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Παρασκευή 20 Ιανουαρίου 2017

Editorial overview: Developmental neuroscience 2017

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Publication date: Available online 20 January 2017
Source:Current Opinion in Neurobiology
Author(s): Paola Arlotta, Pierre Vanderhaeghen




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Anti-Fibrotic Effects of Chronic Treatment with the Selective FXR Agonist Obeticholic Acid in the Bleomycin-Induced Rat Model of Pulmonary Fibrosis

Publication date: Available online 20 January 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Paolo Comeglio, Sandra Filippi, Erica Sarchielli, Annamaria Morelli, Ilaria Cellai, Francesca Corcetto, Chiara Corno, Elena Maneschi, Alessandro Pini, Luciano Adorini, Gabriella Barbara Vannelli, Mario Maggi, Linda Vignozzi
Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated. Lung function was assessed by measuring airway resistance to inflation.In the acute phase (7 days), bleomycin promoted an initial thickening and fibrosis of the lung interstitium, with upregulation of genes related to epithelial proliferation, tissue remodeling and hypoxia. At 28 days, an evident increase in the deposition of collagen in the lungs was observed. This excessive deposition was accompanied by an upregulation of transcripts related to the extracellular matrix (TGFβ1, SNAI1 and SNAI2), indicating lung fibrosis. Administration of OCA protected against bleomycin-induced lung damage by suppressing molecular mechanisms related to epithelial-to-mesenchymal transition (EMT), inflammation and collagen deposition, with a dose-dependent reduction of proinflammatory cytokines such as IL-1β and IL-6, as well as TGF-β1 and SNAI1 expression. Pirfenidone, a recently approved treatment for idiopathic pulmonary fibrosis (IPF), significantly counteracted bleomycin-induced pro-fibrotic genes expression, but did not exert significant effects on IL-1β and IL-6. OCA treatment in bleomycin-challenged rats also improved pulmonary function, by effectively normalizing airway resistance to inflation and lung stiffness in vivo. Results with OCA were similar, or even superior, to those obtained with pirfenidone.In conclusion, our results suggest an important protective effect of OCA against bleomycin-induced lung fibrosis by blunting critical mediators in the pathogenesis of IPF.



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Individual Placement and Support in Spinal Cord Injury: A Longitudinal Observational Study of Employment Outcomes

Publication date: Available online 20 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Lisa Ottomanelli, Lance L. Goetz, Scott D. Barnett, Eni Njoh, Thomas M. Dixon, Sally Ann Holmes, James LePage, Doug Ota, Sunil Sabharwal, Kevin T. White
ObjectiveTo determine the effects of a 24-month program of Individual Placement and Support (IPS) supported employment (SE) on employment outcomes for veterans with spinal cord injury (SCI).DesignLongitudinal, observational multi-site study of a single arm, non-randomized cohort.SettingSCI centers in the Veterans Health Administration (VHA) (n=7).ParticipantsVeterans with SCI (n=213) enrolled during an episode of either inpatient hospital care (24.4%) or outpatient care (75.6%). More than half the sample (59.2%) had a history of traumatic brain injury (TBI).Intervention(s)IPS SE for 24 months.Main Outcome Measure(s)Competitive employment (CE).ResultsOver the 24-month period, 92 of the entire sample of 213 IPS participants obtained competitive jobs for an overall employment rate of 43.2%. For the subsample of participants without TBI enrolled as outpatients (n=69), 36 obtained competitive jobs for an overall employment rate of 52.2%. Overall, employed participants averaged 38.2 ± 29.7 weeks of employment, with an average time to first employment of 348.3 ± 220.0 days. Nearly 25% of 1st jobs occurred within 4 to 6 months of beginning the program. Similar employment characteristics were observed in the subsample without TBI histories enrolled as outpatients.Conclusion(s): Almost half of the veterans with SCI participating in the 24-month IPS program as part of their ongoing SCI care achieved CE, consistent with their expressed preferences at the start of the study. Among a sub-sample of veterans without any TBI history enrolled as outpatients, employment rates exceeded 50%. Time to first employment was highly variable, but quite long in many instances. These findings support offering continued IPS services as part of ongoing SCI care to achieve positive employment outcomes.



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Longitudinal Investigation of Rehospitalization Patterns in Spinal Cord and Traumatic Brain Injury among Medicare Beneficiaries

Publication date: Available online 20 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Christopher R. Pretz, James E. Graham, Addie Middleton, Amol M. Karmarkar, Kenneth J. Ottenbacher
ObjectiveTo model 12-month rehospitalization risk among Medicare beneficiaries receiving inpatient rehabilitation for SCI or TBI and to create two (SCI- and TBI-specific) interactive tools enabling users to generate monthly projected probabilities for rehospitalization based on an individual patient's clinical profile at discharge from inpatient rehabilitation.DesignSecondary data analysis.SettingMore than 1,100 inpatient rehabilitation facilities across the US.ParticipantsMedicare beneficiaries receiving inpatient rehabilitation for SCI or TBI.Main Outcome MeasureMonthly rehospitalization (yes/no) based on Medicare claims.ResultsResults are summarized through computer-generated interactive tools, which plot individual level trajectories of rehospitalization probabilities over time. Factors associated with the probability of rehospitalization over time are also provided, with different combinations of these factors generating different individual level trajectories. Four case studies are presented to demonstrate the variability in individual risk trajectories. Monthly rehospitalization probabilities for the individual high-risk TBI and SCI cases declined from 33-15% and 41-18%, respectively, over time, whereas the probabilities for the individual low-risk cases were much lower and stable over time: 5-2% and 6-2%, respectively.ConclusionRehospitalization is an undesirable and multifaceted health outcome. Classifying patients into meaningful risk strata at different stages of their recovery is a positive step forward in anticipating and managing their unique healthcare needs over time.



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Complications of Spinal Cord Injury Over the First Year After Discharge from Inpatient Rehabilitation

Publication date: Available online 20 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Michael D. Stillman, Jason Barber, Steve Burns, Steve Williams, Jeanne M. Hoffman
ObjectivesTo describe the prevalence and cumulative incidence (CI) of secondary complications of spinal cord injury (SCI) in the first year after discharge from inpatient rehabilitation (IR). To evaluate potential associations between risk of complications and socio-demographic and injury-specific factors.DesignSecondary analysis of data collected for a single-site, single-blind, randomized controlled trial comparing telephone follow up to usual care.SettingTwo inpatient rehabilitation units comprising the Northwest Regional SCI System in Seattle, Washington.ParticipantsAdults ages 18 or over (n=169) within one year of discharge from IR following SCI.InterventionsNot applicable.Main Outcome MeasuresSelf-report of 10 secondary complications of SCI.ResultsParticipants experienced a mean of 4.7 complications over 12 months. The most frequently reported complications were urinary tract infection (UTI), autonomic dysreflexia (AD), and pressure ulcers with CIs of 62%, 43%, and 41%, respectively. Bone and soft tissue injuries (CI 35%) and bowel problems including "impaction or severe constipation" (CI 33%) were also common. Cumulative incidences of AD, decubitus ulcers, UTI, and problems with bladder were greater in participants with higher level and more complete injuries, and some recurrent complications were common. Age at injury and impairment level significantly affected rates of complications, and subjects developed an average of 2.33 distinct complications during the study period.ConclusionsPeople with SCI are at high-risk for a number of secondary complications over the first year after discharge from IR. While these data offer some insight into who with SCI is at highest risk for first time and recurrent complications, further study is needed to refine this understanding and to develop effective educational and prevention strategies.



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Predatory Open Access in Rehabilitation

Publication date: Available online 20 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Andrea Manca, Gianluca Martinez, Lucia Cugusi, Daniele Dragone, Giuseppe Mercuro, Franca Deriu
Increasingly scholars and researchers are being solicited by predatory "open access" journals seeking manuscript submissions and abusing the author-pays model by charging authors with publishing fees without any or proper peer review. Such questionable editorial practices are threatening the reputation and credibility of scholarly publishing. To date no investigation has been conducted on this phenomenon in the field of rehabilitation. The present study attempts to identify specific predatory journals operating in this field, to quantify the phenomenon and its geographical distribution. Beall's list has been used to this end which, although not perfect, is a comprehensive and up-to-date report of predatory publishers. Of the 1,113 publishers on the list, 59 journals were identified, for a total of 5,610 published articles. The median number of articles published by each journal was 21 and the median amount of the article processing charges was 499 USD. Only 1 out of 59 journals was included in the Directory of Open Access Journals while 7 (12%) were indexed by PubMed. Most of the publishers were based in India (36%) followed by the USA (25%) and Pakistan (5%) and 25% were without a verifiable address.The data indicate that the threat of predatory publishing in rehabilitation is real. Physiatrists, physiotherapists, researchers and academics operating in this field are advised to use the tools available so as to recognize predatory practices before considering publishing in open-access journals.



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Total Synthesis and Cytotoxicity of Leucetta Alkaloids

Publication date: Available online 20 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Panduka B. Koswatta, Sabha Kasiri, Jayanta Das, Arunoday Bhan, Heather M. Lima, Beatriz Garcia-Barboza, Nicole N. Khatibi, Muhammed Yousufuddin, Subhrangsu S. Mandal, Carl J. Lovely
The total synthesis of a number of representative natural products isolated from Leucetta and Clathrina sponges containing a polysubstituted 2-aminoimidazole are described. These syntheses take advantage of the site specific metallation reactions of 4,5-diiodoimidazoles resulting in the syntheses of three different classes of Leucetta derived natural products. The cytotoxicities of these natural products, along with several precursors in MCF7 cells were determined through an MTT growth assay. For comparative purposes a series of naphthimidazole-containing family members are included.

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Visual analytics dashboard to explore the relationship of unscheduled treatment interruptions and variations in airway management for children undergoing external beam radiation therapy

Publication date: Available online 20 January 2017
Source:Practical Radiation Oncology
Author(s): Pandora Chua, Christine Hill-Kayser, Luis M. Ahumada, Ali Jalal, Allan F. Simpao, Arul M. Lingappan, Abbas Jawad, Mohamed A. Rehman, Jorge A. Gálvez




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What are appropriate physics manuscripts for submission to the Practical Radiation Oncology journal?

Publication date: Available online 20 January 2017
Source:Practical Radiation Oncology
Author(s): Todd Pawlicki, James Chow, Sonja Dieterich, Geoffrey Hugo




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Real time intraoperative evaluation of implant quality and dose correction during prostate brachytherapy consistently improves target coverage using a novel image fusion and optimization program

Publication date: Available online 20 January 2017
Source:Practical Radiation Oncology
Author(s): Michael J. Zelefsky, Gilad N. Cohen, Amandeep S. Taggar, Marisa Kollmeier, Sean McBride, Gig Mageras, Marco Zaider
PurposeTo describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion–based treatment-planning program.Materials and MethodsTwenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone-beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, and re-imported into the planning system and re-contoured. Dose distributions were re-calculated based upon actual implanted seed coordinates and re-contoured ultrasound images and reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed and anesthesia was reversed.ResultsWhen the intraoperative ultrasound–based quality assurance assessment was performed after seed placement, the median V100 was 93% [range, 74% to 98%]. Prior to seed correction, 23% (6/26) of cases were noted to have V100<90%. Based on this intraoperative assessment and re-planning, additional seeds based on the re-plan were placed into dose-deficient regions within the target to improve target dose distributions. Post-correction, the median V100 was 97% [range, 93% to 99%]. Following intraoperative dose corrections, all implants achieved V100>90%.ConclusionsIn these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies prior to anesthesia reversal. When applied, this approach should significantly reduce intraoperative errors and chances for suboptimal dose delivery during prostate brachytherapy.



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Irinotecan-induced radiation-recall myositis in a patient with metastatic breast cancer: a case report

Publication date: Available online 20 January 2017
Source:Practical Radiation Oncology
Author(s): Nitin Prabhakar, Uma Goyal, Victor Gonzalez




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“Acute and late toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated pelvic radiotherapy”

Publication date: Available online 20 January 2017
Source:Practical Radiation Oncology
Author(s): Sergio Faria, Russel Ruo, Fabio Cury, Marie Duclos, Luis Souhami
PurposeTo report acute and late toxicity rates in patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and moderate hypofractionated radiotherapy (HypoRT) to the prostate and nodal areas.Material and MethodsPatients with localized, high-risk prostate cancer were treated with a HypoRT regimen of 60Gy in 20 fractions (4weeks) to the prostate volume while the nodal areas received 44Gy in the same 20 fractions delivered with intensity modulated radiation therapy (IMRT) with a simultaneous integrated boost technique. ADT started 2–3months before HypoRT and was given to all patients. Acute and late toxicity was prospectively assessed and graded according to the Common Terminology Criteria for Adverse Events, version 3.Results105 patients treated between September/2010 and November/2013 were reviewed. Median follow up is 41months with 97% of patients followed for more than 26months. Median ADT duration was 18months. Acute grade 2 or higher gastrointestinal (GI) or genitourinary (GU) toxicity was seen in 18 (17%) and 19 (17%) patients respectively, with only 1 and 3 patients experiencing either a GI or GU acute grade 3 toxicity. The worst grade 2 or higher late GI and GU toxicity was seen in 7 (7%) and 8 (8%) patients, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rate of grade=2 GI and GU toxicity was 5% and 3%, respectively with no residual grade≥3 toxicity. The 48-month actuarial progression free survival is 82%.ConclusionADT with moderate HypoRT delivered with IMRT and an integrated simultaneous boost to the prostate (60Gy) and pelvic nodes (44Gy) in 20 fractions is feasible and well tolerated. This approach shortens treatment duration, is convenient to patients and the health system and its results support a randomized trial.SummaryWe report toxicity results of moderate hypofractionated radiotherapy delivered to the prostate (60Gy in 20 fractions) and pelvic nodal (44Gy in 20 fractions) volumes in patients with high-risk prostate cancer treated concurrently with androgen deprivation therapy. Toxicity was prospectively assessed. After a median follow up of 41months, this regimen proved to be feasible and well-tolerated.



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Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): S. Wurth, M. Capogrosso, S. Raspopovic, J. Gandar, G. Federici, N. Kinany, A. Cutrone, A. Piersigilli, N. Pavlova, R. Guiet, G. Taverni, J. Rigosa, P. Shkorbatova, X. Navarro, Q. Barraud, G. Courtine, S. Micera
Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes in the electrical properties of actively used intra-neural electrodes, highlighting functional stability of polyimide-based implants over more than six months. These results are essential for refining and validating these implants and open a realistic pathway for long-term clinical applications in humans.



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In vivo imaging of β-galactosidase stimulated activity in hepatocellular carcinoma using ligand-targeted fluorescent probe

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Eun-Joong Kim, Rajesh Kumar, Amit Sharma, Byungkwon Yoon, Hyun Min Kim, Hyunseung Lee, Kwan Soo Hong, Jong Seung Kim
Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe (DCDHF-βgal) for the sensitive detection, and in vivo visualization of β-galactosidase in hepatocyte HepG2 cells and its xenograft model. As a model system for in vivo targeted imaging, DCDHF-βgal possessing galactose unit selectively target hepatocyte and monitor the β-galactosidase activity with deep tissue penetration, and low background interference. DCDHF-βgal was activated by intracellular β-galactosidases as the driving force for the release of NIR fluorophore, thereby exhibiting ratiometric optical response. Initial fluorescence emission measured at 615 nm was changed to fluorescence at 665 nm upon activation of DCDHF-βgal with β-galactosidase. Ratiometric fluorescence detection of β-galactosidase was also observed in hepatocellular carcinoma cells and tumor xenograft. The noninvasive in vivo optical imaging facilitated by targeted and enzyme-activated imaging agent would be useful in various biomedical and diagnostic applications.



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Tuning physical properties and BMP-2 release rates of injectable hydrogel systems for an optimal bone regeneration effect

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Bo-Bae Seo, Jeong-Tae Koh, Soo-Chang Song
For a substance to be used as a drug delivery carrier and tissue inducible material for a target disease, its drug release rate and physical properties should be optimized to facilitate the healing process. We developed multi-tunable hydrogel systems with various physical properties and release behaviors to determine the optimal conditions for bone regeneration. Five injectable poly(phosphazene) hydrogels were developed with different types and amounts of anionic side-chains. The five polymer hydrogels showed considerably different in vitro and in vivo performances for sol-gel phase transition, dissolution/degradation, water uptake, and pore size. Furthermore, bone morphogenetic protein-2 (BMP-2) was loaded into the polymer hydrogels by forming nano-sized ionic-complexes with each polymer. The five types of nanocomplex hydrogels showed completely different BMP-2 release rates. By administering each nanocomplex hydrogel to mouse calvarial, we identified the most adapted nanocomplex hydrogel system for effective bone regeneration. The BMP-2 release rate was the most important factor in effective bone regeneration. Finally, the bone regeneration effect of the optimized hydrogel system was investigated in a critical-sized calvarial defect model.



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Tailoring polymeric hybrid micelles with lymph node targeting ability to improve the potency of cancer vaccines

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Qin Zeng, Hanmei Li, Hao Jiang, Jiao Yu, Ying Wang, Huan Ke, Tao Gong, Zhirong Zhang, Xun Sun
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions. We successfully encapsulate melanoma antigen peptide Trp2 and Toll-like receptor-9 (TLR-9) agonist CpG ODN into HMs with a size of sub-30 nm. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by simply adjusting the molar ratio of PEG-PE and PSA. Our results demonstrated the optimized HMs with an equal mol of PEG-PE and PSA can potently target proximal LNs where their cargos are efficiently internalized by DCs. Furthermore, HMs mediated Trp2/CpG delivery system greatly expands antigen specific cytotoxic T lymphocytes (CTLs) and offers a strong anti-tumor effect in a lung metastatic melanoma model.



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Editorial board

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Publication date: March 2017
Source:Biomaterials, Volume 121





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ASCIA News

ASCIA News

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    Aug 10, 2016:  ASCIA has released updated Action Plans for Anaphylaxis and Allergic Reactions on its website: http://ift.tt/1yS3Z48 The main changes are an increased emphasis of key messages, inclusion of images to show how to position a person with anaphylaxi...
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Synthesis of high crystalline syndiotactic 1,2-polybutadienes and study on their reinforcing effect on cis-1,4 polybutadiene

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Weijing Pan, Huafeng Chen, Jingshan Mu, Wei Li, Feng Jiang, Gengsheng Weng, Yanming Hu, Dirong Gong, Xuequan Zhang
A novel compound diethyl acetylphosphonate has been explored as efficient additive in iron based catalyst for stereo-polymerization of 1,3-butadiene to afford high crystalline 1,2-syndiotactic polybutadiene. Excellent 1,2 selectivity in range of 91.0–98.4% with controllable crystallinity has been achieved at high catalytic efficiency in wide ranges of cocatalyst and additive feeding as well as at large temperature scope. As reinforcing agent, two crystalline polymers differing in crystallinity 4.4% and 51.9% are blended and co-cured with cis-1,4 polybutadiene (PB) with 10 wt-%, providing samples PB1 and PB2, respectively. SEM from the sample fracturesurface shows the s-PBD particles are intimately mixed and homogeneously dispersed in PB matrix due to the strong interfacial interaction. The analysis of the mechanical properties of sample PB2 finds the tensile strength of increases by one-fold and the elongation at break increases by two-fold when head to head comparison to those of the CB filled PB, while the shear modulus G′ and loss factor (tan δ) are as good as those charged with CB. These results highlight the role of s-PBD as reinforcing agent of PB rubber, yielding high performance rubber materials with improved mechanical properties.

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Design and synthesis of polyaniline-grafted reduced graphene oxide via azobenzene pendants for high-performance supercapacitors

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Umashankar Male, Jeevan Kumar Reddy Modigunta, Do Sung Huh
To increase the pseudo-capacitance and cycle stability of polyaniline (PANI), PANI was covalently attached to reduced graphene oxide (rGO) via azobenzene (Azo) units. The rGO-Azo composite was first synthesized and subsequently used for the in situ chemical polymerization of aniline to form PANI-rGO-Azo composites. The Azo units on rGO functioned as spacers to prevent the agglomeration of rGO and increase the solubility of rGO to assist in the in situ polymerization of aniline to form PANI-rGO-Azo composite. The Azo units act as linkers for the covalent attachment of PANI chains to graphene, thereby enhance the overall performance of the composite materials. The electrochemical properties of the composites were evaluated by fabricating symmetric two-electrode cell configuration and also compared with three electrode system. The charge transfer resistance of PANI is reduced from 6.6 Ω to 2.9 Ω, by grafting PANI onto rGO-Azo. The specific capacitance of PANI-rGO-Azo (328 F g-1) is higher than that of PANI (270 F g-1) and rGO-Azo (114 F g-1). The electrochemical performance of PANI was enhanced by grafting of PANI onto rGO-Azo.

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Process induced alignment of gold nano-rods (GNRs) in thermoplastic polymer composites with tailored optical properties

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Devon A. Boyne, Alice M. Savage, Mark H. Griep, Frederick L. Beyer, Joshua A. Orlicki
Manipulation of the electronic and optical properties of plasmonic nanomaterials offers unique and exciting opportunities for several fields including opto-electronics, bio-medical engineering and photovoltaics. In particular, gold nanorods (GNR) represent a class of plasmonic nanomaterials that provide tunable optical properties from the visible to the near infrared regime. Herein, we have developed a highly effective method to prepare polymer nanocomposites (PNCs) doped with GNR additives utilizing extrusion and injection molding. A key outcome is that the process is amenable to scalable manufacturing and can produce highly reproducible PNCs with excellent optical properties. The resultant PNCs display good particle dispersion, minimal aggregation and a high retention of the optical properties as confirmed by UV-Vis spectroscopy and transmission electron microscopy. The nano-additives are incorporated into different thermoplastics to demonstrate the versatility of this method for different matrices and to demonstrate stability over the extrusion processing temperature range (235–335 °C). Furthermore, the tractability of this method is demonstrated by incorporating GNRs with different morphologies (aspect ratio, stabilizing layer, etc.). Finally, partial flow-induced alignment is demonstrated, the degree of which is modulated by the length and monodispersity of the GNR nano-additive. Ultimately, we report an optimized methodology to produce high quality GNR-PNCs with tailorable optical properties that can be adapted for scalable manufacturing.

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Amphiphilic silsesquioxane nanoparticles by hydrolytic condensation of Y-shaped triethoxysilanes having hydroxyl and fluoroalkyl groups: Synthesis, self-assembly, and surface properties

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Ryo Koizumi, Tetsuya Kimura, Kazuhiro Nakabayashi, Hideharu Mori
Two Y-shaped molecules combining two dissimilar (hydrophilic and hydrophobic) units with a reactive triethoxysilane moiety were synthesized by Michael addition reaction of (aminopropyl)triethoxysilane with 2-hydroxyethyl acrylate (HEA), followed by the addition of 2,2,2-trifluoroethyl acrylate (TFEA) or 1H,1H,5H-octafluoropentyl acrylate (OFPA). Hydrolytic condensations of the Y-shaped triethoxysilane precursors proceeded as homogeneous systems in acetone in presence of the acidic catalyst to afford amphiphilic silsesquioxane nanoparticles (SQ-NPs) having hydroxyl and fluoroalkyl groups (HEA/TFEA-SQ and HEA/OFPA-SQ). Scanning force microscope (SFM), X-ray diffraction (XRD), and size-exclusion chromatography (SEC) measurements indicated the formation of nanoparticles (average particle diameter is about 2.0 nm) with reasonable molecular weights and low dispersities (Mn = 5100-5400, Mw/Mn = 1.22–1.36) without aggregation. Characteristic assembled structures and surface properties of the amphiphilic SQ-NPs in different solvents were also evaluated. Flexible self-standing films were obtained from the amphiphilic SQ-NPs without any additional compounds, which are due to intermolecular hydrogen bondings.

Graphical abstract

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Polygonum multiflorum Radix extract protects human foreskin melanocytes from oxidative stress in vitro and potentiates hair follicle pigmentation ex vivo

Abstract

Objective

To examine the ability of an extract from traditional Chinese medicine, Polygonum multiflorum Radix, to protect melanocyte viability from oxidative stress, a key mechanism in the initiation and progression of hair greying.

Methods

To assess the antioxidant capacity of Polygonum multiflorum Radix extract, primary human foreskin melanocytes were treated with a commercially available Polygonum multiflorum Radix extract added to culture medium and exposed to hydrogen peroxide (H2O2), using intracellular reactive oxygen species concentrations and glutathione/protein ratios as endpoints. To improve solubility for cosmetic uses, a new Polygonum multiflorum Radix extract was derived. As hair graying is the consequence of melanocyte disappearance in an oxidative stress environment, we checked if the anti-oxidant capacity of the new Polygonum multiflorum Radix extract could preserve melanocyte viability in response to H2O2-induced oxidative stress, and preserve pigmentation within ex vivo human hair follicles.

Results

In vitro treatment of primary human foreskin melanocytes with traditional available Polygonum multiflorum Radix extract resulted in decreased intracellular ROS accumulation in response to H2O2 exposure with a concomitant preservation of glutathione to protein ratio, consistent with a protective response against H2O2 exposure and demonstrating the promise of this extract for protecting melanocytes against oxidative stress. Melanocytes treated with the improved Polygonum multiflorum Radix extract exhibited attenuated H2O2-induced cell death, demonstrating a clear cytoprotective effect. Treatment of ex vivo human hair follicles with the improved Polygonum multiflorum Radix extract resulted in a higher level of melanin compared to vehicle-treated controls, demonstrating an ex vivo protective effect on hair pigmentation.

Conclusion

Polygonum multiflorum Radix extract protects in vitro primary human foreskin melanocytes from the deleterious effects of H2O2-exposure and improves pigmentation within ex vivo human hair follicles, demonstrating the utility of Polygonum multiflorum Radix extract as a potential active ingredient for the protection of melanocytes against premature death. This data provides in vitro mechanistic evidence consistent with existing in vivo studies for the use of Polygonum multiflorum Radix extract as a strategy for the prevention of oxidative-stress induced hair greying, in line with traditional Polygonum multiflorum Radix uses.

This article is protected by copyright. All rights reserved.



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Neural Representations of Belief Concepts: A Representational Similarity Approach to Social Semantics

The present experiment identified neural regions that represent a class of concepts that are independent of perceptual or sensory attributes. During functional magnetic resonance imaging scanning, participants viewed names of social groups (e.g. Atheists, Evangelicals, and Economists) and performed a one-back similarity judgment according to 1 of 2 dimensions of belief attributes: political orientation (Liberal to Conservative) or spiritualism (Spiritualist to Materialist). By generalizing across a wide variety of social groups that possess these beliefs, these attribute concepts did not coincide with any specific sensory quality, allowing us to target conceptual, rather than perceptual, representations. Multi-voxel pattern searchlight analysis was used to identify regions in which activation patterns distinguished the 2 ends of both dimensions: Conservative from Liberal social groups when participants focused on the political orientation dimension, and spiritual from Materialist groups when participants focused on the spiritualism dimension. A cluster in right precuneus exhibited such a pattern, indicating that it carries information about belief-attribute concepts and forms part of semantic memory—perhaps a component particularly concerned with psychological traits. This region did not overlap with the theory of mind network, which engaged nearby, but distinct, parts of precuneus. These findings have implications for the neural organization of conceptual knowledge, especially the understanding of social groups.



http://ift.tt/2iLPkaB

Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): S. Wurth, M. Capogrosso, S. Raspopovic, J. Gandar, G. Federici, N. Kinany, A. Cutrone, A. Piersigilli, N. Pavlova, R. Guiet, G. Taverni, J. Rigosa, P. Shkorbatova, X. Navarro, Q. Barraud, G. Courtine, S. Micera
Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes in the electrical properties of actively used intra-neural electrodes, highlighting functional stability of polyimide-based implants over more than six months. These results are essential for refining and validating these implants and open a realistic pathway for long-term clinical applications in humans.



http://ift.tt/2jGbzOo

In vivo imaging of β-galactosidase stimulated activity in hepatocellular carcinoma using ligand-targeted fluorescent probe

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Eun-Joong Kim, Rajesh Kumar, Amit Sharma, Byungkwon Yoon, Hyun Min Kim, Hyunseung Lee, Kwan Soo Hong, Jong Seung Kim
Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe (DCDHF-βgal) for the sensitive detection, and in vivo visualization of β-galactosidase in hepatocyte HepG2 cells and its xenograft model. As a model system for in vivo targeted imaging, DCDHF-βgal possessing galactose unit selectively target hepatocyte and monitor the β-galactosidase activity with deep tissue penetration, and low background interference. DCDHF-βgal was activated by intracellular β-galactosidases as the driving force for the release of NIR fluorophore, thereby exhibiting ratiometric optical response. Initial fluorescence emission measured at 615 nm was changed to fluorescence at 665 nm upon activation of DCDHF-βgal with β-galactosidase. Ratiometric fluorescence detection of β-galactosidase was also observed in hepatocellular carcinoma cells and tumor xenograft. The noninvasive in vivo optical imaging facilitated by targeted and enzyme-activated imaging agent would be useful in various biomedical and diagnostic applications.



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In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Xiaoqiang Chen, Dayoung Lee, Sungsook Yu, Gyoungmi Kim, Songyi Lee, Yejin Cho, Haengdueng Jeong, Ki Taek Nam, Juyoung Yoon
The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.

Graphical abstract

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Tuning physical properties and BMP-2 release rates of injectable hydrogel systems for an optimal bone regeneration effect

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Bo-Bae Seo, Jeong-Tae Koh, Soo-Chang Song
For a substance to be used as a drug delivery carrier and tissue inducible material for a target disease, its drug release rate and physical properties should be optimized to facilitate the healing process. We developed multi-tunable hydrogel systems with various physical properties and release behaviors to determine the optimal conditions for bone regeneration. Five injectable poly(phosphazene) hydrogels were developed with different types and amounts of anionic side-chains. The five polymer hydrogels showed considerably different in vitro and in vivo performances for sol-gel phase transition, dissolution/degradation, water uptake, and pore size. Furthermore, bone morphogenetic protein-2 (BMP-2) was loaded into the polymer hydrogels by forming nano-sized ionic-complexes with each polymer. The five types of nanocomplex hydrogels showed completely different BMP-2 release rates. By administering each nanocomplex hydrogel to mouse calvarial, we identified the most adapted nanocomplex hydrogel system for effective bone regeneration. The BMP-2 release rate was the most important factor in effective bone regeneration. Finally, the bone regeneration effect of the optimized hydrogel system was investigated in a critical-sized calvarial defect model.



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Tailoring polymeric hybrid micelles with lymph node targeting ability to improve the potency of cancer vaccines

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Qin Zeng, Hanmei Li, Hao Jiang, Jiao Yu, Ying Wang, Huan Ke, Tao Gong, Zhirong Zhang, Xun Sun
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions. We successfully encapsulate melanoma antigen peptide Trp2 and Toll-like receptor-9 (TLR-9) agonist CpG ODN into HMs with a size of sub-30 nm. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by simply adjusting the molar ratio of PEG-PE and PSA. Our results demonstrated the optimized HMs with an equal mol of PEG-PE and PSA can potently target proximal LNs where their cargos are efficiently internalized by DCs. Furthermore, HMs mediated Trp2/CpG delivery system greatly expands antigen specific cytotoxic T lymphocytes (CTLs) and offers a strong anti-tumor effect in a lung metastatic melanoma model.



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Whatsapp: Improvement tool for surgical team communication

We read the article by Sidhoum et al. entitled "WhatsApp: Improvement tool for surgical team communication" with interest and commend them for highlighting strategies to improve communication within the surgical team.1

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Hypoxia and host pathogen responses

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Publication date: Available online 20 January 2017
Source:Microbes and Infection
Author(s): Sarah R. Walmsley, Jan Rupp




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Semi-automatic 3D morphological reconstruction of neurons with densely branching morphology: application to retinal AII amacrine cells imaged with multi-photon excitation microscopy

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Publication date: Available online 20 January 2017
Source:Journal of Neuroscience Methods
Author(s): Bas-Jan Zandt, Are Losnegård, Erlend Hodneland, Margaret Lin Veruki, Arvid Lundervold, Espen Hartveit
BackgroundAccurate reconstruction of the morphology of single neurons is important for morphometric studies and for developing compartmental models. However, manual morphological reconstruction can be extremely time-consuming and error-prone and algorithms for automatic reconstruction can be challenged when applied to neurons with a high density of extensively branching processes.New methodWe present a procedure for semi-automatic reconstruction specifically adapted for densely branching neurons such as the AII amacrine cell found in mammalian retinas. We used whole cell recording to fill AII amacrine cells in rat retinal slices with fluorescent dyes and acquired digital image stacks with multi-photon excitation microscopy. Our reconstruction algorithm combines elements of existing procedures, with segmentation based on adaptive thresholding and reconstruction based on a minimal spanning tree. We improved this workflow with an algorithm that reconnects neuron segments that are disconnected after adaptive thresholding, using paths extracted from the image stacks with the Fast Marching method.ResultsBy reducing the likelihood that disconnected segments were incorrectly connected to neighboring segments, our procedure generated excellent morphological reconstructions of AII amacrine cells.Comparison with existingmethods Reconstructing an AII amacrine cell required about 2hrs computing time, compared to 2–4days for manual reconstruction. To evaluate the performance of our method relative to manual reconstruction, we performed detailed analysis using a measure of tree structure similarity (DIADEM score), the degree of projection area overlap (Dice coefficient), and branch statistics.ConclusionsWe expect our procedure to be generally useful for morphological reconstruction of neurons filled with fluorescent dyes.



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Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas

Abstract

Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.



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Gadolinium Contrast Enhancement Improves Confidence in Diagnosing Recurrent Soft Tissue Sarcoma by MRI

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Publication date: Available online 20 January 2017
Source:Academic Radiology
Author(s): Shinn-Huey S. Chou, Daniel S. Hippe, Amie Y. Lee, Kurt Scherer, Jack A. Porrino, Darin J. Davidson, Felix S. Chew, Alice S. Ha
Rationale and ObjectivesTo determine how utilization of postgadolinium magnetic resonance imaging (MRI) influenced reader accuracy and confidence at identifying postoperative soft tissue sarcoma (STS) recurrence among readers with various levels of expertise.Materials and MethodsThis retrospective study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. Postoperative MRI from 26 patients with prior STS resection (13 patients with confirmed recurrence, 13 without recurrence) was reviewed. Four blinded readers of varying expertise (radiology resident, fellow, attending, and orthopedic oncologist) initially evaluated only the precontrast images and rated each MRI for recurrence on a 5-point confidence scale. Assessment was repeated with the addition of contrast-enhanced sequences. Diagnostic accuracy based on confidence ratings was evaluated using the area under the receiver operating characteristic curve (AUC). Changes in confidence ratings were calculated using Wilcoxon signed-rank test.ResultsAll readers demonstrated good diagnostic accuracy both with and without contrast-enhanced images (AUC >0.98 for each reader). When contrast-enhanced images were made available, the resident recorded improved confidence with both assigning (P = 0.031) and excluding recurrence (P = 0.006); the fellow showed improved confidence only with assigning recurrence (P = 0.015); and the surgeon showed improved confidence in excluding recurrence (P = 0.003). The addition of contrast-enhanced images did not significantly influence the diagnostic confidence of the attending radiologist.ConclusionsDiagnostic accuracy of MRI was excellent in evaluating postoperative STS recurrence, and reader confidence improved depending on expertise when postgadolinium imaging was included in the assessment.



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Radiological characterization of the ancient Roman tuff-pozzolana underground quarry in Orvieto (Italy): A natural laboratory to revisit the interactions between radionuclides and aerosols

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Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): C. Nuccetelli, R. Trevisi, F. Leonardi, M. Ampollini, F. Cardellini, S. Tonnarini, K. Kovler, C. Vargas Trassiera
Orvieto (Italy) has a large network of underground tunnels quarried to extract tuff and pozzolana by Etruscans and Romans. One of these tunnels was chosen as natural laboratory to compare different radiation measurement and dose assessment methods. Indeed, tuff and pozzolana are very rich in natural radioactivity and are interesting from the radiation protection point of view since they are still used as building materials. In order to characterize this site an in situ experimental procedure was followed. It consisted in measurements carried out with different instruments: two portable gamma ray spectrometers, two gamma dose rate meters, two radon monitors and one two channel working level monitor. Samples of tuff and pozzolana stones were also collected to be measured with gamma spectrometry in laboratory. Due to the high content of 238U, 232Th (more than 200 Bq kg−1 for both radionuclides) and 40K (more than 2000 Bq kg−1) of tuff and pozzolana, elevated levels of exposure to natural radioactivity were found: indeed, with different instruments and approach, a gamma dose rate of about 1 μGy h−1 and an average radon concentration of about 10,000 Bq m−3, with a Potential Alpha Energy Concentration (PAEC) of 288 MeV cm−3, were measured. The radiological characteristics of Orvieto underground quarry make it a perfect site for "in field" intercomparisons of different measurement and dose assessment methods.



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Soil-soil solution distribution coefficient of soil organic matter is a key factor for that of radioiodide in surface and subsurface soils

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Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Yusuke Unno, Hirofumi Tsukada, Akira Takeda, Yuichi Takaku, Shun'ichi Hisamatsu
We investigated the vertical distribution of the soil–soil-solution distribution coefficients (Kd) of 125I, 137Cs, and 85Sr in organic-rich surface soil and organic-poor subsurface soil of a pasture and an urban forest near a spent-nuclear-fuel reprocessing plant in Rokkasho, Japan. Kd of 137Cs was highly correlated with water-extractable K+. Kd of 85Sr was highly correlated with water-extractable Ca2+ and SOC. Kd of 125I was low in organic-rich surface soil, high slightly below the surface, and lowest in the deepest soil. This kinked distribution pattern differed from the gradual decrease of the other radionuclides. The thickness of the high-125IKd middle layer (i.e., with high radioiodide retention ability) differed between sites. Kd of 125I was significantly correlated with Kd of soil organic carbon. Our results also showed that the layer thickness is controlled by the ratio of Kd-OC between surface and subsurface soils. This finding suggests that the addition of SOC might prevent further radioiodide migration down the soil profile. As far as we know, this is the first report to show a strong correlation of a soil characteristic with Kd of 125I. Further study is needed to clarify how radioiodide is retained and migrates in soil.



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Editorial board

Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168





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Special issue: Naturally radioactivity in construction

Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): Konstantin Kovler, Wouter Schroeyers




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Concentrations of 226Ra, 232Th and 40K in industrial kaolinized granite

Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): Nataša Todorović, Jan Hansman, Dušan Mrđa, Jovana Nikolov, Richárd Kardos, Miodrag Krmar
Activity concentrations of 226Ra, 232Th and 40K in 120 kaolinized granite samples imported in Serbia from the Motajica mine, Bosnia and Herzegovina, were measured. The 226Ra concentration ranged from 61 to 319 Bq kg−1, the 232Th from 44 to 272 Bq kg−1, and the 40K from 590 to 1470 Bq kg−1. The frequency distribution of 40K concentrations was near-Gaussian, where those of 226Ra and 232Th were right-skewed. In 6 samples, the gamma index, I, was higher than 2, which exceeds the exemption dose criterion (0.3 mSv y−1). The absorbed dose rate and annual effective doses for workers in the ceramic industries in Serbia who worked with kaolinized granite were below levels of concern.



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Radon exhalation study of manganese clay residue and usability in brick production

Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): Tibor Kovács, Amin Shahrokhi, Zoltán Sas, Tamás Vigh, János Somlai
The reuse of by-products and residue streams is an important topic due to environmental and financial aspects. Manganese clay is a residue of manganese ore processing and is generated in huge amounts. This residue may contain some radionuclides with elevated concentrations. In this study, the radon emanation features and the massic exhalation rate of the heat-treated manganese clay were determined with regard to brick production. From the manganese mud depository, 20 samples were collected and after homogenization radon exhalation characteristics were determined as a function of firing temperatures from 100 to 750 °C. The major naturally occurring radionuclides 40K, 226Ra and 232Th concentrations were 607 ± 34, 52 ± 6 and 40 ± 5 Bq kg−1, respectively, comparable with normal clay samples. Similar to our previous studies a strong correlation was found between the internal structure and the radon emanation. The radon emanation coefficient decreased by ∼96% from 0.23 at 100 °C to 0.01 at 750 °C. The massic radon exhalation rate of samples fired at 750 °C reduced by 3% compared to samples fired at 100 °C. In light of the results, reusing of manganese clay as a brick additive is possible without any constraints.



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Radiological characterization and evaluation of high volume bauxite residue alkali activated concretes

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Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): Tom Croymans, Wouter Schroeyers, Pavel Krivenko, Oleksandr Kovalchuk, Anton Pasko, Mikael Hult, Gerd Marissens, Guillaume Lutter, Sonja Schreurs
Bauxite residue, also known as red mud, can be used as an aggregate in concrete products. The study involves the radiological characterization of different types of concretes containing bauxite residue from Ukraine. The activity concentrations of radionuclides from the 238U, 232Th decay series and 40K were determined for concrete mixture samples incorporating 30, 40, 50, 60, 75, 85 and 90% (by mass) of bauxite residue using gamma-ray spectrometry with a HPGe detector. The studied bauxite residue can, from a radiological point of view using activity concentration indexes developed by Markkanen, be used in concrete for building materials and in road construction, even in percentages reaching 90% (by mass). However, when also occupational exposure is considered it is recommended to incorporate less than 75% (by mass) of Ukrainian bauxite residue during the construction of buildings in order to keep the dose to workers below the dose criterion used by Radiation Protection (RP) 122 (0.3 mSv/a). Considering RP122 for evaluation of the total effective dose to workers no restrictions are required for the use of the Ukrainian bauxite residue in road construction.



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Alkali-activated concrete with Serbian fly ash and its radiological impact

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Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): Cristina Nuccetelli, Rosabianca Trevisi, Ivan Ignjatović, Jelena Dragaš
The present paper reports the results of a study on different types of fly ash from Serbian coal burning power plants and their potential use as a binder in alkali-activated concrete (AAC) depending on their radiological and mechanical properties. Five AAC mixtures with different types of coal burning fly ash and one type of blast furnace slag were designed. Measurements of the activity concentrations of 40K, 226Ra and 232Th were done both on concrete constituents (fly ash, blast furnace slag and aggregate) and on the five solid AAC samples. Experimental results were compared by using the activity concentration assessment tool for building materials - the activity concentration index I, as introduced by the EU Basic Safety Standards (CE, 2014). All five designed alkali-activated concretes comply with EU BSS screening requirements for indoor building materials. Finally, index I values were compared with the results of the application of a more accurate index - I(ρd), which accounts for thickness and density of building materials (Nuccetelli et al., 2015a). Considering the actual density and thickness of each concrete sample index - I(ρd) values are lower than index I values.As an appendix, a synthesis of main results concerning mechanical and chemical properties is provided.



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Radiological and material characterization of high volume fly ash concrete

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Publication date: March 2017
Source:Journal of Environmental Radioactivity, Volume 168
Author(s): I. Ignjatović, Z. Sas, J. Dragaš, J. Somlai, T. Kovács
The main goal of research presented in this paper was the material and radiological characterization of high volume fly ash concrete (HVFAC) in terms of determination of natural radionuclide content and radon emanation and exhalation coefficients. All concrete samples were made with a fly ash content between 50% and 70% of the total amount of cementitious materials from one coal burning power plant in Serbia. Physical (fresh and hardened concrete density) and mechanical properties (compressive strength, splitting tensile strength and modulus of elasticity) of concrete were tested. The radionuclide content (226Ra, 232Th and 40K) and radon massic exhalation of HVFAC samples were determined using gamma spectrometry. Determination of massic exhalation rates of HVFAC and its components using radon accumulation chamber techniques combined with a radon monitor was performed. The results show a beneficial effect of pozzolanic activity since the increase in fly ash content resulted in an increase in compressive strength of HVFAC by approximately 20% for the same mass of cement used in the mixtures. On the basis of the obtained radionuclide content of concrete components the I -indices of different HVFAC samples were calculated and compared with measured values (0.27–0.32), which were significantly below the recommended 1.0 index value. The prediction was relatively close to the measured values as the ratio between the calculated and measured I-index ranged between 0.89 and 1.14. Collected results of mechanical and radiological properties and performed calculations clearly prove that all 10 designed concretes with a certain type of fly ash are suitable for structural and non-structural applications both from a material and radiological point of view.



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Congenital Toxoplasmosis

Publication date: Available online 20 January 2017
Source:Pediatric Neurology
Author(s): Rahul Guha, Lauren Miley, Madison Aspiri, Radhika Dhamija




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Quantitative proteomics analysis reveals the tolerance of Mirabilis jalapa L. to petroleum contamination

Abstract

Petroleum is not only an important energy resource but is also a major soil pollutant. To gain better insight into the adaptability mechanism of Mirabilis jalapa to petroleum-contaminated soil, the protein profiles of M. jalapa root were investigated using label-free quantitative proteomics technique. After exposing to petroleum-contaminated soil for 24 h, 34 proteins significantly changed their protein abundance and most of the proteins increased in protein abundance (91.18%). Combined with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses as well as data from previous studies, our results revealed that M. jalapa enhanced tolerance to petroleum by changing antioxidation and detoxification, cell wall organization, amino acid and carbohydrate metabolism, transportation and protein process, and so on. These metabolism alterations could result in the production and secretion of low molecular carbohydrate, amino acid, and functional protein, which enhanced the bioavailability of petroleum and reducing the toxicity of the petroleum. Taken together, these results provided novel information for better understanding of the tolerance of M. jalapa to petroleum stress.



http://ift.tt/2iKNZAY

Modification of the 137 Cs, 90 Sr, and 60 Co transfer to wheat plantlets by NH 4 + fertilizers

Abstract

Inorganic fertilizers are used as agricultural countermeasures intended to inhibit the soil to plant transfer of radionuclides after a radioactive fallout. Two NH4+ fertilizers, diammonium phosphate (DAP) and NPK, were applied to soil contaminated with a mixture of radionuclides to analyze whether they modify the transfer of 137Cs, 90Sr, and 60Co and stable elements (K, Na, Ca, and Mg) to wheat plantlets grown under controlled laboratory conditions. DAP introduced NH4+ in the soil, which can increase 137Cs transfer, while NPK also introduced K+, which can decrease it. The application of DAP increased the accumulation of 137Cs in wheat plantlets with increasing application rate, so did the 137Cs/K in plantlets. Regarding the NPK application, the 137Cs increased in all treatments, but at maximum rate, the available K introduced by the fertilizer was probably able to partially satisfy the nutritional requirements of the wheat plantlet and the 137Cs decreased relative to the recommended rate. The 137Cs/K ratio in plantlet decreased with increasing NPK rates. The transfer of 90Sr increased with increasing DAP rate and only at the maximum NPK rate. The 60Co transfer only increased at the maximum application rates for DAP and NPK. These modifications should be considered when using these fertilizers as agricultural countermeasures.



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Dissipation and phytoremediation of polycyclic aromatic hydrocarbons in freshly spiked and long-term field-contaminated soils

Abstract

Pot experiments were used to compare the dissipation and phytoremediation effect of alfalfa (Medicago sativa L.) for polycyclic aromatic hydrocarbons (PAHs) in a freshly spiked soil and two field-contaminated soils with different soil organic carbon (SOC) contents (Anthrosols, 1.41% SOC; Phaeozems, 8.51% SOC). In spiked soils, the dissipation rates of phenanthrene and pyrene were greater than 99.5 and 94.3%, respectively, in planted treatments and 95.0 and 84.5%, respectively, in unplanted treatments. In field-contaminated Anthrosols, there were limited but significant reductions of 10.2 and 15.4% of total PAHs in unplanted and planted treatments, respectively. In field-contaminated Phaeozems, there were no significant reductions of total PAHs in either unplanted or planted treatments. A phytoremediation effect was observed for the spiked soils and the Anthrosols, but not for the Phaeozems. The results indicated that laboratory tests with spiked soils cannot reflect the real state of field-contaminated soils. Phytoremediation efficiency of PAHs in field-contaminated soils was mainly determined by the content of SOC. Phytoremediation alone has no effect on the removal of PAHs in field-contaminated soils with high SOC content.



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I know you can see me: social ATTENTION influences BODILY self-awareness

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Publication date: Available online 19 January 2017
Source:Biological Psychology
Author(s): Nesrine Hazem, Nathalie George, Matias Baltazar, Laurence Conty
It has recently been demonstrated that eye contact influences bodily self-awareness. Here, we investigated if the belief of being the target of another person's attention may also induce such influence. We created videos of an individual wearing two different pairs of sunglasses. We manipulated the participants to believe that they were in on-line connection with the individual and that one of the pairs of sunglasses was obstructed so that the individual could not see them through it. We demonstrated that the perception of an individual wearing see-through sunglasses, as compared to obstructed sunglasses or a low-level baseline condition, led to a greater correlation between the participants' rating of the intensity of their bodily reactions and their skin conductance response to emotional pictures. This shows that the belief to be watched by another social agent increases bodily self-awareness and further suggests that such belief is embedded in direct gaze perception.



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On the neural mechanisms underlying the protective function of retroactive cuing against perceptual interference: Evidence by event-related potentials of the EEG

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Publication date: Available online 20 January 2017
Source:Biological Psychology
Author(s): Daniel Schneider, Anna Barth, Stephan Getzmann, Edmund Wascher
This EEG study investigated the protective effect of retroactive attentional focusing on working memory. To this effect, we used a visuo-spatial working memory task and presented block-wise distractor displays after working memory contents had been updated by means of a retroactive cue (retro-cue). Retroactive attention attenuated the interfering effect of distractors on memory precision. The reduction of working memory load by means of a selective retro-cue was reflected by a decline of a negative slow wave over parietal sites. Posterior N1 to the distractor was reduced following a selective retro-cue compared to a neutral retro-cue condition, most notably at left hemispheric sites. P3b referred to the distractor was suppressed completely only following a selective retro-cue. This suggests that focusing on only a subset of visuo-spatial information represented in working memory releases cognitive resources for preventing the in-depth processing of subsequently irrelevant visual events, thereby inhibiting their transfer into working memory.



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Soft tissue substitutes in non-root coverage procedures: a systematic review and meta-analysis

Abstract

Objectives

The present systematic review compared the effectiveness of soft tissue substitutes (STSs) and autogenous free gingival grafts (FGGs) in non-root-coverage procedures to increase keratinized tissue (KT) width around teeth.

Materials and methods

Included studies fulfilled the following main eligibility criteria: (a) preclinical in vivo or human controlled trials using FGG as control, (b) non-root-coverage procedures, and (c) assessment of KT width. Meta-analysis was performed on the gain in KT width (primary outcome variable) and several secondary variables.

Results

Eight human trials with short observation time evaluating five different STSs were identified. FGG yielded consistently significantly (p < 0.001) larger increase in KT width irrespective whether the comparison regarded an acellular matrix or a tissue-engineered STS. Further, FGG yielded consistently ≥2 mm KT width postoperatively, while use of STS did not, in the few studies reporting on this outcome. On the other hand, STSs resulted in significantly better aesthetic outcomes and received greater patient preference (p < 0.001).

Conclusions

Based on relatively limited evidence, in non-root-coverage procedures, FGG (1) resulted consistently in significantly larger increase in KT width compared to STS and (2) yielded consistently ≥2 mm KT width postoperatively, while STSs did not. STSs yielded significantly better aesthetic outcomes, received greater patient preference, and appeared safe.

Clinical relevance

Larger and more predictable increase in KT width is achieved with FGG, but STSs may be considered when aesthetics is important. Clinical studies reporting relevant posttreatment outcomes, e.g., postop KT width ≥2 mm, on the long-term (>6 months) are warranted.



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Xenobiotic transporters and kidney injury

Publication date: Available online 20 January 2017
Source:Advanced Drug Delivery Reviews
Author(s): Blessy George, Dahea You, Melanie S. Joy, Lauren M. Aleksunes
Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarbon solvents, the herbicide paraquat, the fungal toxin ochratoxin, and heavy metals) as well as pharmaceuticals (certain beta-lactam antibiotics, antiviral drugs, and chemotherapeutic drugs). This review explores the mechanisms by which transporters mediate the entry and exit of toxicants from renal tubule cells and influence the degree of kidney injury. Delineating how transport proteins regulate the renal accumulation of toxicants is critical for understanding the likelihood of nephrotoxicity resulting from competition for excretion or genetic polymorphisms that affect transporter function.

Graphical abstract

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Mitteilungen der Deutschen Gesellschaft für Kieferorthopädie



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Trends in Patient Safety of Intact Abdominal Aortic Aneurysm Repair: German Registry Data on 36,594 Procedures

Publication date: Available online 19 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): M. Trenner, B. Haller, M. Storck, B. Reutersberg, M.A. Kallmayer, H.-H. Eckstein
Objective/BackgroundThe study aim was to determine whether patient safety for non-ruptured abdominal aortic aneurysm (nrAAA) repair has changed between 1999 and 2010 in a large German cohort.MethodsThe data source was the prospective quality assurance registry of the German Vascular Society from 1999 to 2010. Patient characteristics, surgical techniques (open aortic repair [OAR], endovascular aortic repair [EVAR]), procedural time and outcomes, including the length of hospital stay (LOS), were analysed using the Cochran–Armitage test for binary parameters and Spearman's correlation coefficient for quantitative parameters.ResultsA total of 36,594 operations (23,037 OAR, 13,557 EVAR) for infrarenal nrAAA in 201 hospitals in Germany were investigated. Patients' mean age increased from 69.6 to 72.0 years (p < .001). The rate of patients with American Society of Anesthesiologists scores of 3 or 4 increased (p < .001). Use of EVAR increased (1999: 16.7%; 2010: 62.7%; p < .001), and since 2009, EVAR has been more frequently used than OAR. The overall in hospital mortality decreased from 3.1% in 1999 to 2.3% in 2010 (p < .001). There were no temporal trends for mortality rates for EVAR (p = .233) or OAR (p = .281) when considered separately. Cardiac (1999: 8.1%; 2010: 5.1%; p < .001) and pulmonary (1999: 7.8%; 2010: 4.8%; p < .001) complications decreased. The rate of post-operative renal failure increased (1999: 3.6%; 2010 4.1%; p = .017), without increasing the rate of patients needing dialysis (1999: 1.7%; 2010: 1.7%; p = .171). The median LOS decreased from 17 days in 1999 to 10 days in 2010 (p < .001).ConclusionThis study shows significantly improved post-procedural in hospital outcomes and decreased use of resources for nrAAA repair. This trend can probably be attributed to the implementation of EVAR as a standard technique, but some trends could also possibly be explained by a change in the remuneration system. The main limitation of the registry is the lack of internal and external validation. However, in hospital patient safety for AAA repair seems to have improved significantly in the participating hospitals.



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A Multicentre Trial of Patient specific Rehearsal Prior to EVAR: Impact on Procedural Planning and Team Performance

Publication date: Available online 20 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): L. Desender, I. Van Herzeele, M. Lachat, J. Duchateau, C. Bicknell, J. Teijink, J. Heyligers, F. Vermassen
ObjectivePatient specific rehearsal (PsR) prior to endovascular aneurysm repair (EVAR) enables the endovascular team to practice and evaluate the procedure prior to treating the real patient. This multicentre trial aimed to evaluate the utility of PsR prior to EVAR as a pre-operative planning and briefing tool.Material and methodsPatients with an aneurysm suitable for EVAR were randomised to pre-operative or post-operative PsR. Before and after the PsR, the lead implanter completed a questionnaire to identify any deviation from the initial treatment plan. All team members completed a questionnaire evaluating realism, technical issues, and human factor aspects pertinent to PsR. Technical and human factor skills, and technical and clinical success rates were compared between the randomised groups.Results100 patients were enrolled between September 2012 and June 2014. The plan to visualise proximal and distal landing zones was adapted in 27/50 (54%) and 38/50 (76%) cases, respectively. The choice of the main body, contralateral limb, or iliac extensions was adjusted in 8/50 (16%), 17/50 (34%), and 14/50 (28%) cases, respectively. At least one of the abovementioned parameters was changed in 44/50 (88%) cases. For 100 EVAR cases, 199 subjective questionnaires post-PsR were completed. PsR was considered to be useful for selecting the optimal C-arm angulation (median 4, IQR 4-5) and was recognised as a helpful tool for team preparation (median 4, IQR 4-4), to improve communication (median 4, IQR 3-4), and encourage confidence (median 4, IQR 3-4). Technical and human factor skills and technical and initial clinical success rates were similar between the randomisation groups.ConclusionPsR prior to EVAR has a significant impact on the treatment plan and may be useful as a pre-operative planning and briefing tool. Subjective ratings indicate that this technology may facilitate planning of optimal C-arm angulation and improve non-technical skills. Trial registration: URL://www.clinicaltrials.gov. Unique identifier: NCT01632631.



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Temporal detection and analysis of guideline interactions

Publication date: Available online 20 January 2017
Source:Artificial Intelligence in Medicine
Author(s): Luca Anselma, Luca Piovesan, Paolo Terenziani
BackgroundClinical practice guidelines (CPGs) are assuming a major role in the medical area, to grant the quality of medical assistance, supporting physicians with evidence-based information of interventions in the treatment of single pathologies. The treatment of patients affected by multiple diseases (comorbid patients) is one of the main challenges for the modern healthcare. It requires the development of new methodologies, supporting physicians in the treatment of interactions between CPGs. Several approaches have started to face such a challenging problem. However, they suffer from a substantial limitation: they do not take into account the temporal dimension. Indeed, practically speaking, interactions occur in time. For instance, the effects of two actions taken from different guidelines may potentially conflict, but practical conflicts happen only if the times of execution of such actions are such that their effects overlap in time.ObjectivesWe aim at devising a methodology to detect and analyse interactions between CPGs that considers the temporal dimension.MethodsIn this paper, we first extend our previous ontological model to deal with the fact that actions, goals, effects and interactions occur in time, and to model both qualitative and quantitative temporal constraints between them. Then, we identify different application scenarios, and, for each of them, we propose different types of facilities for user physicians, useful to support the temporal detection of interactions.ResultsWe provide a modular approach in which different Artificial Intelligence temporal reasoning techniques, based on temporal constraint propagation, are widely exploited to provide users with such facilities. We applied our methodology to two cases of comorbidities, using simplified versions of CPGs.ConclusionWe propose an innovative approach to the detection and analysis of interactions between CPGs considering different sources of temporal information (CPGs, ontological knowledge and execution logs), which is the first one in the literature that takes into account the temporal issues, and accounts for different application scenarios.



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Generation of human islet-specific regulatory T cells by TCR gene transfer

Publication date: Available online 20 January 2017
Source:Journal of Autoimmunity
Author(s): Caroline M. Hull, Lauren E. Nickolay, Megan Estorninho, Max W. Richardson, James L. Riley, Mark Peakman, John Maher, Timothy I.M. Tree
Based on the success in animal models of type 1 diabetes (T1D), clinical trials of adoptive regulatory T cell (Treg) therapy are underway using ex vivo expanded polyclonal Tregs. However, pre-clinical data also demonstrate that islet-specific Tregs are more potent than polyclonal Tregs at reversing T1D. Translation of this approach into man will require methods to generate large populations of islet-specific Tregs which, to date, has proved to be a major hurdle. Here we demonstrate the feasibility of lentiviral-mediated T cell receptor (TCR) gene transfer to confer antigen specificity on polyclonal human Tregs. Targeting has been achieved using TCRs isolated from human islet-specific and viral-specific CD4+ T cell clones. Engineered T cells demonstrated expression of ectopically-delivered TCRs, resulting in endowment of cognate antigen-specific responses. This enabled antigen-specific suppression at increased potency compared to polyclonal Tregs. However, cells transduced with islet-specific TCRs were less responsive to cognate antigen than viral-specific TCRs, and in some cases, required additional methods to isolate functional antigen-specific Tregs. This study demonstrates the potential of TCR gene transfer to develop islet-specific Treg therapies for effective treatment of T1D, but also highlights that additional optimisation may be required to achieve its full potential.



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Expansion of CD11b+Ly-6C+ myeloid-derived suppressor cells (MDSCs) driven by galectin-9 attenuates CVB3-induced myocarditis

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Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Yingying Zhang, Mengying Zhang, Xueqin Li, Zongsheng Tang, Ling He, Kun Lv
Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b+Ly-6C+ myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b+Ly-6C+ MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C+ MDSCs, but not Ly6G+ cells, expressed Arg-1 and NOS2, and suppressed CD4+ T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine. Furthermore, Ly6C+ MDSCs co-expressed higher levels of F4/80, Tim-3, and IL-4Rα, and had the plasticity to up-regulate NOS2 or Arg-1 in response to IFN-γ or IL-4 treatment. The present results indicate that galectin-9 expands CD11b+Ly-6C+ MDSCs to ameliorate CVB3-induced myocarditis.



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IL-12 and IL-23 modulate plasticity of FoxP3+ regulatory T cells in human Leprosy

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Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Mohd Tarique, Chaman Saini, Raza Ali Naqvi, Neena Khanna, Alpana Sharma, D.N. Rao
Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host's immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host by producing IL-10 and TGF-β cytokines. In leprosy, plasticity of Tregs remain unstudied. This is the first study describing the conversion of Tregs into Th1-like and Th17-like cells using in vitro cytokine therapy in leprosy patients. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA), rIL-12 and rIL-23 for 48h. Expression of FoxP3 in CD4+CD25+ Tregs, intracellular cytokines IFN-γ, TGF-β, IL-10 and IL-17 in Tregs cells were evaluated by flow cytometry (FACS) after stimulation. rIL-12 treatment increases the levels of pStat4 in Tregs and IFN-γ production. In the presence of rIL-23, pStat3+ and IL-17A+ cells increase. rIL-12 and r—IL-23 treatment downregulated the FoxP3 expression, IL-10 and TGF-β production by Tregs and enhances the expression of co-stimulatory molecules (CD80, CD86). In conclusion rIL-12 converts Tregs into IFN-γ producing cells through STAT-4 signaling while rIL-23 converts Tregs into IL-17 producing cells through STAT-3 signaling in leprosy patients. This study may helpful to provide a new avenue to overcome the immunosuprression in leprosy patients using in vitro cytokine.



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The protection effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione, a curcumin analogue, against operative liver injury in rats

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Xiaowei Chi, Dan Yu, Peijing Li, Qianfeng Lu, Wenjiao Jiang, Kun Hao
The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2–4.8mmol/kg) was administrated 10min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8mmol/kg) administrated 10min before ischemia and N-acetylcysteine (NAC) (4.8mmol/kg) administrated 10min before reperfusion were included for comparative studies. The plasma liver enzyme activities, histopathological indices and markers of lipid peroxide were determined to evaluate the hepatic protection effects. Effects of DDD on succinate dehydrogenase (SDH) activity were also investigated. DDD showed dose-dependent hepatocyte protections when administrated 10min before reperfusion stages in hepatic IRI rats. DDD showed almost equivalent hepatoprotective effects when administrated 10min before ischemia phase demonstrating that DDD acted on the reperfusion stages selectively against the hepatic IRI, instead of ischemia phase. NAC was not effective against hepatic IRI when treated 10min before reperfusion because of the higher pKa of NAC. In additional, DDD had no effect on the SDH both in hepatic IRI rats and in mitochondria. In conclusion, DDD had dose-dependent hepatocyte protections in the reperfusion stages in hepatic IRI rats, while the observed hepatocyte protections of DDD did not involve SDH activities. β-Diketone structures of DDD were crucial for the hepatocyte protections. The abilities of DDD to clear up the unsaturated aldehydes related with the enolate nucleophilicity and the pKa. DDD might be a promising candidate to treat hepatic IRI.

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Characterization, pharmacokinetics and tissue distribution of chlorogenic acid-loaded self-microemulsifying drug delivery system

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Li Chen, Chang-shun Liu, Qing-zhen Chen, Sen Wang, Yong-ai Xiong, Jing Jing, Jia-jia Lv
The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Chlorogenic acid (CA), an important bioactive compound from Lonicerae Japonicae Flos with poor permeability. SMEDDS was prepared and characterized by self-emulsifying rate, morphological observation, droplet size determination, stability, in vitro release, in vivo bioavailability and tissue distribution experiments. Results shown that the SMEDDS of CA has a high self-emulsifying rate (>98%) in the dissolution media, and its microemulsion exhibits small droplet size (16.37nm) and good stability. In vitro release test showed a complete release of CA from SMEDDS in 480min. After oral administration in mice, significantly enhanced bioavailability of CA was achieved through SMEDDS (249.4% relative to the CA suspension). Interestingly, SMEDDS significantly changed the tissue distribution of CA and showed a better targeting property to the kidney (2.79 of the relative intake efficiency). It is suggested that SMEDDS improves the oral bioavailability of CA may mainly through increasing its absorption and slowing the metabolism of absorbed CA via changing its distribution from the liver to the kidney. In conclusion, it is indicated that SMEDDS is a promising carrier for the oral delivery of CA.

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Engineering hot-melt extruded solid dispersion for controlled release of hydrophilic drugs

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Shuli Zhang, Xuan Meng, Zheng Wang, Aiping Fan, Guocheng Wang, Yanjun Zhao, Yu Tang
It is often challenging to precisely manipulate the release behavior of hydrophilic drugs that is believed to be crucial for a satisfactory therapeutic outcome. The aim of this work was to regulate the dissolution of hydrophilic drug from hot-melt extruded solid dispersion via rational screening of the pore-forming agents. Venlafaxine hydrochloride and Compritol® 888 ATO was selected as the model drug and carrier excipient, respectively. Hydrophilic polyethylene glycol (PEG 6000) and polyvinylpyrolidone (PVP K30) were chosen as the transient pore-forming agents. The X-ray diffraction and thermal analysis showed that both drug and carrier existed in the crystalline form. Both types of polymers could generate pores upon dissolution test and the drug release rate was proportionally correlated to the pore-forming agent content. The mathematical modelling showed that the Ritger-Peppas model gave the best fit to the release curves, which demonstrates a diffusion-dominant release mechanism. The scanning electron microscopy and mercury intrusion porosimetry analysis proved that PVP K30 could generate large pores with low porosity, but PEG 6000 produced smaller pores with relatively high porosity. The in vivo pharmacokinetics study in rat revealed that solid dispersions containing either PEG 6000 or PVP K30 (both at 2.5%, w/w) exhibited an elevated bioavailability compared to the commercial product, Effexor® XR. The current work implied that rational screening of transient pore-forming polymer in solid dispersion could be a robust approach for controlling hydrophilic drug release.

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Environmental and ecological risk of heavy metals in the marine sediment from Dakhla Bay, Morocco

Abstract

Heavy metal assessment in Dakhla Bay (Atlantic coast) was carried out using different environmental and ecological indices. Heavy metal concentrations were measured using ICP–AES and were compared with consensus-based sediment quality guidelines. The distribution of heavy metal concentrations varies for the three groups: (i) lead distribution is dominated by its associations with copper and chromium. These elements have the same source, most probably related to anthropogenic activities. (ii) Nickel, zinc and cobalt are associated with aluminium and iron indicating their terrigenous origin (natural content), and (iii) cadmium concentration is related to upwelling currents. This paper systematically studied the distributions and pollution levels of heavy metals in sediment in the coastal areas in Dakhla Bay, which is of scientific significance, to discuss the changing rules and the affecting factors of the harmful heavy metals and can be adopted for reference to other coastal areas.



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