Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Ετικέτες
Κυριακή 9 Απριλίου 2017
Cleft Palate Repair without Lateral Relaxing Incision
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Free-style Deepithelialized Propeller Flaps: An Ideal Local Flap to Obliterate Wounds with Dead Space
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Characterization of the effect of a new commercial transmission detector on radiotherapy beams
Publication date: Available online 9 April 2017
Source:Practical Radiation Oncology
Author(s): Joey P. Cheung, Angelica Perez-Andujar, Olivier Morin
PurposeTo evaluate the influence of a new commercial transmission detector on radiotherapy beams.Methods and MaterialsA transmission detector designed for online treatment monitoring was characterized on a TrueBeam STx linear accelerator with 6MV, 6FFF, 10MV, and 10FFF beams. Measurements of PDDs, inplane and crossplane off-axis profiles at different depths, transmission factors, and skin dose were acquired with 3x3cm2, 5x5cm2, 10x10cm2, 20x20cm2, and 40x40cm2 field sizes at 100 cm and 80 cm SSD. A CC04 chamber was used for all profile and transmission factor measurements. Skin dose was assessed at 100 cm, 90 cm, and 80 cm SSD using a variety of detectors (Roos and Markus parallel-plate chambers, and OSLD). Skin dose was also assessed for various patient sample plans with OSLDs.ResultsThe PDDs showed small differences between the unperturbed and perturbed beams for 100 cm SSD (≤4 mm dmax difference, <1.2% average profile difference) for all field sizes. At 80 cm SSD, the differences were larger (≤8 mm dmax difference, <3% average profile difference). The differences were larger for the flattened beams and larger field sizes. The off-axis profiles showed similar trends. Field penumbras looked similar with and without the transmission detector. Comparisons in the profile central 80% showed a maximum average (maximum) profile difference between all field sizes of 1.0% (2.6%) and 1.4% (6.3%) for 100 cm and 80 cm SSD, respectively. The average measured skin dose increase at 100 cm (80 cm) SSD for 10x10cm2 field size was <4% (<35%) for all energies. For 40x40cm2 field size, this increased to <31% (≤63%). For the sample patient plans, the average skin dose difference was 0.53% (range−6.6% to 10.4%).ConclusionsThe transmission detector has minimal effect on clinically relevant radiotherapy beams for IMRT and VMAT (field sizes 10x10cm2 and less). For larger field sizes, some perturbations are observable which would need to be assessed for clinical impact.
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Clinical outcomes of helical conformal versus non-conformal palliative radiotherapy for axial skeletal metastases
Publication date: Available online 9 April 2017
Source:Practical Radiation Oncology
Author(s): Kara D. Romano, Daniel M. Trifiletti, Kristine Bauer-Nilsen, Nolan A. Wages, William T. Watkins, Paul W. Read, Timothy N. Showalter
PurposePalliative radiotherapy (RT) for bone metastases has traditionally been delivered with conventional, non-conformal RT (NCRT). Conformal RT (CRT) is potentially more complex and expensive than NCRT, but may reduce normal tissue dose and subsequently toxicity. In this retrospective analysis, we compared CRT versus NCRT to investigate the association between conformality and toxicity.Methods/MaterialsA retrospective analysis of patients receiving palliative RT for axial skeletal bone metastases from 2012-2014 was conducted. Patient and treatment characteristics were obtained including dosimetric variables, acute toxicity, and subjective pain during treatment and in the acute post-treatment period (≤ 60 days after completion). Statistical analyses included t-tests, Chi-square tests, and multivariate logistic regression (MVA).Results179 patients and 254 bone metastases were identified (142 CRT, 112 NCRT). The CRT and NCRT groups were well matched for baseline characteristics (number of fractions, field size, treatment sites, and concurrent chemotherapy). In MVA models, technique (CRT vs. NCRT) was not associated with development of acute toxicity. Regarding toxicity, ECOG performance status and total dose were significantly associated with a higher rate of acute toxicity during radiotherapy (OR 0.649 and 1.129 and p = 0.027 and 0.044, respectively); and only a higher number of vertebral bodies in the treatment field was significantly associated with acute toxicity post-treatment (OR 1.219, p = 0.028). CRT was associated with improvement in bone pain during and post treatment (p = 0.049 and 0.045, respectively).ConclusionOur results demonstrate no difference in acute toxicity following palliative radiotherapy with CRT compared to NCRT for painful bone metastases; however, treatment volume did predict for increased toxicity. Larger studies may further elucidate the value of CRT including the impact of dose escalation for bone metastases and differences in patient reported outcomes between RT techniques.SummaryConformal radiotherapy (CRT) may provide improved sparing of normal tissues compared to non-conformal radiotherapy (NCRT), and thus reduce toxicity for patients receiving palliative radiotherapy for bone metastases. In this retrospective analysis, we observed no difference in acute toxicity between treatment techniques (CRT versus NCRT); however, larger treatment volumes were associated with increased toxicity. CRT was associated with improvement in bone pain control.
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Half knowledge is worse than ignorance....... Imperfect understanding is often more dangerous than ignorance
Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices
As the genetic and phenotypic heterogeneities among cells become more appreciated, there is increasing demand for technologies that facilitate high-throughput and high-efficiency single-cell 'omic' analyses in miniaturized and automated formats. This Review discusses the diverse microfluidic methodologies — with a primary focus on valve-, droplet- and nanowell-based platforms — for characterization of the genomes, epigenomes, transcriptomes and proteomes of single cells, and addresses technical considerations and future opportunities.
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Biomimetic nano cargo carriers
Source:Materials Today
Author(s): David Bradley
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Design principles of the beetle's exoskeleton
Source:Materials Today
Author(s): Laurie Donaldson
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Porous 3D graphene that is stronger than steel
Source:Materials Today
Author(s): Laurie Donaldson
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Metallic organic, no pressure, TED talks
Source:Materials Today
Author(s): David Bradley
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Sensor detects variation in magnetic field strength
Source:Materials Today
Author(s): Laurie Donaldson
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3D biofunctional silk materials
Source:Materials Today
Author(s): David Bradley
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Uncovering friction properties in graphene
Source:Materials Today
Author(s): Laurie Donaldson
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Nitrogen gets friendly
Source:Materials Today
Author(s): David Bradley
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Understanding surface defects in catalysis
Source:Materials Today
Author(s): Laurie Donaldson
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CNT-polyester scaffolds don’t miss a beat
Source:Materials Today
Author(s): Cordelia Sealy
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Record-breaking perovskite solar
Source:Materials Today
Author(s): David Bradley
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Shape memory foam composite fills deep wounds
Source:Materials Today
Author(s): Cordelia Sealy
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Nanoparticles’ magnetic attraction targets biofilms
Source:Materials Today
Author(s): Cordelia Sealy
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The role of vitamin D in the endocrinology controlling calcium homeostasis
Source:Molecular and Cellular Endocrinology
Author(s): James C. Fleet
Vitamin D and its' metabolites are a crucial part of the endocrine system that controls whole body calcium homeostasis. The goal of this hormonal control is to regulate serum calcium levels so that they are maintained within a very narrow range. To achieve this goal, regulatory events occur in coordination at multiple tissues, e.g. the intestine, kidney, bone, and parathyroid gland. Production of the vitamin D endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2 D) is regulated by habitual dietary calcium intake and physiologic states like growth, aging, and the menopause. The molecular actions of 1,25(OH)2 D on calcium regulating target tissues are mediated predominantly by transcription controlled by the vitamin D receptor. The primary role for 1,25(OH)2 D during growth is to increase intestinal calcium absorption so that sufficient calcium is available for bone mineralization. However, vitamin D also has specific actions on kidney and bone.
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Eosin fluorescence: A diagnostic tool for quantification of liver injury
Publication date: Available online 9 April 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Hamid Ali, Safdar Ali, Maryam Mazhar, Amjad Ali, Azra Jahan, Abid Ali
Hepatitis is one of the most common life threatening diseases. The diagnosis is mainly based on biochemical analysis such as liver function test. However, histopathological evaluation of liver serves far better for more accurate final diagnosis. The goal of our study was to evaluate the eosin fluorescence pattern in CCl4-induced liver injury model compared with normal and different treatment groups. For this purpose, liver tissues were stained with H/E and examined under bright field microscope but the fluorescence microscopy of H/E stained slides provided an interesting fluorescence pattern and was quite helpful in identifying different structures. Interesting fluorescence patterns were obtained with FITC, Texas Red and Dual channel filter cubes that were quite helpful in identifying different morphological features of the liver. During the course of hepatic injury, liver cells undergo necrosis, apoptosis and overall cellular microenvironment is altered due to the modification of proteins and other intracellular molecules. Intensified eosin fluorescence was observed around the central vein of injured liver compared to normal indicating enhanced binding of eosin to the more exposed amino acid residues. To conclude, eosin fluorescence pattern varies with the health status of a tissue and can be used further for the diagnosis and quantification of severity of various liver diseases.
Graphical abstract
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Primary pigmented nodular adrenocortical disease: literature review and case report of a 6-year-old boy
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Tumor-specific circulating angiogenic progenitors in breast and renal cell cancer: What prospects?
Source:European Journal of Cancer
Author(s): Caroline Bailleux, Fabrice André, Suzette Delaloge
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Perfluoroalkyl substances with isomer analysis in umbilical cord serum in China
Abstract
Perfluoroalkyl substances (PFASs) are a class of widely used chemicals that have been detected in the environment and general population. However, the isomer patterns in human are poorly characterized. Previous studies observed the isomer-specific maternal-fetal transfer of PFASs in human. In our current study, we first examined the profile of PFASs and isomers, including 17 linear PFASs and 10 branched PFOS/PFOA isomers by using isotopic internal standards in umbilical cord serum samples from Guangzhou, China. We collected a total of 321 of cord blood serum samples from July to October in 2013, and analyzed the PFASs concentration with isomer-specific PFASs analysis method. The results showed that 9 out of 17 PFASs (linear PFASs) were detected (>50% detection rate). Perfluorohexane sulfonate (PFHxS, median 3.87 ng/mL) was the predominant, followed by total PFOS (median 2.99 ng/mL) and total PFOA (median 1.23 ng/mL) in cord serum. In addition, 1m-, iso-, ∑3+4+5m-PFOS and iso-PFOA were the branched PFASs detected in the current study. The proportion of linear PFOS (n-PFOS) was 75.16% of ∑PFOS which was similar to the proportion of electrochemical fluorination that produces ca. 70% linear PFOS and 30% branched. On the contrary, linear PFOA (n-PFOA) accounted for 98.69% ∑PFOA in cord serum samples. Our finding indicates distinct PFASs and PFOS/PFOA isomer profile in cord serum, suggesting there might be a different exposure pathway and metabolism of PFASs.
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Osmopriming with CaCl 2 improves wheat ( Triticum aestivum L.) production under water-limited environments
Abstract
This 2-year field study investigates the potential of seed priming to mitigate losses caused by drought stress at different phenophases of wheat. Wheat seeds were soaked either in distilled water or in aerated solution of CaCl2 (ψs −1.25 MPa) for 18 h to accomplish hydropriming and osmopriming, respectively. The soil moisture was maintained at 90–100% field capacity (well-watered) or 45–50% field capacity at vegetative (vegetative drought) and reproductive (terminal drought) phases. Allometric traits leaf area index, leaf area duration, and crop growth rate were initially more affected by vegetative drought; however, terminal drought was more severe at later stages. Drought at both phenophases, especially terminal drought, impaired the entire yield-related traits of wheat; however, osmopriming compensated the drought-induced losses up to a certain extent. Osmopriming improved the wheat grain yield, economic benefits, and allometric traits under vegetative and terminal drought as well as well-watered conditions. It is recommended that the physiological, biochemical, and genetic mechanisms of osmopriming must be explored to find more valuable insights for improving wheat productivity.
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Resilience potential of an Indian Ocean reef: an assessment through coral recruitment pattern and survivability of juvenile corals to recurrent stress events
Abstract
Coral reefs are degraded by the synergistic action of climate and anthropogenic stressors. Coral cover in the Palk Bay reef at the northern Indian Ocean largely declined in the past decade due to frequent bleaching events, tsunami and increased fishing activities. In this study, we carried out a comparative assessment to assess the differences in the recovery and resilience of three spatially distant reefs viz. Vedhalai, Mandapam and Pamban along Palk Bay affected by moderate, severe and low fishing pressure respectively. The assessment was based on the juvenile coral recruitment pattern and its survivability combined with availability of hard substratum, live coral cover and herbivore reef fish stock. The Vedhalai reef has the highest coral cover (14.6 ± 6.3%), and ≥90% of the live corals in Vedhalai and Mandapam were affected by turf algal overgrowth. The density of herbivore reef fish was low in Vedhalai and Mandapam reefs compared to the Pamban reef with relatively few grazing species. The juvenile coral diversity and density were high in the Pamban reef and low in Vedhalai and Mandapam reefs despite high hard substratum cover. In total, 22 species of juvenile corals of 10 genera were recorded in Palk Bay. Comparison of the species diversity of juvenile corals with adult ones suggested that the Pamban reef is connected with other distant reefs whereas Vedhalai and Mandapam reefs were self-seeded. There was no statistically significant difference in the survivability of juvenile corals between the study sites, and in total, ≥90% of the juvenile corals survived the high sedimentation stress triggered by the northeast monsoon and bleaching stress that occurred recurrently. Our results indicated that the human activities indirectly affected the juvenile coral recruitment by degrading the live coral cover and contributed to the spatial variation in the recovery and resilience of the Palk Bay reef. Low species diversity of the juvenile corals will increase the vulnerability of the Palk Bay reef to species-specific endemic threats.
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Processed milk waste recycling via thermal pretreatment and lactic acid bacteria fermentation
Abstract
Processed milk waste (MW) presents a serious problem within the dairy industries due to its high polluting load. Its chemical oxygen demand (COD) can reach values as high as 80,000 mg O2 L−1. This study proposes to reduce the organic load of those wastes using thermal coagulation and recover residual valuable components via fermentation. Thermal process results showed that the COD removal rates exceeded 40% when samples were treated at temperature above 60 °C to reach 72% at 100 °C. Clarified supernatants resulting from thermal treatment of the samples at the temperatures of 60 (MW60), 80 (MW80), and 100 °C (MW100) were fermented using lactic acid bacteria strains without pH control. Lactic strains recorded important final cell yields (5–7 g L−1). Growth mediums prepared using the thermally treated MW produced 73% of the bacterial biomass recorded with a conventional culture medium. At the end of fermentation, mediums were found exhausted from several valuable components. Industrial scale implementation of the proposed process for the recycling of industrial MWs is described and discussed.
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Effect of nutrients on Chlorella pyrenoidosa for treatment of phenolic effluent of coal gasification plant
Abstract
The ability of Chlorella pyrenoidosa, a freshwater microalga, to degrade phenolic effluent of coal-based producer gas plant under ambient conditions was investigated. C. pyrenoidosa was able to grow in high-strength phenolic effluent. Major contaminant present in the effluent was phenol (C6H5OH). The effluent has 1475.3 ± 68 mg/L of initial total phenolic concentration. The effect of nutrients used for algal cultivation in phenol degradation was analyzed by inoculating four different concentrations, viz.,1, 2, 3, and 4 g of wet biomass/L of raw effluent of C. pyrenoidosa mixed with effluent into two batches (with and without nutrients). C. pyrenoidosa was able to degrade more than 95% of the phenol (C6H5OH) concentration with the algal concentrations of 3 and 4 g/L when supplemented with nutrients. With effluent devoid of nutrients, the average percent reduction in total phenolic compounds was observed to a maximum of 46%. No physical changes in the C. pyrenoidosa were observed during degradation. C. pyrenoidosa was able to consume the organic carbon present in the phenolic compounds as carbon source for its growth despite the inorganic carbon supplemented externally.
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Korean Ministry of Environment’s web-based visual consumer product exposure and risk assessment system (COPER)
Abstract
With support from the Korean Ministry of the Environment (ME), our interdisciplinary research staff developed the COnsumer Product Exposure and Risk assessment system (COPER). This system includes various databases and features that enable the calculation of exposure and determination of risk caused by consumer products use. COPER is divided into three tiers: the integrated database layer (IDL), the domain specific service layer (DSSL), and the exposure and risk assessment layer (ERAL). IDL is organized by the form of the raw data (mostly non-aggregated data) and includes four sub-databases: a toxicity profile, an inventory of Korean consumer products, the weight fractions of chemical substances in the consumer products determined by chemical analysis and national representative exposure factors. DSSL provides web-based information services corresponding to each database within IDL. Finally, ERAL enables risk assessors to perform various exposure and risk assessments, including exposure scenario design via either inhalation or dermal contact by using or organizing each database in an intuitive manner. This paper outlines the overall architecture of the system and highlights some of the unique features of COPER based on visual and dynamic rendering engine for exposure assessment model on web.
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Toxicological assessment of tungsten oxide nanoparticles in rats after acute oral exposure
Abstract
Advances in and the rapid growth of the nanotechnology sector have escalated manufacture of nanoparticles (NPs), resulting in a significant increase in the probability of exposure of humans and wildlife to these materials. Many NPs have been found to exert genotoxicity. Therefore, genotoxicity studies are mandatory to assess the toxicity of NPs as a concern of succumbing to genetic diseases and cancers are universal. Tungsten oxide (WO3) NPs are being explored extensively in various fields. However, the toxicological data of WO3 NPs by oral route in mammals is limited. Hence, the goal of the current investigation was to evaluate the acute toxicity of WO3 NPs and microparticles (MPs) after single oral administration with 100, 500 and 1000 mg/kg body weight doses in female Wistar rats. TEM, dynamic light scattering and laser Doppler velocimetry techniques were used to characterise the particles. The genotoxicity studies were conducted using comet, micronucleus and chromosomal aberration assays. Alterations in biochemical indices and metal distribution in various organs were also evaluated. The mean size of WO3 NPs and MPs by TEM was 53.2 ± 1.91 nm and 5.17 ± 3.18 μm, respectively. The results revealed a significant increase in DNA damage and micronuclei and chromosomal aberrations after exposure to 1000 mg/kg dose of WO3 NPs. Significant alterations in aspartate transaminase, alanine transaminase, reduced glutathione, catalase and malondialdehyde levels in serum and liver were found only at the higher dose of WO3 NPs. Tungsten (W) biodistribution was observed in all the tissues in a dose-, time- and organ-dependent manner. In addition, the maximum concentration of W was found in the liver and the least in the brain was observed. The test substances were found to have a relatively low acute toxicity hazard. The data obtained gives preliminary information on the potential toxicity of WO3 NPs and MPs.
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Changes in sucrose and quinine taste reactivity patterns in infant rat pups after exposure to the other tastant
Source:Appetite, Volume 114
Author(s): A.B. Suárez, M.C. Ifrán, R.M. Pautassi, G.V. Kamenetzky
The taste reactivity test is considered as an objective measure to assess the hedonic impact of tastes. Both the appetitive and aversive pattern of responses are plastic and can change based on previous experience. The present study assessed the repertoire of taste responses elicited by sucrose and quinine in preweanling rats, and described changes in these taste reactivity patterns after exposure to the other tastant. We exposed infant rats (17 days old at the start of training) to sweet (2% sucrose) or bitter (0.01% quinine) tastants during 4, 10-min trials in two different random sequences. The subjects were weighed before and after each trial to provide a measure of percent body weight gained. The following taste reactivity responses were registered: duration of mouthing and paw lick, frequency of chin rub, head shake and flailing of the forelimbs, frequency and duration of face washing, wall climbing and paw tread. The consummatory and affective taste responses changed depending on the order in which the solutions were administered. The order of exposure to the tastants did not affect the levels of sucrose intake. Conversely, rat pups showed more ingestive, and fewer aversive, responses to the sweet tastant when access to the solution followed the intraoral infusion of quinine. Likewise, intraoral delivery of quinine elicited a more aversive taste reactivity pattern when delivered after the access to sucrose than when presented to sucrose-naïve pups. This research contributes to the analysis of taste reactivity responses during the early ontogeny of the rat and highlights the importance of previous experiences on the subsequent assessment of rewards.
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Self-diffusion studies by intra- and inter-molecular spin-lattice relaxometry using field-cycling: Liquids, plastic crystals, porous media, and polymer segments
Publication date: Available online 9 April 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Rainer Kimmich, Nail Fatkullin
Field-cycling NMR relaxometry is a well-established technique for probing molecular dynamics in a frequency range from typically a few kHz up to several tens of MHz. For the interpretation of relaxometry data, it is quite often assumed that the spin-lattice relaxation process is of an intra-molecular nature so that rotational fluctuations dominate. However, dipolar interactions as the main type of couplings between protons and other dipolar species without quadrupole moments can imply appreciable inter-molecular contributions. These fluctuate due to translational displacements and to a lesser degree also by rotational reorientations in the short-range limit. The analysis of the inter-molecular proton spin-lattice relaxation rate thus permits one to evaluate self-diffusion variables such as the diffusion coefficient or the mean square displacement on a time scale from nanoseconds to several hundreds of microseconds. Numerous applications to solvents, plastic liquids and polymers will be reviewed. The technique is of particular interest for polymer dynamics since inter-molecular spin-lattice relaxation diffusometry bridges the time scales of quasi-elastic neutron scattering and field-gradient NMR diffusometry. This is just the range where model-specific intra-coil mechanisms are assumed to occur. They are expected to reveal themselves by characteristic power laws for the time-dependence of the mean-square segment displacement. These can be favorably tested on this basis. Results reported in the literature will be compared with theoretical predictions. On the other hand, there is a second way for translational diffusion phenomena to affect the spin-lattice relaxation dispersion. If rotational diffusion of molecules is restricted, translational diffusion properties can be deduced even from molecular reorientation dynamics detected by intra-molecular spin-lattice relaxation. This sort of scenario will be relevant for adsorbates on surfaces or polymer segments under entanglement and chain connectivity constraints. Under such conditions, reorientations will be correlated with translational displacements leading to the so-called RMTD relaxation process (reorientation mediated by translational displacements). Applications to porous glasses, protein solutions, lipid bilayers, and clays will be discussed. Finally, we will address the intriguing fact that the various time limits of the segment mean-square displacement of polymers in some cases perfectly reproduce predictions of the tube/reptation model whereas the reorientation dynamics suggests strongly deviating power laws.
Graphical abstract
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Unique Rash After Beach Vacation
Publication date: Available online 8 April 2017
Source:The Journal of Emergency Medicine
Author(s): Jennifer Pascual, Chaiya Laoteppitaks
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Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study
Source:Vaccine, Volume 35, Issue 19
Author(s): Aderonke Odutola, Martin O.C. Ota, Martin Antonio, Ezra O. Ogundare, Yauba Saidu, Ebenezer Foster-Nyarko, Patrick K. Owiafe, Fatima Ceesay, Archibald Worwui, Olubukola T. Idoko, Olumuyiwa Owolabi, Abdoulie Bojang, Sheikh Jarju, Isatou Drammeh, Beate Kampmann, Brian M. Greenwood, Mark Alderson, Magali Traskine, Nathalie Devos, Sonia Schoonbroodt, Kristien Swinnen, Vincent Verlant, Kurt Dobbelaere, Dorota Borys
BackgroundConserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants.MethodsIn this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8–10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2–3–4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2–4–9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5–9–12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored.Results1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60–67%) and non-10VT (55–61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI −21.5, 19.5) and 2.1% (−20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (−22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins.ConclusionsIn this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints.Funding: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.
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Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge
Source:Vaccine, Volume 35, Issue 19
Author(s): Sukumar Pal, Alison Favaroni, Delia F. Tifrea, Philipp T. Hanisch, Sören E.T. Luczak, Johannes H. Hegemann, Luis M. de la Maza
ObjectivesTo test vaccines, formulated with novel antigens, to protect mice against Chlamydia infections.MethodsTo determine the ability of polymorphic membrane proteins (Pmps) to induce cross-species protective immune responses, recombinant fragments from all nine C. trachomatis serovar E Pmps were used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 as adjuvants. C. muridarum recombinant MOMP and PBS, formulated with the same adjuvants, were used as positive and negative controls, respectively. Mice were challenged intranasally with 104 inclusion-forming units (IFU) of C. muridarum. Animals were weighed daily and at 10days post-challenge, they were euthanized, their lungs harvested, weighed and the number of chlamydial IFU counted.ResultsFollowing vaccination the nine Pmps elicited immune responses. Based on body weight changes, or number of IFU recovered from lungs, mice vaccinated with Pmp C, G or H were the best protected. For example, over the 10-day period, the negative control group vaccinated with PBS lost significantly more body weight than mice immunized with PmpC or G (P<0.05). C. muridarum MOMP vaccinated mice were better protected against body weight losses than any group immunized with Pmps. Also, the median number of IFU recovered from the lungs of mice vaccinated with PmpC (72×106) or PmpH (61×106) was significantly less than from mice immunized with PBS (620×106; P<0.05). As determined by the number of IFU, all Pmps elicited less protection than C. muridarum MOMP (0.078×106 IFU; P<0.05).ConclusionsThis is the first time PmpC has been shown to elicit cross-species protection against a respiratory challenge. Additional work with Pmps C, G and H is recommended to determine their ability to protect animal models against genital and ocular challenges.
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Investigation of phosphorylated adjuvants co-encapsulated with a model cancer peptide antigen for the treatment of colorectal cancer and liver metastasis
Source:Vaccine, Volume 35, Issue 19
Author(s): Tyler J. Goodwin, Leaf Huang
The lipid calcium phosphate nanoparticle is a versatile platform capable of encapsulating a wide range of phosphorylated molecules from single nucleotides to pDNA. The use of this platform has shown great success as an immunotherapeutic vaccine carrier, capable of delivering co-encapsulated phosphorylated adjuvants and peptides. Three potent vaccine formulations were investigated for anti-cancer efficacy. The phosphorylated adjuvants, CpG, 2′3′cGAMP, and 5′pppdsRNA were co-encapsulated with a model phosphorylated tumor specific peptide antigen (p-AH1-A5). The anti-cancer efficacy of these adjuvants was assessed using an orthotopic colorectal liver metastasis model based on highly aggressive and metastatic CT-26 FL3 cells implanted into the cecum wall. The results clearly indicate that the RIG-1 ligand, 5′pppdsRNA, co-encapsulated with the p-AH1-A5 peptide antigen greatly reduced the growth rate of the primary colon cancer as well as arrested the establishment of liver metastasis in comparison to the other adjuvant formulations and unvaccinated controls. Further evaluation of the immune cell populations within the primary tumor confirms the ability of the 5′pppdsRNA adjuvant to boost the adaptive CD8+ T-cell population, while not inciting increased populations of immune suppressive cell types such as T-regulatory cells or myeloid derived suppressor cells. Furthermore, to our knowledge this is the first study to investigate the anti-cancer efficacy of a specific RIG-1 receptor ligand, 5′pppdsRNA, alongside more established TLR 9 (CpG) and STING (2′3′cGAMP) adjuvants in a cancer vaccine. The 5′pppdsRNA vaccine formulation can be a potent immunotherapy, especially when combined with agents that remodel the immune suppressive microenvironment of the tumor.
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Influenza vaccination responses: Evaluating impact of repeat vaccination among health care workers
Source:Vaccine, Volume 35, Issue 19
Author(s): Vivian K.Y. Leung, Louise A. Carolan, Leon J. Worth, Susan A. Harper, Heidi Peck, Danielle Tilmanis, Karen L. Laurie, Monica A. Slavin, Sheena G. Sullivan
ObjectiveTo compare the antibody response to influenza between health care workers (HCWs) who have received multiple vaccinations (high vaccination group) and those who have received fewer vaccinations (low vaccination group).DesignProspective serosurvey.SettingTertiary referral hospital.ParticipantsHealthcare workers.MethodsHealthcare workers were vaccinated with the 2015 southern hemisphere trivalent influenza vaccine. Influenza antibody titres were measured pre-vaccination, 21–28days post-vaccination and 6months post-vaccination. Antibody titres were measured using the haemagglutination inhibition assay. Levels of seropositivity and estimated geometric mean titres were calculated.ResultsOf the 202 HCWs enrolled, 182 completed the study (143 high vaccination and 39 low vaccination). Both vaccination groups demonstrated increases in post-vaccination geometric mean titres, with greater gains in the low vaccination group. Seropositivity remained high in both high and low vaccination groups post-vaccination. The highest fold rise was observed among HCWs in the low vaccination group against the H3N2 component of the vaccine.ConclusionsBoth high and low vaccination groups in our study demonstrated protective antibody titres post-vaccination. The findings from the current study are suggestive of decreased serological response among highly vaccinated HCWs. More studies with larger sample sizes and a greater number of people in the vaccine-naïve and once-vaccinated groups are required to confirm or refute these findings before making any policy changes.
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Vaccination and blood sampling acceptability during Ramadan fasting month: A cross-sectional study in Conakry, Guinea
Source:Vaccine, Volume 35, Issue 19
Author(s): Nathan Peiffer-Smadja, Ramatou Ouedraogo, Eric D'Ortenzio, Papa Ndiaga Cissé, Zahra Zeggani, Abdoul Habib Beavogui, Sylvain Landry Faye, Frédéric Le Marcis, Yazdan Yazdanpanah, Vinh-Kim Nguyen
IntroductionThere are few data on the acceptability of vaccination or blood sampling during Ramadan fasting month in Muslim countries. This could impact vaccination campaigns, clinical trials or healthcare during Ramadan.MethodsUsing a semi-structured questionnaire, we conducted a cross-sectional study on 201 practising Muslims and 10 religious leaders in Conakry, Guinea in the wake of the recent epidemic Ebola epidemic. Acceptability of vaccination and blood sampling during Ramadan were investigated as well as reasons for refusal.ResultsVaccination was judged acceptable during Ramadan by 46% (93/201, 95% CI 0.40–0.53) of practising Muslims versus 80% (8/10, 95% CI 0.49–0.94) of religious leaders (p=0.11). Blood sampling was judged acceptable during Ramadan by 54% (108/201, 95% CI 0.47–0.60) of practising Muslims versus 80% (8/10, 95% CI 0.49–0.94) of religious leaders (p=0.19). The percentage of participants that judged both blood sampling and vaccination acceptable during Ramadan was 40% (81/201, 95% CI 0.34–0.47) for practising Muslims versus 80% (8/10, 95% CI 0.49–0.94) for religious leaders (p=0.048). The most common reasons for refusal of vaccination or blood sampling were that nothing should enter or leave the body during Ramadan (43%), that adverse events could lead to breaking the fast (32%), that blood should not be seen during Ramadan (9%) and that the Quran explicitly forbids it (9%).DiscussionAlthough most Muslims leaders and scientists consider that injections including immunization and blood sampling should be authorized during Ramadan, many Muslims in our study judged vaccination or blood sampling unacceptable when fasting. Widely available recommendations on healthcare during Ramadan would be useful to inform Muslims.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 35, Issue 19
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Expansion and retention of pulmonary CD4+ T cells after prime boost vaccination correlates with improved longevity and strength of immunity against tularemia
Source:Vaccine, Volume 35, Issue 19
Author(s): Lydia M. Roberts, Tara D. Wehrly, Deborah D. Crane, Catharine M. Bosio
Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent intracellular bacterium. Inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. Ftt infections occur naturally in the U.S. and Ftt was developed as a bioweapon. Thus, there is a need for vaccines that protect against this deadly pathogen. Although a live vaccine strain of Francisella tularensis (LVS) exists, LVS fails to generate long-lived protective immunity against modest challenge doses of Ftt. We recently identified an important role for high avidity CD4+ T cells in short-term protection and hypothesized that expanding this pool of cells would improve overall vaccine efficacy with regard to longevity and challenge dose. In support of our hypothesis, application of a prime/boost vaccination strategy increased the pool of high avidity CD4+ T cells which correlated with improved survival following challenge with either increased doses of virulent Ftt or at late time points after vaccination. In summary, we demonstrate that both epitope selection and vaccination strategies that expand antigen-specific T cells correlate with superior immunity to Ftt as measured by survival.
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Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses
Source:Vaccine, Volume 35, Issue 19
Author(s): Xian Tang, Jia Guo, Lin Cheng, Caijun Sun, Li Liu, Teng Zuo, Hui Wang, Ling Chen, Linqi Zhang, Zhiwei Chen
An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain. Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively. Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity. ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer. Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239. Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
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Plant-made virus-like particle vaccines bearing the hemagglutinin of either seasonal (H1) or avian (H5) influenza have distinct patterns of interaction with human immune cells in vitro
Source:Vaccine, Volume 35, Issue 19
Author(s): Hilary E. Hendin, Stéphane Pillet, Amanda N. Lara, Cheng-Ying Wu, Nathalie Charland, Nathalie Landry, Brian J. Ward
IntroductionThe recent emergence of avian influenza strains has fuelled concern about pandemic preparedness since vaccines targeting these viruses are often poorly immunogenic. Weak antibody responses to vaccines have been seen across multiple platforms including plant-made VLPs. To better understand these differences, we compared the in vitro responses of human immune cells exposed to plant-made virus-like particle (VLP) vaccines targeting H1N1 (H1-VLP) and H5N1 (H5-VLP).MethodsPeripheral blood mononuclear cells (PBMC) from healthy adults were stimulated ex vivo with 2-5µg/mL VLPs bearing the hemagglutinin (HA) of either H1N1 (A/California/7/2009) or H5N1 (A/Indonesia/5/05). VLP-immune cell interactions were characterized by confocal microscopy and flow cytometry 30min after stimulation with dialkylaminostyryl dye-labeled (DiD) VLP. Expression of CD69 and pro-inflammatory cytokines were used to assess innate immune activation 6h after stimulation.ResultsH1- and H5-VLPs rapidly associated with all subsets of human PBMC but exhibited unique binding preferences and frequencies. The H1-VLP bound to 88.7±1.6% of the CD19+ B cells compared to only 21.9±1.8% bound by the H5-VLP. At 6h in culture, CD69 expression on B cells was increased in response to H1-VLP but not H5-VLP (22.79±3.42% vs. 6.15±0.82% respectively: p<0.0001). Both VLPs were rapidly internalized by CD14+ monocytes resulting in the induction of pro-inflammatory cytokines (i.e.: IL-8, IL-1β, TNFα and IL-6). However, a higher concentration of the H5-VLP was required to induce a comparable response and the pattern of cytokine production differed between VLP vaccines.ConclusionsPlant-made VLP vaccines bearing H1 or H5 rapidly elicit immune activation and cytokine production in human PBMC. Differences in the VLP-immune cell interactions suggest that features of the HA proteins themselves, such as receptor specificity, influence innate immune responses. Although not generally considered for inactivated vaccines, the distribution and characteristics of influenza receptor(s) on the immune cells themselves may contribute to both the strength and pattern of the immune response generated.
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Assessment of sex-specific differences in adverse events following immunization reporting in Ontario, 2012–15
Source:Vaccine, Volume 35, Issue 19
Author(s): Tara Harris, Jyotsna Nair, Jill Fediurek, Shelley L. Deeks
We assessed sex-specific trends within passive vaccine safety surveillance in Ontario, Canada. AEFIs reported following vaccines administered between 2012 and 2015 were included. There were 2466 AEFI reports; 66.2% were female. Annualized reporting rates were 5.9 and 3.1 per 100,000 population, for females and males respectively. The female:male reporting rate ratio (RRR) was 1.9. Sex-specific differences by age group were greatest in adults 18–64years (RRR 6.3); whereas there were no differences in children <10years. Vaccine-specific RRRs were highest for vaccines recommended for routine use in adults or high risk populations. All event categories were female-predominant. The highest event-specific RRRs were for oculorespiratory syndrome (5.1), anaesthesia/paraesthesia (4.6) and anaphylaxis (3.0). Serious AEFIs (n=113) were more evenly distributed (57.5% female, RRR 1.3) than non-serious (66.6% female, RRR 1.9). AEFI reporting among females was consistently elevated within the passive surveillance system in Ontario. Further study of the relationship between sex/gender and AEFI reporting is needed.
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Identification and characterization of enhancer agonist human cytotoxic T-cell epitopes of the human papillomavirus type 16 (HPV16) E6/E7
Publication date: 2 May 2017
Source:Vaccine, Volume 35, Issue 19
Author(s): Kwong Y. Tsang, Massimo Fantini, Romaine I. Fernando, Claudia Palena, Justin M. David, James W. Hodge, Elizabeth S. Gabitzsch, Frank R. Jones, Jeffrey Schlom
Human papillomavirus (HPV) is associated with the etiology of cervical carcinoma, head and neck squamous cell carcinoma, and several other cancer types. Vaccines directed against HPV virus-like particles and coat proteins have been extremely successful in the prevention of cervical cancer through the activation of host HPV-specific antibody responses; however, HPV-associated cancers remain a major public health problem. The development of a therapeutic vaccine will require the generation of T-cell responses directed against early HPV proteins (E6/E7) expressed in HPV-infected tumor cells. Clinical studies using various vaccine platforms have demonstrated that both HPV-specific human T cells can be generated and patient benefit can be achieved. However, no HPV therapeutic vaccine has been approved by the Food and Drug Administration to date. One method of enhancing the potential efficacy of a therapeutic vaccine is the generation of agonist epitopes. We report the first description of enhancer cytotoxic T lymphocyte agonist epitopes for HPV E6 and E7. While the in silico algorithm revealed six epitopes with potentially improved binding to human leukocyte antigen–A2 allele (HLA-A2)–Class I, 5/6 demonstrated enhanced binding to HLA-Class I in cell-based assays and only 3/6 had a greater ability to activate HPV-specific T cells which could lyse tumor cells expressing native HPV, compared to their native epitope counterparts. These agonist epitopes have potential for use in a range of HPV therapeutic vaccine platforms and for use in HPV-specific adoptive T- or natural killer–cell platforms.
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Corrigendum to “Preclinical studies on new proteins as carrier for glycoconjugate vaccines” [Vaccine 34 (2016) 4235–4242]
Source:Vaccine, Volume 35, Issue 19
Author(s): M. Tontini, M.R. Romano, D. Proietti, E. Balducci, F. Micoli, C. Balocchi, L. Santini, V. Masignani, F. Berti, P. Costantino
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Profiling of selenium absorption and accumulation in healthy subjects after prolonged l -selenomethionine supplementation
Abstract
Purpose
Autoimmune thyroiditis and its complications for the reproductive system are a growing problem. Selenium is a common ingredient in numerous food supplements recommended for thyroiditis and pregnancy. A fast, simple method to measure serum selenium concentration will improve knowledge of its pharmacokinetics and toxicity.
Aim
To validate a useful method to measure serum selenium concentration and to study selenium absorption and accumulation in a prospective interventional study of prolonged treatment.
Methods
Thirty healthy volunteers received a single dose of l-selenomethionine one tablet (83 mcg) (Phase 1), a single dose of two tablets (Phase 2), and two tablets daily for 14 days (Phase 3). Total selenium and selenium time profiles were generated by serial sampling (T0, T3, T6, T12, and T24 hours after ingestion—Phases 1 and 2; and T0 and T24 hours—Phase 3). Selenium concentration was investigated by open-vessel acid digestion of small serum volumes followed by hydride generation atomic fluorescence spectroscopy analysis.
Results
There was a significant increase in serum selenium concentration (mcg/L) in all treatment phases. Significantly increased levels were reached at T3 in Phase 1 (baseline: 76.5 ± 2.47; T3: 82.8 ± 3.28) and at T6 in Phase 2 (83.8 ± 3.46). They remained significantly increased at T12 in Phase 1 and T24 in Phase 2 (79.03 ± 2.69). There was significant selenium accumulation after prolonged intake (14 days) (102.13 ± 5.61).
Conclusions
Prolonged selenomethionine administration increases circulating blood selenium concentration and hydride generation atomic fluorescence spectroscopy enables its accurate quantification.
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Neural Noise Hypothesis of Developmental Dyslexia
Publication date: Available online 8 April 2017
Source:Trends in Cognitive Sciences
Author(s): Roeland Hancock, Kenneth R. Pugh, Fumiko Hoeft
Developmental dyslexia (decoding-based reading disorder; RD) is a complex trait with multifactorial origins at the genetic, neural, and cognitive levels. There is evidence that low-level sensory-processing deficits precede and underlie phonological problems, which are one of the best-documented aspects of RD. RD is also associated with impairments in integrating visual symbols with their corresponding speech sounds. Although causal relationships between sensory processing, print–speech integration, and fluent reading, and their neural bases are debated, these processes all require precise timing mechanisms across distributed brain networks. Neural excitability and neural noise are fundamental to these timing mechanisms. Here, we propose that neural noise stemming from increased neural excitability in cortical networks implicated in reading is one key distal contributor to RD.
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Cognitive Behavior Therapy to Treat Sleep Disturbance and Fatigue Following Traumatic Brain Injury: A Pilot Randomized Controlled Trial
Publication date: Available online 8 April 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Sylvia Nguyen, Adam McKay, Dana Wong, S.M. Rajaratnam, Gershon Spitz, Gavin Williams, Darren Mansfield, Jennie L. Ponsford
ObjectiveTo evaluate the efficacy of adapted cognitive behavioral therapy (CBT) for sleep disturbance and fatigue in individuals with traumatic brain injury (TBI).DesignParallel two-group randomized controlled trial.SettingOutpatient therapy in the Melbourne metropolitan area.ParticipantsTwenty-four adults with history of TBI and clinically significant sleep and/or fatigue complaints were randomly allocated to an eight-session adapted CBT intervention or a treatment as usual (TAU) condition.Main Outcome MeasuresThe primary outcome was the Pittsburgh Sleep Quality Index (PSQI) post-treatment and at two month follow-up. Secondary measures included Insomnia Severity Scale, Fatigue Severity Scale, Brief Fatigue Inventory, Epworth Sleepiness Scale and Hospital Anxiety and Depression Scale.ResultsAt follow-up, CBT recipients reported better sleep quality than those receiving TAU (PSQI mean difference 4.85, 95%CI: 2.56-7.14). Daily fatigue levels were significantly reduced in the CBT group (BFI difference 1.54, 95%CI: 0.66-2.42). Secondary improvements were significant for depression. Large within-group effect sizes were evident across measures (Hedges g=1.14-1.93) with maintenance of gains two months after therapy cessation.ConclusionsAdapted CBT produced greater and sustained improvements in sleep, daily fatigue levels and depression compared to TAU. These pilot findings suggest that CBT is a promising treatment for sleep disturbance and fatigue after TBI.
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Comparative effectiveness of non-operative treatments for chronic calcific tendinitis of the shoulder: A systematic review and network meta-analysis of randomized-controlled trials
Publication date: Available online 8 April 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yi-Cheng Wu, Wen-Chung Tsai, Yu-Kung Tu, Tung-Yang Yu
ObjectiveTo investigate the effectiveness of various non-operative treatments for chronic calcific tendinitis of the shoulder. A systematic review and network meta-analysis of randomized trials was performed to evaluate changes in pain reduction, functional improvements in patients with calcific tendinitis, and the ratio of complete resolution of calcific deposition.Data SourcesStudies were comprehensively searched, without language restrictions on PubMed, Embase, Cochrane Controlled Trials Register, the Cochrane and other databases. The reference lists of articles and reviews were cross-checked for possible studies.Study SelectionRandomized controlled trials from before August 2016 were included. Study selection was conducted by two reviewers independently.Data ExtractionThe quality of studies was assessed and data extracted by two independent reviewers. Disagreements were settled by consulting a third reviewer to reach a consensus.Data SynthesisFourteen studies with 1105 participants were included in the network meta-analysis that used a random-effect model to investigate the mean difference of pooled effect sizes of the visual analog scale, Constant-Murley score, and the ratio of complete resolution of calcific deposition on native radiographs.ConclusionsThe present network meta-analysis demonstrates that ultrasound-guided needling (UGN), radial extracorporeal shockwave (RSW), and high-energy focused extracorporeal shockwave therapy (H-FSW) alleviate pain and achieve complete resolution of calcium deposition. Compared with low-energy focused extracorporeal shockwave (L-FSW), transcutaneous electrical nerve stimulation (TENS), and ultrasound therapy, H-FSW is the best therapy for providing functional recovery. Physicians should consider UGN, RSW, and H-FSW as alternative effective therapies for chronic calcific tendinitis of the shoulder when initial conservative treatment fails.
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Reducing barriers to Patient Reported Outcome Measures for people with cognitive impairments
Publication date: Available online 8 April 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jessica M. Kramer, Ariel Schwartz
The field of rehabilitation has increasingly called for the use of patient reported outcome measures (PROMs) in research and practice. Given that many rehabilitation clients present with conditions associated with cognitive impairments, it is imperative to reduce barriers to PROM use for this population. The purpose of this paper is develop a comprehensive understanding of cognitive accessibility that can prospectively inform the design of PROMs. We put forth the following definition of cognitive accessibility for PROMs: Cognitive accessibility is present when assessment design anticipates respondent variability in cognitive abilities and, to the greatest extent possible, reduces cognitive demands and/or supports cognitive processes to enable respondents with a range of cognitive abilities to interpret and respond to assessment items as intended. Our operationalization of cognitive accessibility in measurement in the field of rehabilitation is informed by two assumptions: 1) cognitive accessibility results from an interaction between the individual's capacities and the demands of the assessment and assessment context, and 2) individuals with cognitive impairments have the right to be involved in decisions about their lives, including healthcare decisions. This paper proposes three design features that can be optimized for cognitive accessibility: content, layout, and administration procedures. We end with a discussion of next steps that the field of rehabilitation measurement can undertake to advance our understanding of cognitive accessibility.
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Evaluating which dose-function metrics are most critical for functional-guided radiotherapy with CT ventilation imaging
Publication date: Available online 8 April 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Austin M. Faught, Tokihiro Yamamoto, Richard Castillo, Edward Castillo, Jingjing Zhang, Moyed Miften, Yevgeniy Vinogradskiy
Purpose4DCT-ventilation imaging is increasingly being used to calculate lung ventilation and implement functional-guided radiotherapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation. The purpose of our study was to evaluate which dose-function metrics best predict for radiation pneumonitis (RP).Methods and MaterialsSeventy lung cancer patients with 4DCT imaging and pneumonitis grading were used. Pre-treatment 4DCTs of each patient were used to calculate ventilation images. We evaluated 3 types of dose function metrics that combined that patient's 4DCT-ventilation image and treatment planning dose distribution: 1) structure-based approaches 2) image-based approaches using the dose-function histogram (DFH) and 3) non-linear weighting schemes. Log-likelihood methods were used to generate normal tissue complication probability (NTCP) models predicting grade 3+ pneumonitis for all dose-function schemes. The area under the curve (AUC) was used to assess the predictive power of the models. All techniques were compared to NTCP models based on traditional, total lung dose metrics.ResultsThe most predictive models were structure-based approaches that focused on the volume of functional lung receiving ≥20Gy (AUC=0.70). Probability of grade 3+ RP of 20% and 10% correspond to V20Gy to the functional sub-volumes of 26.8% and 9.3%, respectively. Imaging-based analysis with the DFH and non-linear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when evaluating the percentage of functionality receiving ≥20Gy. All dose-function metrics outperformed the traditional dose metrics (mean lung dose, AUC=0.55).ConclusionA full range of dose-function metrics and functional thresholds were examined. The calculated AUC values for the most predictive functional models occupied a narrow range (0.66-0.70) and all demonstrated notable improvements over AUC from traditional lung dose metrics (0.55). Identifying the combinations most predictive of grade 3+ RP provides valuable data to inform the functional-guided radiotherapy process.
Teaser
We performed a retrospective analysis of 70 lung cancer patients with 4DCT images to assess which dose-function metrics are most predictive of clinical radiation pneumonitis and should be used in functional-guided radiotherapy. Normal tissue complication probability models were developed based on standard lung dose metrics and four additional functional schemes that considered lung function as determined from 4DCT ventilation imaging. Results provide valuable data in the guidance of prospective clinical trials in functional-guided radiotherapy.http://ift.tt/2nuj8Lb
The interconnection of mental fatigue and aging: An EEG study
Publication date: Available online 8 April 2017
Source:International Journal of Psychophysiology
Author(s): Stefan Arnau, Tina Möckel, Gerhard Rinkenauer, Edmund Wascher
Mental fatigue, a state of reduced alertness and decreased overall performance due to prolonged cognitive activity, is a major cause for a large number of accidents in traffic and industry. Against the background of an aging workforce, the investigation of the interconnection of mental fatigue and aging is of great practical relevance. In the present study, a group of younger and a group of older adults performed a cognitive task for 3h. The experimental design also comprised breaks with various durations. Beside behavioral data, the spectral properties of the ongoing EEG with respect to time on task and breaks were analyzed. No differences between the age groups were found in behavior, but electrophysiological measures provide some evidence that older adults in our study were differentially affected by time on task. In the later course of the experiment modulations in frontal theta power became larger for older, compared to younger adults. This may indicate strain due to task demands, eventually resulting from the deployment of compensatory processes. Occipital alpha, which has been linked to internally oriented brain states, saturates faster in younger adults. It thus maybe, that especially the younger participants' performance deteriorated due to the monotonous nature of the task itself. Both mechanisms, an increased consumption of cognitive resources in older adults and a decrease of motivation in younger adults, could mask differences in performance decrements between the age groups due to mental fatigue.
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Psychophysiological correlates of the misinformation effect
Publication date: Available online 8 April 2017
Source:International Journal of Psychophysiology
Author(s): Katja Volz, Rainer Leonhart, Rudolf Stark, Dieter Vaitl, Wolfgang Ambach
The misinformation effect refers to memory impairment that arises after exposure to misleading information (Loftus, 2005, p. 361). The present study focuses on the peripheral psychophysiology of false memories induced in a misleading information paradigm. On the basis of Sokolov's orienting reflex and studies concerning the Concealed Information Test (CIT, Lykken, 1959), the main hypothesis assumes differences between true and false memories in terms of the accompanying autonomic measures. It also is assumed that a cued recall of original information preceding the recollection phase reduces misinformation effects. Seventy-five participants watched a video that included nine randomized details. After a ten-minute retention phase, the subjects read a narrative text. Six out of the nine details were replaced by misleading details. Following this, the participants completed a cued recall task for three of the original items. In a subsequent CIT with truthful answering electrodermal responses, phasic heart rate, respiration, and response behavior were measured. Finally, the level of confidence and source monitoring were assessed. The misinformation effect was replicated with newly developed materials in three recollection tasks. Cued recall had no influence on the misinformation effect. Autonomic measures did not differ between true and false memories in the CIT. Electrodermal responses reflected the subjective importance the participants attributed to details in the source monitoring task. Therefore, electrodermal responses are interpreted as a correlate of subjective remembering in a misinformation paradigm.
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Enhanced Hydrogen Evolution Reactions on Nanostructured Cu2ZnSnS4 (CZTS) Electrocatalyst
Publication date: 1 August 2017
Source:Applied Surface Science, Volume 412
Author(s): Renuka V. Digraskar, Balaji B. Mulik, Pravin S. Walke, Anil V. Ghule, Bhaskar R. Sathe
A novel and facile one-step sonochemical method is used to synthesize Cu2ZnSnS4 (CZTS) nanoparticles (2.6±0.4nm) as cathode electrocatalyst for hydrogen evolution reactions. The detailed morphology, crystal and surface structure, and composition of the CZTS nanostructures were characterized by high resolution transmission electron microscopy (HR-TEM), Selected area electron diffraction (SAED), X-ray diffraction, Raman spectroscopy, FTIR analysis, Brunauer−Emmett−Teller (BET) surface area measurements, Electron dispersive analysis, X-ray photoelectron spectroscopy respectively. Electrocatalytic abilities of the nanoparticles toward Hydrogen Evolution Reactions (HER) were verified through cyclic voltammograms (CV) and Linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS), and Tafel polarization measurements. It reveals enhanced activity at lower onset potential 300mV v/s RHE, achieved at exceptionally high current density −130mA/cm2, which is higher than the existing non-nobel metal based cathodes. Further result exhibits Tafel slope of 85mV/dec, exchange current density of 882mA/cm2, excellent stability (>500 cycles) and lower charge transfer resistance. This sonochemically fabricated CZTSs nanoparticles are leading to significantly reduce cell cost and simplification of preparation process over existing high efficiency Pt and other nobel metal-free cathode electrocatalyst.
Graphical abstract
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Advancements in the development of TiO2 photoanodes and its fabrication methods for dye sensitized solar cell (DSSC) applications. A review
Publication date: September 2017
Source:Renewable and Sustainable Energy Reviews, Volume 77
Author(s): Muhammad Shakeel Ahmad, A.K. Pandey, Nasrudin Abd Rahim
Dye sensitized solar cells (DSSCs) are widely studied for the safe and reliable energy supply. Due to its low fabrication cost, eco-friendly production and competitive efficiency, this is the promising technology. The components of DSSC which combine to form a photo conversion device are the conducting substrate, dye, photoanode, catalyst and electrolyte. Each component has its own importance but among them photoanode is probability the main component which determines the energy conversion efficiency. Various photoanode materials have been trialled to date. Among them Zn and TiO2 are widely recognized, researched and investigated. In this review attempt will be made to examine the strategies to improve the efficiency of TiO2 photoanode. This review is dedicated to the TiO2 photoanode, its properties, issues related to TiO2 photoanode, various improvement approaches, fabrication methods successfully trialled so far followed by market potential of the DSSC technology, conclusion and recommendations.
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Ab initio thermodynamic study on two-dimensional atomic nucleation on ZnO polar surfaces
Publication date: 1 August 2017
Source:Applied Surface Science, Volume 412
Author(s): Rui Zhu, Qing Zhao, Jun Xu, Banggui Liu, Yamin Leprince-Wang, Dapeng Yu
Structures of the two-dimensional atomic nuclei on ZnO (0001)-Zn and (0001¯)-O polar surfaces were studied by first principles density functional theory. The polarity-dependent nucleation dynamics was investigated by simulating two-dimensional (2D) nuclei consisting of 1-8 ZnO monomers on both polar surfaces. According to total energy calculations, average binding energy per ZnO monomer of the surface nuclei was analyzed to investigate if the nucleation and growth will proceed reasonably in physics. We found nucleation on (0001)-Zn surface was easier than that on (0001¯)-O surface. By using atomistic thermodynamics analysis, we calculated the Gibbs free energy of formation of these nuclei and made a comparison between the two polar surfaces. On (0001)-Zn surface, the critical Gibbs free energy of formation is much lower than that on (0001¯)-O surface under the same supersaturation, which leads to a much larger ZnO growth rate and rougher morphology, in accordance with experimental results. In addition, energetic analysis of nucleation at real thermodynamic conditions was achieved by introducing the temperature- and pressure-dependent chemical potentials of ZnO precursors.
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Reduction removal of hexavalent chromium by zinc-substituted magnetite coupled with aqueous Fe(II) at neutral pH value
Publication date: 15 August 2017
Source:Journal of Colloid and Interface Science, Volume 500
Author(s): Jinhua Zhang, Caihua Zhang, Gaoling Wei, Ying Li, Xiaoliang Liang, Wei Chu, Hongping He, Deyin Huang, Jianxi Zhu, Runliang Zhu
In this study, Cr(VI) removal by Zn-substituted magnetite coupled with aqueous Fe(II) through adsorption and reduction was investigated. A series of Zn-substituted magnetites (Fe3−xZnxO4, x=0, 0.25, 0.49, 0.74 and 0.99) were synthesized by a coprecipitation method, followed by systematic characterization, e.g., X-ray diffraction (XRD), thermogravimetry (TG), specific surface area and surface acid/base titration. The characterization results show that all samples had a spinel structure without an obvious alternation by Zn substitution. The BET surface area and surface site density gradually increased with Zn substitution. During Cr removal under neutral pH value, Cr(VI) was first adsorbed on the magnetite surface and then reduced to Cr(III) by Fe3−xZnxO4 and adsorbed Fe(II); finally, it was immobilized on the Fe3−xZnxO4 surface, which was verified via X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge spectroscopy (XANES) analyses and desorption experiment. With the increase in the Zn content in magnetite, the Cr removal efficiency initially decreased; then, it improved, which was ascribed to the decreasing Cr(VI) reduction and increasing Cr(VI) adsorption. This variation in activity by Zn substitution was discussed in terms of the reaction mechanism as well as the cationic microstructure and surface properties of Fe3−xZnxO4.
Graphical abstract
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Longitudinal Multiple Sclerosis Lesion Segmentation Data Resource
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Aaron Carass, Snehashis Roy, Amod Jog, Jennifer L. Cuzzocreo, Elizabeth Magrath, Adrian Gherman, Julia Button, James Nguyen, Pierre-Louis Bazin, Peter A. Calabresi, Ciprian M. Crainiceanu, Lotta M. Ellingsen, Daniel S. Reich, Jerry L. Prince, Dzung L. Pham
The data presented in this article is related to the research article entitled "Lon- gitudinal multiple sclerosis lesion segmentation: Resource and challenge" [1]. In conjunction with the 2015 International Symposium on Biomedical Imaging, we organized a longitudinal multiple sclerosis (MS) lesion segmentation challenge pro- viding training and test data to registered participants. The training data consists of five subjects with a mean of 4.4 (± 0.55) time-points, and test data of fourteen subjects with a mean of 4.4 (± 0.67) time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. The training data including multi-modal scans and manually delineated lesion masks is available for download11 The data and evaluation website is: http://ift.tt/2k6vIu7. In addition, the testing data is also being made available in conjunction with a website for evaluating the automated analysis of the testing data.
http://ift.tt/2pht4nL
Use of Google street view for urban land use classification in Brooklyn, New York City
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Weixing Zhang, Weidong Li, Chuanrong Zhang, Dean M. Hanink, Xiaojiang Li, Wenjie Wang
Google Street View (GSV) was used for urban land use classification, together with airborne light detection and ranging (LiDAR) data and high resolution orthoimagery, by a parcel-based method. In this data article, we present the input raw GSV images, intermediate products of GSV images, and final urban land use classification data that are related to our research article "Parcel-based urban land use classification in megacity using airborne LiDAR, high resolution orthoimagery, and Google Street View" (Zhang et al., 2017) [1]. More detail about other used data and our findings can be found in Zhang et al. (2017) [1].
http://ift.tt/2phtvhL
Data supporting possible implication of APOBEC2 in self-renewal functions of myogenic stem satellite cells: Toward understanding the negative regulation of myoblast differentiation
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Hideaki Ohtsubo, Yusuke Sato, Takahiro Suzuki, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi
This article provides in vitro phenotypical data to show that APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, may implicate in self-renewal functions of myogenic stem satellite cells, namely in the re-establishment of quiescent status after activation and proliferation of myoblasts in single-myofiber culture.
http://ift.tt/2omvfJj
Data for discriminating dead/live bacteria in homogenous cell suspensions and the effect of insoluble substrates on turbidimetric measurements
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Kwabena O. Duedu, Christopher E. French
Estimation of bacterial growth by rapid traditional methods such as spectrophometric measurements at 600nm (OD600) is not applicable for cultures containing insoluble particles in the growth media. Colony counts are the only suitable alternative but these are laborious and not high-throughput. The data presented in this article is related to the research article entitled "Two-colour fluorescence fluorimetric analysis for direct quantification of bacteria and its application in monitoring bacterial growth in cellulose degradation systems" (K.O. Duedu and C.E. French, 2017) [1]. This data article presents original primary data describing the discrimination of dead/live bacteria in homogenous cell suspensions and how the presence of insoluble substrates affect the turbidity of the suspensions.
http://ift.tt/2phDV0K
Dataset of Effect of Wogonin, a natural flavonoid, on the viability and activation of NF-κB and MAPKs in IL-1β-stimulated human OA chondrocytes
Publication date: Available online 9 April 2017
Source:Data in Brief
Author(s): Nazir M. Khan, Abdul Haseeb, Mohammad Y. Ansari, Pratap Devarapalli, Sara Hyanie, Tariq M. Haqqi
This article contains data related to the article "Wogonin, a plant derived small molecule exerts potent anti-inflammatory and chondroprotective effects through activation of ROS/ERK/Nrf2 signaling pathways in human OA chondrocytes" (Khan NM et al. 2017) [1]. The data are related to effects of Wogonin on the viability and IL-1β-stimulated activation of NF-κB and ERK1/2, JNK1/2 and p38 MAPKs in human OA chondrocytes. Gene expression data representing the chondrogenic phenotype and the efficiency of Nrf2 knockdown in monolayer culture of human OA chondrocytes were shown. Moreover, mass spectrometric calibration curve of Wogonin used to quantify the intracellular uptake were also presented. The data are presented in the form of figures and significance of these has been given in the research article [1].
http://ift.tt/2of8mqT
Data on soil PH of Barddhaman district, India
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Sumanta Bid
PH (Puissance de Hydrogen) is an essential ingredient of soil that effects on fertility and productivity of dirt. Barddhaman district is a part of Lower Gangetic Plain fully covered by alluvial soil and popularly known as 'rice bowl of West Bengal' owing to its lofty production. This data article provides a block level data on soil PH that is essential for further investigation of the relationship among soil ph, plant growth, plant health and productivity. This data is valuable in the field of soil geography and soil science. Soil PH data is more relevant in the ground of plant biology, agricultural geography and agricultural science. It helps to explain the acidic and alkaline nature of alluvial soil. The data consist of 195 samples (n = 195) taken from the entire district. Samples have been collected from March, 2014 to March, 2015 and experimented in the laboratory. Theoretically PH value is limited within 0 to 14. Experiment result exemplifies the highest value 8.5 found in Khandaghosh block whereas lowest value is 4.5 and the samples which result in lowest value are gathered from 4 different blocks like Manteswar, Burdwan - II, Barabani and Salanpur.
http://ift.tt/2phfgtB
Data for TROTS – The Radiotherapy Optimisation Test Set
Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Sebastiaan Breedveld, Ben Heijmen
The Radiotherapy Optimisation Test Set (TROTS) is an extensive set of problems originating from radiotherapy (radiation therapy) treatment planning. This dataset is created for 2 purposes: (1) to supply a large-scale dense dataset to measure performance and quality of mathematical solvers, and (2) to supply a dataset to investigate the multi-criteria optimisation and decision-making nature of the radiotherapy problem. The dataset contains 120 problems (patients), divided over 6 different treatment protocols/tumour types. Each problem contains numerical data, a configuration for the optimisation problem, and data required to visualise and interpret the results. The data is stored as HDF5 compatible Matlab files, and includes scripts to work with the dataset.
http://ift.tt/2oeSSD8
Data on multiple body parameters, microclimatic variables, and subjective assessment of thermal sensation monitored in outdoor environment
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Katerina Pantavou, Anastasios Mavrakis, Georgios K. Nikolopoulos
This article describes two sets of data on multiple body parameters of five participants, on microclimatic variables, and on self-reported assessment of thermal responses, all monitored in the same outdoor urban environment. Data were collected during three seasons, summer, autumn and winter 2010–2011, in the city of Athens, Greece. Part of these data, collected during the summer period, is related to the research article entitled "Case study of skin temperature and thermal perception in a hot outdoor environment." [1].
http://ift.tt/2phedd2
Data on Overlapping Brain Disorders and Emerging Drug Targets in Human Dopamine Receptors Interactions Network
Publication date: Available online 8 April 2017
Source:Data in Brief
Author(s): Avijit Podder, N. Latha
Intercommunication of Dopamine Receptors (DRs) with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled "Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network" (Podder et al., 2014), we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.
http://ift.tt/2of9KcX
Data for transcriptomic and proteomic analyses of leaves from Clematis terniflora DC. under binary stress
Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Bingxian Yang, Qijie Guan, Jingkui Tian, Setsuko Komatsu
High level of UV-B irradiation followed by dark treatment accumulates secondary metabolites in Clematis terniflora DC. To investigate the response mechanism under high level of UV-B irradiation followed by dark treatment, transcriptomic and proteomic analyses were performed in leaves of Clematis terniflora DC. The experimental design for the transcriptomic and proteomic analyses in leaves of C. terniflora under stresses was organized into a picture. For transcriptomics, mRNA-sequencing technology was used. Genes identified in leaves of C. terniflora at starting point, high level of UV-B irradiation, and high level of UV-B irradiation followed by dark treatment were listed; genes with different expression levels at starting point, high level of UV-B irradiation, and high level of UV-B irradiation followed by dark treatment were also presented in this DiB article. For proteomics, a gel-free/label-free proteomic technique was used. Proteins with different abundances in leaves at starting point, high level of UV-B irradiation, and high level of UV-B irradiation followed by dark treatment were presented in this DiB article. In order to monitor the expression levels of genes under the stress, quantitative reverse transcription polymerase chain reaction was performed. The primer sequences of genes selected for quantitative reverse transcription polymerase chain reaction was presented in this DiB article.
http://ift.tt/2phkiGi
Common marmoset (Callithrix jacchus) as a primate model for behavioral neuroscience studies
Source:Journal of Neuroscience Methods
Author(s): Noeline W. Prins, Eric Pohlmeyer, Shubham Debnath, Ramanamurthy Mylavarapu, Shijia Geng, Justin C. Sanchez, Daniel Rothen, Abhishek Prasad
BackgroundThe common marmoset (Callithrix jacchus) has been proposed as a suitable bridge between rodents and larger primates. They have been used in several types of research including auditory, vocal, visual, pharmacological and genetics studies. However, marmosets have not been used as much for behavioral studies.New methodHere we present data from training 12 adult marmosets for behavioral neuroscience studies. We discuss the husbandry, food preferences, handling, acclimation to laboratory environments and neurosurgical techniques. In this paper, we also present a custom built "scoop" and a monkey chair suitable for training of these animals.ResultsThe animals were trained for three tasks: 4 target center-out reaching task, reaching tasks that involved following robot actions, and touch screen task. All animals learned the center-out reaching task within 1-2 weeks whereas learning reaching tasks following robot actions task took several months of behavioral training where the monkeys learned to associate robot actions with food rewards.Comparison to existing methodWe propose the marmoset as a novel model for behavioral neuroscience research as an alternate for larger primate models. This is due to the ease of handling, quick reproduction, available neuroanatomy, sensorimotor system similar to larger primates and humans, and a lissencephalic brain that can enable implantation of microelectrode arrays relatively easier at various cortical locations compared to larger primates.ConclusionAll animals were able to learn behavioral tasks well and we present the marmosets as an alternate model for simple behavioral neuroscience tasks.
http://ift.tt/2oViR0O
Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair.
Publication date: Available online 8 April 2017
Source:Journal of Neuroscience Methods
Author(s): Jonathan P.C. Hasselmann, Hawra Karim, Anna J. Khalaj, Subir Ghosh, Seema K. Tiwari-Woodruff
BackgroundWhile many groups use experimental autoimmune encephalomyelitis (EAE) as a model to uncover therapeutic targets and understand the pathology underlying multiple sclerosis (MS), EAE protocol variability introduces discrepancies in central nervous system (CNS) pathogenesis and clinical disease, limiting the comparability between studies and slowing much-needed translational research.Optimized methodHere we describe a detailed, reliable protocol for chronic EAE induction in C57BL/6 mice utilizing two injections of myelin oligodendrocyte glycoprotein (35-55) peptide mixed with Complete Freund's Adjuvant and paired with pertussis toxin.ResultsThe active MOG35-55 EAE protocol presented here induces ascending paralysis in 80-100% of induced mice. We observe: (1) consistent T cell immune activation, (2) robust CNS infiltration by peripheral immune cells, and (3) perivascular demyelinating lesions concurrent with axon damage in the spinal cord and various brain regions, including the optic nerve, cortex, hippocampus, internal capsules, and the cerebellum.Comparison with existing method(s)Lack of detailed protocols, combined with variability between laboratories, make EAE results difficult to compare and hinder the use of this model for therapeutic development. We provide the most detailed active MOG35-55-EAE protocol to date. With this protocol, we observe high disease incidence and a consistent, reliable disease course. The resulting pathology is MS-like and includes optic neuritis, perivascular mononuclear infiltration, CNS axon demyelination, and axon damage in both infiltrating lesions and otherwise normal-appearing white matter.ConclusionsBy providing a detailed active MOG35-55-EAE protocol that yields consistent and robust pathology, we aim to foster comparability between pre-clinical studies and facilitate the discovery of MS therapeutics.
http://ift.tt/2oVr4lT
In-vitro effect of Human Cathelicidin Antimicrobial Peptide LL-37 on Dengue Virus type 2
Source:Peptides
Author(s): K. Alagarasu, P.S. Patil, P. Shil, M. Seervi, M.B. Kakade, H. Tillu, A. Salunke
Human Cathelicidin antimicrobial peptide LL-37 is known to have antiviral activity against many viruses. In the present study, we investigated the in-vitro effect of LL-37 on dengue virus type 2 (DENV-2) infection and replication in Vero E6 cells. To study the effect of pretreatment of virus or cells with LL-37, the virus was pretreated with different concentrations of LL-37 (2.5μM to 15μM) or scrambled (Scr) LL-37(5μM to 15μM) and used for infection or the cells were first treated with LL-37 and infected. To study the effect of LL-37 post infection (PI), the cells were infected first followed by addition of LL-37 to the culture medium 24hrs after infection. In all conditions, after the incubation, the culture supernatant was assessed for viral RNA copy number by real time RT-PCR, infectious virus particles by focus forming unit assay (FFU) and non structural protein 1 (NS1) antigen levels by ELISA. Percentage of infection was assessed using immunoflourescence assay (IFA). The results revealed that pretreatment of virus with 10–15μM LL-37 significantly reduced its infectivity as compared to virus control (P<0.0001). Moreover, pretreatment of virus with 10–15μM LL-37 significantly reduced the levels of viral genomic RNA and NS1 antigen (P<0.0001). Treatment: of virus with 10–15μM LL-37 resulted in two to three log reduction of mean log10 FFU/ml as compared to virus control (P<0.0001). Treatment: of the virus with scrambled LL-37 had no effect on percentage of infection and viral load as compared to virus control cultures (P>0.05). Pretreatment of cells before infection or addition of LL-37 to the culture 24h PI had no effect on viral load. Molecular docking studies revealed possible binding of LL-37 to both the units of DENV envelope (E) protein dimer. Together, the in-vitro experiments and in-silico analyses suggest that LL-37 inhibits DENV-2 at the stage of entry into the cells by binding to the E protein. The results might have implications for prophylaxis against DENV infections and need further in-vivo studies.
http://ift.tt/2phoJ3P
PEGylated neuromedin U-8 shows long-lasting anorectic activity and anti-obesity effect in mice by peripheral administration
Publication date: Available online 8 April 2017
Source:Peptides
Author(s): Yasushi Masuda, Satoshi Kumano, Jiro Noguchi, Kotaro Sakamoto, Hiroshi Inooka, Tetsuya Ohtaki
Neuromedin U (NMU) is a neuropeptide found in the brain and gastrointestinal tract. The NMU system has been shown to regulate energy homeostasis by both a central and a peripheral mechanism. Peripheral administration of human NMU-25 was recently shown to inhibit food intake in mice. We examined the possibility that other NMU-related peptides exert an anorectic activity by intraperitoneal (i.p.) administration. We found that rat NMU-23 and its structurally-related peptide rat neuromedin S (NMS) significantly reduced food intake in lean mice, whereas NMU-8, an active fragment of the octapeptide sequence conserved in porcine, human and mouse NMU, had no effect. When rat NMU-23, NMU-8, and rat NMS were covalently conjugated to polyethylene glycol (PEG) (PEGylation) at the N-terminus of these peptides, PEGylated NMU-8 showed the most long-lasting and robust anorectic activity. The exploration of the linker between NMU-8 and PEG using hetero-bifunctional chemical cross-linkers led to an identification of PEGylated NMU-8 analogs with higher affinity for NMU receptors and with more potent anorectic activity in lean mice. The PEGylated NMU-8 showed potent and robust anorectic activity and anti-obesity effect in diet-induced obesity (DIO) mice by once-daily subcutaneous (s.c.) administration. These results suggest that PEGylated NMU-8 has the therapeutic potential for treatment of obesity.
Graphical abstract
http://ift.tt/2ph5AyU
GATA4 regulates osteoblastic differentiation and bone remodeling via p38-mediated signaling
Abstract
Osteoblasts play a major role in bone remodeling and are regulated by transcription factors. GATA4, a zinc finger transcription factor from the GATA family, has an unclear role in osteoblast differentiation. In this study, the role of GATA4 in osteoblast differentiation was studied both in vitro and in vivo by GATA4 knockdown. GATA4 expression increased during osteoblast differentiation. GATA4 knockdown in osteoblast precursor cells reduced alkaline phosphatase activity and decreased the formation of calcified nodule in an osteogenic-induced cell culture system. In vivo, micro-CT showed that local injection of lentivirus-delivered GATA4 shRNA caused reduced new bone formation during tooth movement. Histological analyses such as total collagen and Goldner's trichrome staining confirmed these results. In vivo immunohistochemical analysis showed reduced expression of osterix (OSX), osteopontin (OPN), and osteocalcin (OCN) in the shGATA4 group (P < 0.05). Consistently, both western blotting and quantitative reverse-transcription PCR proved that expression of osteogenesis-related genes, including OSX, OPN, and OCN, was significantly repressed in the shGATA4 group in vitro (P < 0.01). For further analysis of the pathways involved in this process, we examined the MAPK signaling pathway, and found knockdown of GATA4, downregulated p38 signaling pathways (P < 0.01). Collectively, these results imply GATA4 is a regulator of osteoblastic differentiation via the p38 signaling pathways.
http://ift.tt/2ph3Ci7
Thyroid High-Impact Articles
FREE ACCESS through April 21, 2017.
Read now:
Latest Impact Factor: 3.784
The Official Journal of: American Thyroid Association
American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
Bryan R. Haugen, Anna M. Sawka, Erik K. Alexander, Keith C. Bible, Patrizio Caturegli, Gerard M. Doherty, Susan J. Mandel, John C. Morris, Aziza Nassar, Furio Pacini, Martin Schlumberger, Kathryn Schuff, Steven I. Sherman, Hilary Somerset, Julie Ann Sosa, David L. Steward, Leonard Wartofsky, Michelle D. Williams
Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy
Mitsuru Ito, Akira Miyauchi, Mako Hisakado, Waka Yoshioka, Akane Ide, Takumi Kudo, Eijun Nishihara, Minoru Kihara, Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Shuji Fukata, Mitsushige Nishikawa, Hirotoshi Nakamura, Nobuyuki Amino
Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Accounts for More Than Half of "Carcinomas" Harboring RAS Mutations
Vera A. Paulson, Priyanka Shivdasani, Trevor E. Angell, Edmund S. Cibas, Jeffrey F. Krane, Neal I. Lindeman, Erik K. Alexander, Justine A. Barletta
Outcome of Large Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
Bin Xu, Giovanni Tallini, Theresa Scognamiglio, Benjamin R. Roman, R. Michael Tuttle, Ronald A. Ghossein
A Novel Gel Pad Laryngeal Ultrasound for Vocal Cord Evaluation
Jung-Woo Woo, Seo Ki Kim, Inhye Park, Jun Ho Choe, Jung-Han Kim, Jee Soo Kim
The post Thyroid High-Impact Articles appeared first on American Thyroid Association.
http://ift.tt/2oVkjAk
ADM guidance—Ceramics: guidance to the use of fractography in failure analysis of brittle materials
Source:Dental Materials
Author(s): Susanne S. Scherrer, Ulrich Lohbauer, Alvaro Della Bona, Alessandro Vichi, Michael J. Tholey, J. Robert Kelly, Richard van Noort, Paulo Francisco Cesar
ObjectivesTo provide background information and guidance as to how to use fractography accurately, a powerful tool for failure analysis of dental ceramic structures.MethodsAn extended palette of qualitative and quantitative fractography is provided, both for in vivo and in vitro fracture surface analyses. As visual support, this guidance document will provide micrographs of typical critical ceramic processing flaws, differentiating between pre- versus post sintering cracks, grinding damage related failures and occlusal contact wear origins and of failures due to surface degradation.ResultsThe documentation emphasizes good labeling of crack features, precise indication of the direction of crack propagation (dcp), identification of the fracture origin, the use of fractographic photomontage of critical flaws or flaw labeling on strength data graphics. A compilation of recommendations for specific applications of fractography in Dentistry is also provided.SignificanceThis guidance document will contribute to a more accurate use of fractography and help researchers to better identify, describe and understand the causes of failure, for both clinical and laboratory-scale situations. If adequately performed at a large scale, fractography will assist in optimizing the methods of processing and designing of restorative materials and components. Clinical failures may be better understood and consequently reduced by sending out the correct message regarding the fracture origin in clinical trials.
http://ift.tt/2oe4F3e
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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