s): Ting Zhang, Qin Zhang, Cuicui Wang, Antao Chen
Dopamine (DA) is known to modulate response inhibition (RI). In contrast to the abundant adult studies, only few developmental studies have focused on this topic. Moreover, the mechanism underlying the modulation of RI by the DA system from childhood to adulthood remains unclear. We aimed to assess whether the relationship between DA and RI during late childhood and young adulthood is similar. Accordingly, DA function was measured using the spontaneous eye blink rate (EBR), whereas RI ability was tested using the Go/Nogo task. Experiment 1 included 149 adults (age range, 18–25years) who completed the EBR test and the Go/Nogo task; the results showed that higher EBR was associated with lower commission error in the Nogo trials. Experiment 2 included 45 children (age range, 10–12years) and 37 adults (age range, 18–19years) who completed the EBR test and Go/Nogo tasks (similar to experiment 1); in both the child and adult groups, higher EBR was related to better RI ability. As EBR is closely related to central DA function, these findings suggest that DA plays a similar role in the processing of RI in late childhood and young adulthood.



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Renaud Mazeron, 1977-2016

Publication date: Available online 21 February 2017
Source:Brachytherapy





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Immunoprofiling as a predictor of patient’s response to cancer therapy—promises and challenges

Publication date: April 2017
Source:Current Opinion in Immunology, Volume 45
Author(s): Daniel Bethmann, Zipei Feng, Bernard A Fox
Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1. Soon, automated staining methods will improve reproducibility of multiplex staining and allow for CLIA standards so that multiplex staining can be used to make clinical decisions. Ultimately, machine-learning algorithms will help interpret data from tissue images and lead to improved delivery of precision medicine.



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Computed Tomography Angiography in Head and Neck Emergencies

Publication date: Available online 20 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Nikhil Madhuripan, Oliver David Atar, Richard Zheng, Mary Tenenbaum
Computed tomography angiography offers a rapid means of evaluating the vasculature of the head and neck in patients presenting with acute neurological symptoms and blunt trauma to the head and neck. CTA is noninvasive, easy to acquire, and offers excellent detail in identifying site and nature of the lesion. The learning objectives of this review article are to review normal anatomy and variants, recognize CTA appearance of vascular pathologies, describe typical parameters utilized for acquiring the study and recognize common pitfalls.



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Ultrasound Emergencies of the Male Pelvis

Publication date: Available online 20 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Kimberly Weatherspoon, Stanley Polansky, Tara Catanzano
Male pelvic emergencies are uncommon, and symptoms typically include scrotal pain, scrotal enlargement and/or a palpable scrotal mass. Ultrasound is often the first line modality for evaluation of male pelvic emergencies, which may be stratified into vascular, infectious or traumatic causes. Entities like testicular torsion; Fournier′s gangrene and testicular dislocation are surgical emergencies and should not be missed or misdiagnosed, as this may cause a significant delay in urgently necessary treatment. Radiologists need to be familiar with the role of imaging as well as the key characteristic imaging findings of these injuries in order to direct the appropriate management.



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Recognition and Appropriate Use of MRI for Emergent Neuroradiology

Publication date: Available online 20 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Joseph M. Rozell, Shan Li
The use of magnetic resonance imaging (MRI) for the diagnosis of emergent life threatening neurological conditions and what are considered "do not miss" pathologies has dramatically risen over the last ten years due to its increasing importance in the Emergency Department (ED). Although Computed Tomography is likely to remain the more significantly utilized imaging modality due to lower cost and faster speeds, continuing technological advances in MRI have made its use more mainstream. Knowledge of specific clinical signs and symptoms as well as the technical limitations of MRI should help to guide ED clinicians with both the recognition and the appropriate use of emergent MRI.



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Neurologic Emergencies on Computed Tomography of the Head

Publication date: Available online 20 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Jed Hollingsworth, Mae Mae Mirabelli
The purpose of this manuscript is to provide the reader, either a seasoned radiologist, a budding resident, or a curious practitioner, the background necessary to accurately and swiftly interpret a head CT in the emergency setting. At the very least, being able to generate a reasonable differential diagnosis is the aim and will be accomplished by describing not only features of classic neurologic emergencies, but the possible traps to which one may fall prey. Images will be used to illustrate cases and the reader will be instructed when other imaging modalities may be required to clarify diagnoses.



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The Four Quadrants: Acute Pathology in the Abdomen and Current Imaging Guidelines

Publication date: Available online 20 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Bradley Mattson, Kal Dulaimy
With several different imaging options available, it′s not surprising that healthcare providers are unsure which imaging study is most appropriate for evaluating patients who present to the emergency department with abdominal pain. The American College of Radiology currently has appropriateness criteria for patients presenting with right upper, right lower, and left lower quadrant pain and there are different variants for each of these quadrants. Clinicians should be aware of the ACR appropriateness criteria and, whenever possible, should be using the criteria as guide to help them order the most appropriate imaging study.



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Imaging of Female Pelvic Emergencies

Publication date: Available online 20 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Daniel P. Thut, Michael S. Morrow, Christopher C. Moore
Pelvic pain is a common complaint in female patients who present to the Emergency Department. Although encountered frequently, the path to a definitive diagnosis is not always a straightforward one, and imaging offers a valuable tool to aid in this diagnostic challenge. Radiologists must be familiar with the most common etiologies of female pelvic pain in the emergency setting, their imaging characteristics, and the best way to further evaluate challenging clinical presentations. This will allow the radiologist to serve as a valuable asset to the treating physician, aiding in accurate diagnosis and in guiding the course of treatment, all while ensuring the "Image Wisely" principle. A sonographic approach to female patients presenting to the emergency setting with pelvic pain has been presented in this article and some example entities along with their imaging findings have also been reviewed.



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Adenosine A2 receptor activation ameliorates mitochondrial oxidative stress upon reperfusion through the posttranslational modification of NDUFV2 subunit of complex I in the heart

Publication date: Available online 20 February 2017
Source:Free Radical Biology and Medicine
Author(s): Jingman Xu, Xiyun Bian, Yuan Liu, Lan Hong, Tianming Teng, Yuemin Sun, Zhelong Xu
While it is well known that adenosine receptor activation protects the heart from ischemia/reperfusion injury, the precise mitochondrial mechanism responsible for the action remains unknown. This study probed the mitochondrial events associated with the cardioprotective effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine A2 receptor agonist. Isolated rat hearts were subjected to 30min ischemia followed by 10min of reperfusion, whereas H9c2 cells experienced 20min ischemia and 10min reperfusion. NECA prevented mitochondrial structural damage, decreases in respiratory control ratio (RCR), and collapse of mitochondrial membrane potential (ΔΨm). Both the adenosine A2A receptor antagonist SCH58261 and A2B receptor antagonist MRS1706 inhibited the action of NECA. NECA reduced mitochondrial proteins carbonylation, H2O2, and superoxide generation at reperfusion, but did not change superoxide dismutase (SOD) activity. In support, the protective effects of NECA and Peg-SOD on ΔΨm upon reperfusion were additive, implying that NECA's protection is attributable to the reduced superoxide generation but not to the enhancement of the superoxide-scavenging capacity. NECA increased the mitochondrial Src tyrosine kinase activity and suppressed complex I activity at reperfusion in a Src-dependent manner. NECA also reduced mitochondrial superoxide through Src tyrosine kinase. Studies with liquid chromatography-mass spectrometer (LC-MS) identified Tyr118 of the NDUFV2 subunit of complex 1 as a likely site of the tyrosine phosphorylation. Furthermore, the complex I activity of cells transfected with the Y118F mutant was increased, suggesting that this site might be a negative regulator of complex I activity. In support, NECA failed to suppress complex I activity at reperfusion in cells transfected with the Y118F mutant of NDUFV2. In conclusion, NECA prevents mitochondrial oxidative stress by decreasing mitochondrial superoxide generation through inhibition of complex I via the mitochondrial Src tyrosine kinase. Phosphorylation of Tyr¹¹⁸ residue in NDUFV2 subunit may account for the inhibitory effect of NECA on complex I.

Graphical abstract

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Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol

Publication date: Available online 20 February 2017
Source:Free Radical Biology and Medicine
Author(s): Sari Honda, Yuya Fukuyama, Hisashi Nishiwaki, Akiko Masuda, Toshiya Masuda
In this study, the mechanism of the xanthine oxidase (XO) inhibitory activity of pyrogallol, the main inhibitor found in roasted coffee, was investigated. Pyrogallol was unstable and readily converted to purpurogallin in a pH 7.4 solution, a physiological model of human body fluids. The XO inhibitory activity of the produced purpurogallin was higher than that of pyrogallol, as evidenced by comparing their IC50 values (0.2 µmol L⁻¹ for purpurogallin, 1.6 µmol L⁻¹ for pyrogallol). The XO activity of pyrogallol was enhanced by pre-incubation in pH 7.4 solution. Although the initial XO inhibitory activity of 4-methylpyrogallol was weak (IC50 33.3 µmol L⁻¹), its XO inhibitory activity was also enhanced by pre-incubation in the pH 7.4 solution. In contrast, 5-methylpyrogallol, which could not be transformed into corresponding purpurogallin derivatives, did not show XO inhibitory activity before or after incubation in pH 7.4 solution. Molecular docking simulations clarified that purpurogallins have stronger affinities for XO than corresponding pyrogallols. These results revealed that the potent XO inhibitory activity seemingly observed in pyrogallol is actually derived from its chemical conversion, under alkaline conditions, into purpurogallin.

Graphical abstract

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Muscle Response to Complete Peripheral Nerve Injury: Changes of Acetylcholine Receptor and Creatine Kinase Activity over Time

J reconstr Microsurg
DOI: 10.1055/s-0037-1598619

Background This study was designed to assess the changes of acetylcholine receptor (AChR) and creatine kinase (CK) levels, which are important biochemical markers for muscle viability in cases of long-term muscle denervation. Scientists and peripheral nerve surgeons may find these data important regarding maximal range of muscle viability applicable for timing of effective peripheral nerve reconstructive surgery. Methods The study was conducted on 48 rats (96 gastrocnemius muscles), whose right legs were denervated by removing a 10-mm segment of sciatic nerve, while their left legs remained intact. Under general anesthesia, the rats were euthanized at seven points in time, on days 7, 14, 21, 30, 60, 120, and 210. In both legs, AChR was quantified by 125I-α-bungarotoxin, whereas CK activity was measured using a spectrophotometric method. Results CK levels in the denervated limb reached a minimal level of 34% on day 30 in comparison to the intact limb and remained at this level up to 210 days after operation. AChR levels in the denervated limb reached a minimal level of 38% on day 120 in comparison to the intact limb and remained at this level up to 210 days after operation. Conclusion The present study shows that AChR and CK levels in rat denervated muscles remain constant at about third of its intact condition for a period of at least a third of rat's lifetime postinjury.
[...]

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Article in Thieme eJournals:
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Forehead flaps for nasal reconstruction: A single-center experience

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Management of Cancer in the Older Age Person: An Approach to Complex Medical Decisions

The management of cancer in older aged people is becoming a common problem due to the aging of the population. There are many variables determining the complex situation that are interconnected. Some of them can be assessed, such as risk of mortality and risk of treatment complications, but many others are still unknown, such as the course of disease, the host-related factors that influence cancer aggressiveness, and the phenotype heralding risk of permanent treatment-related damage.

This article presents a dynamic and personalized approach to older people with cancer based on our experience on aging, cancer, and their biological interactions. Also, novel treatments and management approaches to older individuals, based on their functional age and their social and emotional needs, are thoughtfully explored here. The Oncologist 2017;22:1–8

Implications for Practice: The goal of this article is to suggest a practical approach to complexity, a clinical situation becoming increasingly common with the aging of the population. Beginning with the analysis of two clinical cases, the authors offer an algorithm for approaching cancer in the older person that involves the assessment of life expectancy without cancer, the risk that cancer might compromise a patient's survival, function, or quality of life, and the potential benefits and risks of the treatments based on a clinical evaluation. The authors then review possible laboratory assessment of functional age and the importance of rapid-learning databases in the study of cancer and age.

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Early Palliative Care Reduces End-of-Life Intensive Care Unit (ICU) Use but Not ICU Course in Patients with Advanced Cancer

Background.

Early palliative care for advanced cancer patients improves quality of life and survival, but less is known about its effect on intensive care unit (ICU) use at the end of life. This analysis assessed the effect of a comprehensive early palliative care program on ICU use and other outcomes among patients with advanced cancer.

Patients and Methods.

A retrospective cohort of patients with advanced cancer enrolled in an early palliative care program (n = 275) was compared with a concurrent control group of patients receiving standard care (n = 195) during the same time period by using multivariable logistic regression analysis. The multidisciplinary outpatient palliative care program used early end-of-life care planning, weekly interdisciplinary meetings to discuss patient status, and patient-reported outcomes assessment integrated within the electronic health record.

Results.

Patients in the control group had statistically significantly higher likelihood of ICU admission at the end of life (odds ratios [ORs]: last 6 months, 3.07; last month, 3.59; terminal admission, 4.69), higher likelihood of death in the hospital (OR, 4.14) or ICU (OR, 5.57), and lower likelihood of hospice enrollment (OR, 0.13). Use of chemotherapy or radiation did not significantly differ between groups, nor did length of ICU stay, code status, ICU procedures (other than cardiopulmonary resuscitation), disposition location, and outcomes after ICU admission.

Conclusion.

Early palliative care significantly reduced ICU use at the end of life but did not change ICU events. This study supports early initiation of palliative care for advanced cancer patients before hospitalizations and intensive care. The Oncologist 2017;22:1–6

Implications for Practice: Palliative care has shown clear benefit in quality of life and survival in advanced cancer patients, but less is known about its effect on intensive care. This retrospective cohort study at a university hospital showed that in the last 6 months of life, palliative care significantly reduced intensive care unit (ICU) and hospital admissions, reduced deaths in the hospital, and increased hospice enrollment. It did not, however, change patients' experiences within the ICU, such as number of procedures, code status, length of stay, or disposition. The findings further support that palliative care exerts its benefit before, rather than during, the ICU setting.

http://ift.tt/2lFHi3r