Graphene-based masterbatch obtained via modified polyvinyl alcohol liquid-shear exfoliation and its application in enhanced polymer composites

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Douglas A. Simon, Eveline Bischoff, Giovanna G. Buonocore, Pierfrancesco Cerruti, Maria G. Raucci, Hesheng Xia, Henri S. Schrekker, Marino Lavorgna, Luigi Ambrosio, Raquel S. Mauler
A simple and inexpensive method for the production of graphene-based masterbatch via polymer-assisted shear exfoliation of graphite in water was comprehensively investigated. In detail, a modified polyvinyl alcohol (mPVOH) characterized by surface energy comparable with that of graphene was used as surfactant for the production of graphene-like particles. The proposed approach allowed a yield in graphene-like particles higher than that obtained by using common surfactants, along with a narrower size distribution. A mPVOH-masterbatch containing 4.38wt% of graphene-like particles was produced by removing the aqueous solvent from a dispersion and directly used for production of polymer nanocomposites by melt processing. Films prepared by blending the masterbatch with polyvinyl alcohol in order to have a graphene-like particles content equal to 0.3wt% showed a 78% reduction in water permeability and a 48% increase in storage modulus as compared with pristine polymers. Improved barrier properties were also observed for polylactic acid (PLA) and low-density polyethylene (LDPE)-based composite films, whereas an increment of about 520% in the storage modulus was observed for the composite obtained with PLA. The obtained results are very relevant and the proposed process will open up a new pathway for using graphene-based masterbatch in the packaging industry.

Graphical abstract

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In situ observation on temperature dependence of martensitic transformation and plastic deformation in superelastic NiTi shape memory alloy

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Yao Xiao, Pan Zeng, Liping Lei, Yanzhi Zhang
In situ digital image correlation (DIC) and in situ X-ray diffraction (XRD) are applied to investigate the effect of temperature on martensitic transformation and plastic deformation in superelastic NiTi shape memory alloy. Via in situ DIC, two well-known deformation modes of NiTi are identified at various temperatures: (A) localized forward and reverse transformations with little residual strain (<1%); (B) localized forward transformation and homogenous reverse transformation with considerable residual strain (>1%). As temperature increases from 25°C to 120°C, the mechanical response of NiTi gradually transits from Type A to Type B. We verify that plastic strain accumulates concurrently as the traverse of the front of localized deformation band. Via in situ XRD observation, we conclude that it is material plasticity rather than retained martensite that plays a dominant role in the irreversibility of NiTi. The experimental results provide both macroscopic and lattice level scenarios to understand the temperature dependence of complicated thermomechanical coupling and plasticity in superelastic NiTi.

Graphical abstract

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Structure and properties of silkworm cocoon (Bombyx mori) treated by hot pressing

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Tao Wang, Lanlan Chen, Lingmei Du, Tingting Shen, Fei Li, Lan Huang, Zhi Li, Dayang Wu
The silkworm cocoon has outstanding mechanical properties due to the specific composite structure. However, the individual cocoon is small and irregular in shape which dramatically hinders its application in artificial composites. Here, rectangular pieces of silkworm cocoons were cut and combined into large sheets by means of hot pressing. The structure and properties of compressed cocoon pieces were investigated. The thickness and porosity of pieces are significantly decreased at the high pressure, besides silk fibers are more deformed and bonded at high temperature cause of sericin's softening and fusion. Tensile strength and modulus are remarkably increased compared to those of the raw cocoon, and so do the interlayer bonding. The stable thermal property of the compressed cocoons demonstrates that compression at a high temperature has little harm to cocoons. Therefore, hot pressing is a practical way to build artificial cocoon composites for engineering applications.

Graphical abstract

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Effect of hatch length on the development of microstructure, texture and residual stresses in selective laser melted superalloy Inconel 718

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Naresh Nadammal, Sandra Cabeza, Tatiana Mishurova, Tobias Thiede, Arne Kromm, Christoph Seyfert, Lena Farahbod, Christoph Haberland, Judith Ann Schneider, Pedro Dolabella Portella, Giovanni Bruno
In the present study, samples fabricated by varying the deposition hatch length during selective laser melting of nickel based superalloy Inconel 718 were investigated. Microstructure and texture of these samples was characterized using scanning electron microscopy, combined with electron back-scattered diffraction, and residual stress assessment, using neutron diffraction method. Textured columnar grains oriented along the sample building direction were observed in the shorter hatch length processed sample. A ten-fold increase in the hatch length reduced the texture intensity by a factor of two attributed to the formation of finer grains in the longer hatch length sample. Larger gradients of transverse residual stress in the longer hatch length sample were also observed. Along the build direction, compressive stresses in the shorter hatch length and negligible stresses for the longer hatch length specimen were observed. Changes to the temperature gradient (G) in response to the hatch length variation, influenced the G to growth rate (R) ratio and the product G×R, in agreement with the microstructures and textures formed. For the residual stress development, geometry of the part also played an important role. In summary, tailored isotropy could be induced in Inconel 718 by a careful selection of parameters during selective laser melting.

Graphical abstract

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Factors associated with routine childhood vaccine uptake and reasons for non-vaccination in India: 1998–2008

Publication date: Available online 24 August 2017
Source:Vaccine
Author(s): Mark Rohit Francis, Hanna Nohynek, Heidi Larson, Vinohar Balraj, Venkata Raghava Mohan, Gagandeep Kang, J. Pekka Nuorti
BackgroundDespite almost three decades of the Universal Immunization Program in India, a little more than half the children aged 12–23months receive the full schedule of routine vaccinations. We examined socio-demographic factors associated with partial-vaccination and non-vaccination and the reasons for non-vaccination among Indian children during 1998 and 2008.MethodsData from three consecutive, nationally-representative, District Level Household and Facility Surveys (1998–99, 2002–04 and 2007–08) were pooled. Multinomial logistic regression was used to identify individual and household level socio-demographic variables associated with the child's vaccination status. The mother's reported reasons for non-vaccination were analyzed qualitatively, adapting from a previously published framework.ResultsThe pooled dataset contained information on 178,473 children 12–23months of age; 53%, 32% and 15% were fully vaccinated, partially vaccinated and unvaccinated respectively. Compared with the 1998–1999 survey, children in the 2007–2008 survey were less likely to be unvaccinated (Adjusted Prevalence Odds Ratio (aPOR): 0.92, 95%CI=0.86–0.98) but more likely to be partially vaccinated (aPOR: 1.58, 95%CI=1.52–1.65). Vaccination status was inversely associated with female gender, Muslim religion, lower caste, urban residence and maternal characteristics such as lower educational attainment, non-institutional delivery, fewer antenatal care visits and non-receipt of maternal tetanus vaccination. The mother's reported reasons for non-vaccination indicated gaps in awareness, acceptance and affordability (financial and non-financial costs) related to routine vaccinations.ConclusionsPersisting socio-demographic disparities related to partial-vaccination and non-vaccination were associated with important childhood, maternal and household characteristics. Further research investigating the causal pathways through which maternal and social characteristics influence decision-making for childhood vaccinations is needed to improve uptake of routine vaccination in India. Also, efforts to increase uptake should address parental fears related to vaccination to improve trust in government health services as part of ongoing social mobilization and communication strategies.



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Vaccine exemptions and the kindergarten vaccination coverage gap

Publication date: Available online 24 August 2017
Source:Vaccine
Author(s): Philip J. Smith, Jana Shaw, Ranee Seither, Adriana Lopez, Holly A. Hill, Mike Underwood, Cynthia Knighton, Zhen Zhao, Megha Shah Ravanam, Stacie Greby, Walter A. Orenstein
BackgroundVaccination requirements for kindergarten entry vary by state, but all states require 2 doses of measles containing vaccine (MCV) at kindergarten entry.ObjectiveTo assess (i) national MCV vaccination coverage for children who had attended kindergarten; (ii) the extent to which undervaccination after kindergarten entry is attributable to parents' requests for an exemption; (iii) the extent to which undervaccinated children had missed opportunities to be administered missing vaccine doses among children whose parent did not request an exemption; and (iv) the vaccination coverage gap between the "highest achievable" MCV coverage and actual MCV coverage among children who had attended kindergarten.MethodsA national survey of 1465 parents of 5–7year-old children was conducted during October 2013 through March 2014. Vaccination coverage estimates are based provider-reported vaccination histories. Children have a "missed opportunity" for MCV if they were not up-to-date and if there were dates on which other vaccines were administered but not MCV. The "highest achievable" MCV vaccination coverage rate is 100% minus the sum of the percentages of (i) undervaccinated children with parents who requested an exemption; and (ii) undervaccinated children with parents who did not request an exemption and whose vaccination statuses were assessed during a kindergarten grace period or period when they were provisionally enrolled in kindergarten.ResultsAmong all children undervaccinated for MCV, 2.7% were attributable to having a parent who requested an exemption. Among children who were undervaccinated for MCV and whose parent did not request an exemption, 41.6% had a missed opportunity for MCV. The highest achievable MCV coverage was 98.6%, actual MCV coverage was 90.9%, and the kindergarten vaccination gap was 7.7%.ConclusionVaccination coverage may be increased by schools fully implementing state kindergarten vaccination laws, and by providers assessing children's vaccination status at every clinic visit, and administering missed vaccine doses.



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Evaluation of the RumiWatchSystem for measuring grazing behaviour of cows

Publication date: Available online 24 August 2017
Source:Journal of Neuroscience Methods
Author(s): J. Werner, L. Leso, C. Umstatter, J. Niederhauser, E. Kennedy, A. Geoghegan, L. Shalloo, M. Schick, B. O'Brien
Feeding behaviour is an important parameter of animal performance, health and welfare, as well as reflecting levels and quality of feed available. Previously, sensors were only used for measuring animal feeding behaviour in indoor housing systems. However, sensors such as the RumiWatchSystem can also monitor such behaviour continuously in pasture-based environments. Therefore, the aim of this study was to validate the RumiWatchSystem to record cow activity and feeding behaviour in a pasture-based system. The RumiWatchSystem was evaluated against visual observation across two different experiments. The time duration per hour at grazing, rumination, walking, standing and lying recorded by the RumiWatchSystem was compared to the visual observation data in Experiment 1. Concordance Correlation Coefficient (CCC) values of CCC=0.96 for grazing, CCC=0.99 for rumination, CCC=1.00 for standing and lying and CCC=0.92 for walking were obtained. The number of grazing and rumination bouts within one hour were also analysed resulting in Cohen's Kappa (κ)=0.62 and κ=0.86 for grazing and rumination bouts, respectively. Experiment 2 focused on the validation of grazing bites and rumination chews. The accordance between visual observation and automated measurement by the RumiWatchSystem was high with CCC=0.78 and CCC=0.94 for grazing bites and rumination chews, respectively. These results indicate that the RumiWatchSystem is a reliable sensor technology for observing cow activity and feeding behaviour in a pasture based milk production system, and may be used for research purposes in a grazing environment.



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Effects of a combination of 3,4-methylenedioxymeth amphetamine and caffeine on real time stimulated dopamine release in the rat striatum: studies using fast cyclic voltammetry

Publication date: Available online 24 August 2017
Source:Journal of Neuroscience Methods
Author(s): J.J. O'Connor, K.M. O'Boyle, J.P. Lowry
It is well documented that caffeine exacerbates the hyperthermia associated with acute exposure to 3,4-methylenedioxymethamphetamine (MDMA) in rats. Previous reports have also indicated that MDMA-related enhancement of dopamine release is exacerbated in the presence of caffeine. In the present study we have examined whether the effects of MDMA on real-time stimulated dopamine release in the absence of uptake inhibition are accentuated in the presence of caffeine. Isolated striatal slices from adult male Wistar rats were treated acutely with MDMA, caffeine, or a combination, and their effects on single and 5pulse stimulated dopamine release monitored using the technique of fast cyclic voltammetry. Caffeine at 10 or 100μM had no significant effect on single pulse stimulated dopamine release. However 100μM caffeine caused a significant peak increase in 5pulse stimulated dopamine release. Both 1 and 30μM MDMA gave rise to a significant increase in both single and 5-pulse dopamine release and reuptake. A combination of 100μM caffeine and 1 or 30μM MDMA did not significantly enhance the effects of MDMA on single or 5pulse dopamine release and reuptake when compared to that applied alone. Utilizing single action potential dependent dopamine release, these results do not demonstrate a caffeine-enhanced MDMA-induced dopamine release.



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Development of a head-mounted wireless microstimulator for deep brain stimulation in rats

Publication date: Available online 24 August 2017
Source:Journal of Neuroscience Methods
Author(s): Felix Fluri, Thomas Mützel, Michael K. Schuhmanna, Miloš Krstić, Heinz Endres, Jens Volkmann
BackgroundCommercial neurostimulators for clinical use are effective in patients; however they are too large and prohibitively expensive for preclinical studies. Thus, there is an urgent need of a small inexpensive and wireless microstimulator which is fully programmable in frequency, pulse width and amplitude for rodent experiments.New methodsRats were subjected to a photothrombotic stroke of the right sensorimotor cortex and a microelectrode was implanted in the right mesencephalic locomotor region. The microstimulator was connected with the head plug of the rat. Three different stimulation frequencies were applied and different stimulating amplitudes were chosen. Under these conditions, gait velocity and locomotor behavior of six rats were examined on a beam.ResultsThe head-mounted microstimulator allowed freedom in all motor activities performed spontaneously by the tested rats. Increasing either the frequency or the stimulating amplitude increased gait velocity and ameliorated locomotor behavior after stroke.Comparison with existing methodsOther devices for DBS in rodents must be implanted under the skin or worn in an animal jacket on the back by the tested rat. Some available systems require even a tethering of the tested animal via a cable to an external stimulation system, which limits the freedom of movement.ConclusionHere, we present a freely programmable microstimulator including DBS-typical stimulating parameters. The lightweight device is connected by a simple plug to the head allowing full freedom of movement and exchange of batteries for long-term experiments. The design of this stimulator is suitable for sophisticated behavior tests requiring balance and skilled walking.



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An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate

Publication date: Available online 24 August 2017
Source:Cell Host & Microbe
Author(s): Luisella Spiga, Maria G. Winter, Tatiane Furtado de Carvalho, Wenhan Zhu, Elizabeth R. Hughes, Caroline C. Gillis, Cassie L. Behrendt, Jiwoong Kim, Daniela Chessa, Helene L. Andrews-Polymenis, Daniel P. Beiting, Renato L. Santos, Lora V. Hooper, Sebastian E. Winter
The mucosal inflammatory response induced by Salmonella serovar Typhimurium creates a favorable niche for this gut pathogen. Conventional wisdom holds that S. Typhimurium undergoes an incomplete tricarboxylic acid (TCA) cycle in the anaerobic mammalian gut. One change during S. Typhimurium-induced inflammation is the production of oxidized compounds by infiltrating neutrophils. We show that inflammation-derived electron acceptors induce a complete, oxidative TCA cycle in S. Typhimurium, allowing the bacteria to compete with the microbiota for colonization. A complete TCA cycle facilitates utilization of the microbiota-derived fermentation product succinate as a carbon source. S. Typhimurium succinate utilization genes contribute to efficient colonization in conventionally raised mice, but provide no growth advantage in germ-free mice. Mono-association of gnotobiotic mice with Bacteroides, a major succinate producer, restores succinate utilization in S. Typhimurium. Thus, oxidative central metabolism enables S. Typhimurium to utilize a variety of carbon sources, including microbiota-derived succinate.

Graphical abstract

Teaser

Spiga et al. show that during colonization of the intestinal lumen, the enteric pathogen S. Typhimurium performs a complete TCA cycle. This oxidative central metabolism enables S. Typhimurium to utilize the microbiota-derived fermentation product succinate as a nutrient and to compete with the microbiota for colonization of the intestinal tract.


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A Brucella Type IV Effector Targets the COG Tethering Complex to Remodel Host Secretory Traffic and Promote Intracellular Replication

Publication date: Available online 24 August 2017
Source:Cell Host & Microbe
Author(s): Cheryl N. Miller, Erin P. Smith, Jennifer A. Cundiff, Leigh A. Knodler, Jessica Bailey Blackburn, Vladimir Lupashin, Jean Celli
Many intracellular pathogens exploit host secretory trafficking to support their intracellular cycle, but knowledge of these pathogenic processes is limited. The bacterium Brucella abortus uses a type IV secretion system (VirB T4SS) to generate a replication-permissive Brucella-containing vacuole (rBCV) derived from the host ER, a process that requires host early secretory trafficking. Here we show that the VirB T4SS effector BspB contributes to rBCV biogenesis and Brucella replication by interacting with the conserved oligomeric Golgi (COG) tethering complex, a major coordinator of Golgi vesicular trafficking, thus remodeling Golgi membrane traffic and redirecting Golgi-derived vesicles to the BCV. Altogether, these findings demonstrate that Brucella modulates COG-dependent trafficking via delivery of a T4SS effector to promote rBCV biogenesis and intracellular proliferation, providing mechanistic insight into how bacterial exploitation of host secretory functions promotes pathogenesis.

Graphical abstract

Teaser

How bacterial pathogens exploit host secretory functions to achieve their intracellular cycle remains poorly understood. Miller et al. show here that Brucella abortus delivers into macrophages a type IV-secretion effector that remodels Golgi-associated membrane traffic to promote biogenesis of the Brucella replicative vacuole and bacterial proliferation.


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Corrigendum

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Clinical Snippets

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Striatal synapses, circuits, and Parkinson's disease

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Shenyu Zhai, Asami Tanimura, Steven M Graves, Weixing Shen, D James Surmeier
The striatum is a hub in the basal ganglia circuitry controlling goal directed actions and habits. The loss of its dopaminergic (DAergic) innervation in Parkinson's disease (PD) disrupts the ability of the two principal striatal projection systems to respond appropriately to cortical and thalamic signals, resulting in the hypokinetic features of the disease. New tools to study brain circuitry have led to significant advances in our understanding of striatal circuits and how they adapt in PD models. This short review summarizes some of these recent studies and the gaps that remain to be filled.



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Parsing learning in networks using brain–machine interfaces

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Amy L Orsborn, Bijan Pesaran
Brain–machine interfaces (BMIs) define new ways to interact with our environment and hold great promise for clinical therapies. Motor BMIs, for instance, re-route neural activity to control movements of a new effector and could restore movement to people with paralysis. Increasing experience shows that interfacing with the brain inevitably changes the brain. BMIs engage and depend on a wide array of innate learning mechanisms to produce meaningful behavior. BMIs precisely define the information streams into and out of the brain, but engage wide-spread learning. We take a network perspective and review existing observations of learning in motor BMIs to show that BMIs engage multiple learning mechanisms distributed across neural networks. Recent studies demonstrate the advantages of BMI for parsing this learning and its underlying neural mechanisms. BMIs therefore provide a powerful tool for studying the neural mechanisms of learning that highlights the critical role of learning in engineered neural therapies.



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Mechanically dynamic PDMS substrates to investigate changing cell environments

Publication date: November 2017
Source:Biomaterials, Volume 145
Author(s): Yi-Cheun Yeh, Elise A. Corbin, Steven R. Caliari, Liu Ouyang, Sebastián L. Vega, Rachel Truitt, Lin Han, Kenneth B. Margulies, Jason A. Burdick
Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ∼1300 to 1900 μm² and from ∼2700 to 4600 μm² for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ∼2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM.



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Mitteilungen der DGKFO

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Multiscale design and synthesis of biomimetic gradient protein/biosilica composites for interfacial tissue engineering

Publication date: November 2017
Source:Biomaterials, Volume 145
Author(s): Jin Guo, Chunmei Li, Shengjie Ling, Wenwen Huang, Ying Chen, David L. Kaplan
Continuous gradients present at tissue interfaces such as osteochondral systems, reflect complex tissue functions and involve changes in extracellular matrix compositions, cell types and mechanical properties. New and versatile biomaterial strategies are needed to create suitable biomimetic engineered grafts for interfacial tissue engineering. Silk protein-based composites, coupled with selective peptides with mineralization domains, were utilized to mimic the soft-to-hard transition in osteochondral interfaces. The gradient composites supported tunable mineralization and mechanical properties corresponding to the spatial concentration gradient of the mineralization domains (R5 peptide). The composite system exhibited continuous transitions in terms of composition, structure and mechanical properties, as well as cytocompatibility and biodegradability. The gradient silicified silk/R5 composites promoted and regulated osteogenic differentiation of human mesenchymal stem cells in an osteoinductive environment in vitro. The cells differentiated along the composites in a manner consistent with the R5-gradient profile. This novel biomimetic gradient biomaterial design offers a useful approach to meet a broad range of needs in regenerative medicine.



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Deriving vascular smooth muscle cells from mesenchymal stromal cells: Evolving differentiation strategies and current understanding of their mechanisms

Publication date: November 2017
Source:Biomaterials, Volume 145
Author(s): Xiaoqing Zhang, Michelle P. Bendeck, Craig A. Simmons, J. Paul Santerre
Vascular smooth muscle cells (VSMCs) play essential roles in regulating blood vessel form and function. Regeneration of functional vascular smooth muscle tissue to repair vascular diseases is an area of intense research in tissue engineering and regenerative medicine. For functional vascular smooth muscle tissue regeneration to become a practical therapy over the next decade, the field will need to have access to VSMC sources that are effective, robust and safe. While pluripotent stem cells hold good future promise to this end, more immediate translation is expected to come from approaches that generate functional VSMCs from adult sources of multipotent adipose-derived and bone marrow-derived mesenchymal stromal cells (ASCs and BMSCs). The research to this end is extensive and is dominated by studies relating to classical biochemical signalling molecules used to induce differentiation of ASCs and BMSCs. However, prolonged use of the biochemical induction factors is costly and can cause potential endotoxin contamination in the culture. Over recent years several non-traditional differentiation approaches have been devised to mimic defined aspects of the native micro-environment in which VSMCs reside to contribute to the differentiation of VSMC-like cells from ASCs and BMSCs. In this review, the promises and limitations of several non-traditional culture approaches (e.g., co-culture, biomechanical, and biomaterial stimuli) targeting VSMC differentiation are discussed. The extensive crosstalk between the underlying signalling cascades are delineated and put into a translational context. It is expected that this review will not only provide significant insight into VSMC differentiation strategies for vascular smooth muscle tissue engineering applications, but will also highlight the fundamental importance of engineering the cellular microenvironment on multiple scales (with consideration of different combinatorial pathways) in order to direct cell differentiation fate and obtain cells of a desired and stable phenotype. These strategies may ultimately be applied to different sources of stem cells in the future for a range of biomaterial and tissue engineering disciplines.



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The stigma of clean dieting and orthorexia nervosa

Abstract

Background

Although the stigma of eating disorders such as anorexia has been well established, little is known about the social consequences of "clean dieting" and orthorexia nervosa. In two studies, we examined the social stigma of clean dieting and orthorexia.

Method

In Study 1, participants read a vignette describing a woman following a "clean" diet, a woman with anorexia, or a control target (minimal information about the individual). In Study 2, participants read a vignette describing a woman with orthorexia, a woman displaying identical orthorexic behaviors but without the orthorexia label, a woman with anorexia, or a control target. Participants then rated the target individual on a range of measures assessing stereotypes, emotions, and behavioral intentions toward the target.

Results

Study 1 found that the clean-dieting target was evaluated more negatively than the control target on some dimensions, but less negatively than the target with anorexia nervosa. Study 2 found that evaluations of the targets with orthorexia nervosa were more negative than evaluations of a control target, but did not differ from evaluations of the target with anorexia nervosa. Perceptions of the target's control over her behavior were associated with more positive evaluations (Studies 1 and 2), whereas perceptions of blame and responsibility for the condition were associated with more negative evaluations (Study 2).

Conclusions

Overall, these findings highlight the potential negative social consequences of clean dieting and orthorexia nervosa, and point to perceptions of control and blame as potential mechanisms underlying the stigma of these conditions.

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A New Charter on Professionalism and Health Care Organizations.

Author: Andresen, May-Lynn DNP, RN; Mason, Diana J. PhD, RN, FAAN

Page: 11

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Critical Thinking During Time-Out Protocols.

Author: Lott, Charles

Page: 13

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Critical Thinking During Time-Out Protocols.

Author: S., Sharon via ajnoffthecharts.com

Page: 13

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Helping Pregnant Smokers Quit.

Author: G., Daniel via ajnoffthecharts.com

Page: 13

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Natural Disasters and Resilience Training.

Author: Gasparrelli, Sharilyn M. RN, CNOR

Page: 13

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Keeping Assessment Skills Sharp.

Author: Valenzuela, Joshua

Page: 13

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Gun Violence and Children.

Author: Sofer, Dalia

Page: 14

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How Long Should Routine Health Screening Continue?.

Author: Stockwell, Serena

Page: 15

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NewsCAP: Survey outlines the current characteristics of CNSs.

Author:

Page: 15

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Two Studies Suggest Fewer Opioids Could Be Prescribed After Cesarean Sections.

Author: Potera, Carol

Page: 16

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NewsCAP: New app may streamline breast milk management in the NICU.

Author:

Page: 16

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Trends in U.S. Health Care.

Author:

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NewsCAP: Even moderate alcohol use affects cognitive function.

Author:

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NewsCAP: Support services for older adults, caregivers, and those with disabilities have improved, but progress is too slow.

Author:

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NewsCAP: One of every 200 people in Yemen suspected of having cholera.

Author:

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Will Rural Community Hospitals Survive?.

Author: Nelson, Roxanne

Page: 18-19

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AJN On the Cover.

Author: Szulecki, Diane Editor

Page: 20

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AJN On the Web.

Author:

Page: 20

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Delayed Onset Cranial Nerve Palsies After Endovascular Coil Embolization of Direct Carotid-Cavernous Fistulas.

Background: Late recurrence of visual symptoms associated with carotid-cavernous fistula (CCF), including diplopia, is uncommon and raises concern for new or recurrent fistula formation. Methods: We report 2 patients with traumatic CCFs, where cranial nerve paresis resolved after endovascular CCF treatment only to reappear years later. Results: No evidence of recurrent or new fistula formation was found. Both were treated successfully with strabismus surgery. Conclusions: Although the cause of delayed onset diplopia after successful treatment is still unknown, theories include late compression of cranial nerves within the cavernous sinus due to coil mass that can cause chronic ischemia, delayed inflammation due to a thrombophilic nidus created by the coil mass, or injury to the cranial nerves that manifests later due to decompensated strabismus. (C) 2017 by North American Neuro-Ophthalmology Society

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Gorham-Stout Disease Presenting as Acute Unilateral Proptosis.

Gorham-Stout disease (GSD) is a rare angiomatous disorder characterized by osteolysis. We report the case of a 66-year-old woman who developed sudden left eye proptosis and facial pain. Neuroimaging demonstrated a destructive mass involving the roof and lateral wall of the left orbit with adjacent abnormal orbital soft tissue. An initial biopsy of the soft tissue was nondiagnostic; however, transcranial biopsy of the orbital roof revealed an intraosseous cavernous angioma, with infiltration of orbital fat by angiomatous tissue. Despite resection of the orbital roof and lateral wall, the orbital lesion continued to expand, leading to signs of a compressive optic neuropathy. The patient then reported severe back pain, prompting imaging that demonstrated disseminated bony involvement of the axial skeleton, eventually leading to the diagnosis of GSD. The patient was treated with a bisphosphonate and a vascular endothelial growth factor inhibitor with stabilization of disease. (C) 2017 by North American Neuro-Ophthalmology Society

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Co-Trained Convolutional Neural Networks for Automated Detection of Prostate Cancer in Multi-parametric MRI

Publication date: Available online 24 August 2017
Source:Medical Image Analysis
Author(s): Xin Yang, Chaoyue Liu, Zhiwei Wang, Jun Yang, Hung Le Min, Liang Wang, Kwang-Ting (Tim) Cheng
Multi-parameter magnetic resonance imaging (mp-MRI) is increasingly popular for prostate cancer (PCa) detection and diagnosis. However, interpreting mp-MRI data which typically contains multiple unregistered 3D sequences, e.g. apparent diffusion coefficient (ADC) and T2-weighted (T2w) images, is time-consuming and demands special expertise, limiting its usage for large-scale PCa screening. Therefore, solutions to computer-aided detection of PCa in mp-MRI images are highly desirable. Most recent advances in automated methods for PCa detection employ a handcrafted feature based two-stage classification flow, i.e. voxel-level classification followed by a region-level classification. This work presents an automated PCa detection system which can concurrently identify the presence of PCa in an image and localize lesions based on deep convolutional neural network (CNN) features and a single-stage SVM classifier. Specifically, the developed co-trained CNNs consist of two parallel convolutional networks for ADC and T2w images respectively. Each network is trained using images of a single modality in a weakly-supervised manner by providing a set of prostate images with image-level labels indicating only the presence of PCa without priors of lesions' locations. Discriminative visual patterns of lesions can be learned effectively from clutters of prostate and surrounding tissues. A cancer response map with each pixel indicating the likelihood to be cancerous is explicitly generated at the last convolutional layer of the network for each modality. A new back-propagated error E is defined to enforce both optimized classification results and consistent cancer response maps for different modalities, which help capture highly representative PCa-relevant features during the CNN feature learning process. The CNN features of each modality are concatenated and fed into a SVM classifier. For images which are classified to contain cancers, non-maximum suppression and adaptive thresholding are applied to the corresponding cancer response maps for PCa foci localization. Evaluation based on 160 patient data with 12-core systematic TRUS-guided prostate biopsy as the reference standard demonstrates that our system achieves a sensitivity of 0.46, 0.92 and 0.97 at 0.1, 1 and 10 false positives per normal/benign patient which is significantly superior to two state-of-the-art CNN-based methods (Oquab et al., 2015; Zhou et al., 2015) and 6-core systematic prostate biopsies.

Graphical abstract

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Impact of microRNAs on ischemic stroke: From pre- to post-disease

Publication date: Available online 24 August 2017
Source:Progress in Neurobiology
Author(s): Guangwen Li, Kahlilia C. Morris-Blanco, Mary S. Lopez, Tuo Yang, Haiping Zhao, Raghu Vemuganti, Yumin Luo
Stroke is the number one cause of neurological dysfunction in adults and has a heavy socioeconomic burden worldwide. The etiological origins of ischemic stroke and resulting pathological processes are mediated by a multifaceted cascade of molecular mechanisms that are in part modulated by posttranscriptional activity. Accumulating evidence has revealed a role for microRNAs (miRNAs) as essential mediators of posttranscriptional gene silencing in both the physiology of brain development and pathology of ischemic stroke. In this review, we compile miRNAs that have been reported to regulate various stroke risk factors and pre-disease mechanisms, including hypertension, atherosclerosis, and diabetes, followed by an in-depth analysis of miRNAs in ischemic stroke pathogenesis, such as excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis and neurogenesis. Since promoting or suppressing expression of miRNAs by specific pharmaceutical and non-pharmaceutical therapies may be beneficial to post-stroke recovery, we also highlight the potential therapeutic value of miRNAs in clinical settings.



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Use and Perceptions of Electronic Cigarettes Among Caregivers of Infants and Children with Bronchopulmonary Dysplasia

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Use and Perceptions of Electronic Cigarettes Among Caregivers of Infants and Children with Bronchopulmonary Dysplasia

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2xxx1sA

Mitteilungen der DGKFO

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Contrast Enhanced Spectral Mammography: A Review

Publication date: Available online 24 August 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Bhavika K. Patel, M.B.I. Lobbes, John Lewin
Contrast-enhanced spectral mammography (CESM) provides low-energy 2D mammographic images comparable to standard digital mammography and a post-contrast recombined image to assess tumor neovascularity similar to MRI. The utilization of CESM in the United States is currently low but could increase rapidly given many potential indications for clinical use. This article discusses historical background and literature review of indications and diagnostic accuracy of CESM to date. CESM is a growing technique for breast cancer detection and diagnosis that has levels of sensitivity and specificity on par with contrast-enhanced breast MRI. Because of its similar performance and ease of implementation, CESM is being adopted for multiple indications previously reserved for MRI, such as problem-solving, disease-extent in newly diagnosed patients and evaluating the treatment response of neoadjuvant chemotherapy.



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Thoracolithiasis – CT findings of intrapleural loose bodies

Publication date: Available online 24 August 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Gabriela Gayer
Thoracoliths are rare benign intrapleural loose bodies, often containing calcification, that are mobile in the pleural cavity. The presence of these intrapleural nodules is referred to as thoracolithiasis. The exact etiology of thoracoliths is unknown, but they presumably result from a prior episode of mediastinal (epipericardial) fat necrosis. Thoracoliths are usually asymptomatic and incidentally encountered on CT.However, they sometimes pose diagnostic challenges, as a thoracolith may be located within a pleural fissure, and is then indistinguishable from a pulmonary nodule. In addition, migration and rotation of thoracoliths within the pleural space observed on serial CT studies has been reported to raise concern that these might be neoplastic lesions, leading to their surgical removal. Awareness of this benign condition is important in order to avoid unnecessary invasive procedures.



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Optimizing success and avoiding mishaps in the most difficult image guided breast biopsies

Publication date: Available online 24 August 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Sughra Raza, Sona A. Chikarmane, Eva C. Gombos, Dianne Georgian-Smith, Elisabeth P. Frost
Breast cancer is an increasing challenge in developed and limited resource areas of the world. Early detection of breast cancer offers the best chance for optimal care and best outcomes. A critical step in early detection is to obtain efficient and accurate tissue diagnoses. While image-guided core needle breast biopsies are usually straightforward for experienced breast imagers, there are some not uncommon scenarios which present particular challenges. In this review article we will discuss these difficult situations and offer our tried and true methods to ensure safe and successful biopsies, while using stereotactic, ultrasound, and MRI guidance.



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Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

Publication date: Available online 24 August 2017
Source:Journal of Proteomics
Author(s): Simon Vyse, Frank McCarthy, Malgorzata Broncel, Angela Paul, Jocelyn P. Wong, Amandeep Bhamra, Paul H. Huang
Acquired drug resistance impacts the majority of patients being treated with tyrosine kinase inhibitors (TKIs) and remains a key challenge in modern anti-cancer therapy. The lack of clinically effective therapies to overcome resistance represents an unmet need. Understanding the signalling that drives drug resistance will facilitate the development of new salvage therapies to treat patients with secondary TKI resistance. In this study, we utilise mass spectrometry to characterise the global phosphoproteomic alterations that accompany the acquisition of resistance to two FDA-approved TKIs, pazopanib and dasatinib, in the A204 rhabdoid tumour cell line. Our analysis finds that only 6% and 9.7% of the quantified phosphoproteome is altered upon the acquisition of pazopanib and dasatinib resistance respectively. Pazopanib resistant cells display elevated phosphorylation in cytoskeletal regulatory pathways while dasatinib resistant cells show an upregulation of the insulin receptor/IGF-1R signalling pathway. Drug response profiling rediscovers several previously reported vulnerabilities associated with pazopanib and dasatinib resistance and identifies a new dependency to the second generation HSP90 inhibitor NVP-AUY-922. This study provides a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance.SignificancePazopanib and dasatinib are tyrosine kinase inhibitors (TKIs) approved for the treatment of multiple cancer types. Patients who are treated with these drugs are prone to the development of drug resistance and consequently tumour relapse. Here we use quantitative phosphoproteomics to characterise the signalling pathways which are enriched in cells that have acquired resistance to these two drugs. Furthermore, targeted drug screens were used to identify salvage therapies capable of overcoming pazopanib and dasatinib resistance. This data advances our understanding of the mechanisms of TKI resistance and highlights candidate targets for cancer therapy.



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The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms

Publication date: Available online 24 August 2017
Source:Journal of Proteomics
Author(s): Stuart Ainsworth, Daniel Petras, Mikael Engmark, Roderich D. Süssmuth, Gareth Whiteley, Laura-Oana Albulescu, Taline D. Kazandjian, Simon C. Wagstaff, Paul Rowley, Wolfgang Wüster, Pieter C. Dorrestein, Ana Silvia Arias, José M. Gutiérrez, Robert A. Harrison, Nicholas R. Casewell, Juan J. Calvete
Mambas (genus Dendroaspis) are among the most feared of the medically important elapid snakes found in sub-Saharan Africa, but many facets of their biology, including the diversity of venom composition, remain relatively understudied. Here, we present a reconstruction of mamba phylogeny, alongside genus-wide venom gland transcriptomic and high-resolution top-down venomic analyses. Whereas the green mambas, D. viridis, D. angusticeps, D. j. jamesoni and D. j. kaimosae, express 3FTx-predominant venoms, black mamba (D. polylepis) venom is dominated by dendrotoxins I and K. The divergent terrestrial ecology of D. polylepis compared to the arboreal niche occupied by all other mambas makes it plausible that this major difference in venom composition is due to dietary variation. The pattern of intrageneric venom variability across Dendroaspis represented a valuable opportunity to investigate, in a genus-wide context, the variant toxicity of the venom, and the degree of paraspecific cross-reactivity between antivenoms and mamba venoms. To this end, the immunological profiles of the five mamba venoms were assessed against a panel of commercial antivenoms generated for the sub-Saharan Africa market. This study provides a genus-wide overview of which available antivenoms may be more efficacious in neutralising human envenomings caused by mambas, irrespective of the species responsible. The information gathered in this study lays the foundations for rationalising the notably different potency and pharmacological profiles of Dendroaspis venoms at locus resolution. This understanding will allow selection and design of toxin immunogens with a view to generating a safer and more efficacious pan-specific antivenom against any mamba envenomation.Biological significanceThe mambas (genus Dendroaspis) comprise five especially notorious medically important venomous snakes endemic to sub-Saharan Africa. Their highly potent venoms comprise a high diversity of pharmacologically active peptides, including extremely rapid-acting neurotoxins. Previous studies on mamba venoms have focused on the biochemical and pharmacological characterisation of their most relevant toxins to rationalize the common neurological and neuromuscular symptoms of envenomings caused by these species, but there has been little work on overall venom composition or comparisons between them. Only very recently an overview of the composition of the venom of two Dendroaspis species, D. angusticeps and D. polylepis, has been unveiled through venomics approaches. Here we present the first genus-wide transcriptomic-proteomic analysis of mamba venom composition. The transcriptomic analyses described in this paper have contributed 29 (D. polylepis), 23 (D. angusticeps), 40 (D. viridis), 25 (D. j. jamesoni) and 21 (D. j. kaimosae), novel full-length toxin sequences to the non-redundant Dendroaspis sequence database. The mamba genus-wide venomic analysis demonstrated that major D. polylepis venom components are Kunitz-fold family toxins. This feature is unique in relation to the relatively conserved three-finger toxin (3FTx)-dominated venom compositions of the green mambas. Venom variation was interpreted in the context of dietary variation due to the divergent terrestrial ecology of D. polylepis compared to the arboreal niche occupied by all other mambas. Additionally, the degree of cross-reactivity conservation of mamba venoms was assessed by antivenomics against a panel of commercial antivenoms generated for the sub-Saharan Africa market. This study provides a genus-wide overview to infer which available antivenoms may be capable of neutralising human envenomings caused by mambas, irrespective of the species responsible. The information gathered in this study lays the foundations for rationalising the pharmacological profiles of mamba venoms at locus resolution. This understanding will contribute to the generation of a safer and more efficacious pan-Dendroaspis therapeutic antivenom against any mamba envenomation.

Graphical abstract

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Structural identification of N-linked carbohydrates using the GUcal application: A tutorial

Publication date: Available online 24 August 2017
Source:Journal of Proteomics
Author(s): Gabor Jarvas, Marton Szigeti, Andras Guttman
In recent years, analytical glycomics gained a significant role due to the rapidly increasing number of glycoproteins introduced as biopharmaceuticals. One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. Individual glycan structures corresponding to the separated peaks in an electropherogram are identified according to their glucose unit (GU) values by mining the built in database. This tutorial introduces the practical use of the GUcal application, a recently developed glycoinformatics tool, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the recently published triple internal standard method. Furthermore, a worked example demonstrates the way glycan structural elucidation of human immunoglobulin G is processed with the help of this simple and rapid GU value calculation application.SignificanceBiopharmaceuticals have seen something of tremendous development in recent years, which governs the parallel blooming of analytical glycomics. One of the frequently used methods for the analysis of complex carbohydrates is capillary electrophoresis with laser induced fluorescent detection (CE-LIF). CE-LIF is a high resolution separation technique with excellent sensitivity capable of discriminating between closely related positional and linkage carbohydrate isomers. While CE instrumentation is well developed, the related bioinformatics tools are lagging behind. According to our best knowledge, this is the first tutorial paper on the recently disseminated GUcal application, which automatically calculates GU values for all sample components of interest in an electropherogram using either the bracketing standard approach or the new triple internal standard method. On the top the step-by-step instruction how to use the application, the paper includes a worked example demonstrates the way glycan structure elucidation of human immunoglobulin G is processed with the help of the simple and rapid GU value calculation of this new application. After very short training period, the software can be used readily for cutting-edge glycomics of exploratory research or high-throughput routine analysis.

Graphical abstract

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Rooted in the Community: Assessing the Reintegration Impacts of Agriculture on Rural Veterans

Publication date: Available online 24 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Karen Besterman-Dahan, Margeaux Chavez, Eni Njoh
ObjectiveTo assess the impact of a Veteran-oriented community agricultural initiative (CAI) on transitioning rural Veterans.DesignConvergent mixed-method program evaluation.SettingA Veteran-oriented farm-to-market CAI in rural Washington State.ParticipantsVeterans who were members of the CAI.Main Outcome MeasuresHealth, well-being, and reintegration were assessed by self-reported data from interview, demographic survey, validated health quality of life measure (Veterans RAND-12 -VR-12), validated reintegration measure (Military to Civilian Questionnaire -M2C-Q), and general satisfaction survey.ResultsVeteran participants were primarily Caucasian (88.4%, n=38) and male (74.4%, n=32) and most had a service-connected disability rating (58.2%, n=25). Qualitative and quantitative data revealed that the veterans participating in this CAI experienced health and reintegration benefits. Results on the M2C-Q, VR-12, and the satisfaction survey suggest that participating in this CAI contributed to improved mental, physical, and emotional health and vocational skills, community connectedness, and interpersonal communication. Qualitative interviews supported quantitative findings and revealed that participating in the CAI provided Veterans with a sense of satisfaction, belonging, and helped decrease the stigma surrounding their Veteran status.ConclusionsVeterans who participate in this CAI reported general improvements in physical and mental health, including improvements in sleep, nutrition, exercise, and decreases in anxiety, pain, depression and medication and substance use, all known factors which impact Veteran reintegration.



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Low-dose-rate prostate brachytherapy: 4–8 week postimplant prostate-specific antigen a novel predictor of biochemical failure-free survival

Publication date: Available online 24 August 2017
Source:Brachytherapy
Author(s): Cameron M. Callaghan, Lin Wang, Abhishek Alluri, Andrew Lauve, Cynthia Boyer, William Russell
PurposeThe purpose of this study was to determine the relationship between patient, disease, and treatment variables and biochemical failure-free survival (bFFS) following low-dose-rate prostate brachytherapy (LDR-BT).Methods and MaterialsData from 624 consecutive patients who received LDR-BT for localized prostate cancer between 2002 and 2012 at a single institution were collected for various patient, disease, and treatment characteristics including a 4–8 week postimplant PSA (4–8wkPSA). Subgroup analysis was stratified by risk category and treatment regimen. Analysis was performed using Kaplan–Meier survival curves, Cox proportional hazard ratios (HRs), and receiver-operator characteristic curves.ResultsA total of 624 consecutive patients were included with followup time of 4.0 ± 3.1 years. Predictors of bFFS included PSA nadir and 4–8wkPSA (HR = 2.48, p = 0.000 and HR = 1.24, p = 0.000, respectively) for total population. Diabetes mellitus (p = 0.026), chronic obstructive pulmonary disease (p = 0.000), alcohol use (p = 0.024), and age (p = 0.002) were predictors for specific subgroups. Receiver-operator characteristic curves 4–8wkPSA were found to be significant (p = 0.036).Conclusion4–8wkPSA is a novel predictor of bFFS for patients receiving LDR-BT across several risk categories and treatment regimens with potential clinical utility as a prognostic indicator. Certain comorbidities and exposure histories also demonstrated significant relationships with bFFS including chronic obstructive pulmonary disease, diabetes mellitus, age, alcohol history, proton pump inhibitor use, PSA nadir, and PSA density.



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Clinical implementation of a novel Double-Balloon single-entry breast brachytherapy applicator

Publication date: Available online 24 August 2017
Source:Brachytherapy
Author(s): Bethany M. Anderson, Charles R. Wallace, Anna-Maria A. De Costa, Rupak K. Das
PurposeThe purpose of the study was to describe the clinical utilization of a novel Double-Balloon applicator for accelerated partial breast irradiation (APBI).Methods and MaterialsThe Double-Balloon single-entry breast applicator contains a single central treatment catheter, as well as four peripheral catheters that can be differentially loaded to customize radiation dose coverage. An inner balloon is filled with up to 7–30 cm³ of saline to increase separation between the peripheral catheters, and an outer balloon is filled with up to 37–115 cm³ of saline to displace breast tissue from the peripheral catheters. Treatment planning objectives include coverage of the breast planning target volume to a minimum of V90 > 90%, limiting dose heterogeneity such that V200 < 10 cm³ and V150 < 50 cm³, and limiting maximum dose to skin (<100% of prescription dose) and ribs (<145% of prescription dose).ResultsHigh-dose-rate APBI was delivered to 11 women using this device (34 Gy in 10 twice daily fractions). The mean V90 was 98.2% (range 94.2–99.4%). The mean skin Dmax with the Double-Balloon applicator was 83.3% (range 75.6–99.5%). The mean breast V200 was 5.8 cm³ (range 2.3–10.2 cm³), and the mean breast V150 was 32.9 cm³ (range 25.0–41.7 cm³). Pretreatment quality assurance was performed using CT prior to each morning fraction and ultrasound prior to each afternoon fraction.ConclusionsThe Double-Balloon applicator can be easily introduced into a previously existing brachytherapy program. APBI plans created with this applicator achieve excellent planning target volume coverage, while limiting skin dose and maintaining breast V200 < 10 cm³.



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Performance, emission, and combustion characteristics of twin-cylinder common rail diesel engine fuelled with butanol-diesel blends

Abstract

Nitrogen oxides and smoke are the substantial emissions for the diesel engines. Fuels comprising high-level oxygen content can have low smoke emission due to better oxidation of soot. The objective of the paper is to assess the potential to employ oxygenated fuel, i.e., n-butanol and its blends with the neat diesel from 0 to 30% by volume. The experimental and computational fluid dynamic (CFD) simulation is carried out to estimate the performance, combustion, and exhaust emission characteristics of n-butanol-diesel blends for various injection timings (9°, 12°, 15°, and 18°) using modern twin-cylinder, four-stroke, common rail direct injection (CRDI) engine. Experimental results reveal the increase in brake thermal efficiency (BTE) by ~ 4.5, 6, and 8% for butanol-diesel blends of 10% (Bu10), 20% (Bu20), and 30% (Bu30), respectively, compared to neat diesel (Bu0). Maximum BTE for Bu0 is 38.4%, which is obtained at 12° BTDC; however, for Bu10, Bu20 and Bu30 are 40.19, 40.9, and 41.7%, which are obtained at 15° BTDC, respectively. Higher flame speed of n-butanol-diesel blends burn a large amount of fuel in the premixed phase, which improves the combustion as well as emission characteristics. CFD and experimental results are compared and validated for all fuel blends for in-cylinder pressure and nitrogen oxides (NO_x), and found to be in good agreement. Both experimental and simulation results witnessed in reduction of smoke opacity, NO_x, and carbon monoxide emissions with the increasing n-butanol percentage in diesel fuel.

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Mortality and its Causes in a German Cohort with Diabetes Mellitus Type 1 after 20 Years of Follow-Up: The JEVIN Trial

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-113452

Background The JEVIN trial started as a cross-sectional study in 1989/90 in Jena. After a follow-up of more than 20 years, the mortality incidence of JEVIN participants with type 1 diabetes was surveyed. Methods 103 (78.6%) of the 131 JEVIN patients participating at baseline could be examined. 38 persons (36.9%) had deceased. All JEVIN survey data and routine examinations documented in the electronic patient record EMIL® of surviving and deceased participants were used for analyses. We compared the data of the surviving with the deceased participants (follow-up time: 2,166 person-years). Results The incidence rate of death was 1.75/100 person-years. Median observation time for all patients was 23.1 years (range 0.61–26.6 years). Mean age at death was 58.5 years (34.2–78.4 years), and diabetes duration 35 years (3.5–68.5 years). Most frequent causes of death were: cardiovascular diseases (48.2%, n=13) and infections (25.9%, n=7). There were no differences in age (p=0.302), diabetes duration (p=0.371), BMI (p=0.535), blood pressure (p=0.622/0.820), gender (p=0.566), and smoking status (p=0.709) between surviving and deceased persons. The mean HbA1c of the last year before death or last visit was higher in the deceased than surviving persons (7.5% vs. 7.0%; p=0.010). 57.4% of the surviving and 87.0% of the deceased participants had nephropathy (p=0.012), 79.7% vs. 89.7% retinopathy (p=0.241) and 61.4% vs. 63.3% neuropathy (p=0.860), but only nephropathy was significantly associated with increased mortality risk (HR=4.208, CI:1.226-14.440; HR=2.360, CI:0.696-8.004; HR=0.944, CI:0.436-2.043). Conclusions In the JEVIN population with diabetes mellitus type 1 only, diabetic nephropathy was associated with higher mortality risk.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Characterization of FaDu-R, a radioresistant head and neck cancer cell line, and cancer stem cells

Publication date: Available online 24 August 2017
Source:Auris Nasus Larynx
Author(s): Kwang-Jae Cho, Eun-Ji Park, Min-Sik Kim, Young-Hoon Joo
ObjectivesThe aim of this study was to evaluate the impact of CSC on insensitivity to radiotherapy in HNSCC.MethodsA radioresistant cell line, FaDu-R, was established using fractionated ionizing radiation. Cells with high and low CD44/ALDH activity were isolated.ResultsFaDu-R cells demonstrated significantly increased cell viability after radiation exposure compared with parental cells. CD44^high/ALDH^high FaDu-R cells demonstrated significantly faster wound closure (p<0.05) and more efficient invasion (p<0.05) compared to the CD44^high/ALDH^high FaDu cells or the CD44^low/ALDH^low FaDu-R cells. There was a significant difference in tumor volume between the CD44^high/ALDH^high FaDu-R cells and the CD44^high/ALDH^high FaDu cells (p<0.05) as well as the CD44^low/ALDH^low FaDu-R cells (p<0.05).ConclusionCancer stem cells (CSC) were associated with invasion and tumorigenesis in a radioresistant head and neck squamous cell carcinoma (HNSCC) cell line. This concept might help to improve the understanding of these mechanisms and to develop drugs that can overcome radioresistance during radiotherapy.



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Risk factors for the occurrence of epistaxis: Prospective study

Publication date: Available online 24 August 2017
Source:Auris Nasus Larynx
Author(s): Filipa Camacho Côrte, Tiago Orfao, Cláudia Camila Dias, Carla Pinto Moura, Margarida Santos
ObjectiveAnalyse and compare the characteristics of patients with epistaxis admitted to the otolaryngology emergency department with those provided by a control group. Establish a model to identify epistaxis predictive factors.MethodsProspective analysis of 283 consecutive adults, admitted to the otolaryngology emergency department of a tertiary referral centre between 25 January and 25 February 2014. Comparison of gender, age, co-morbidities, usual medication, history of epistaxis or nasal trauma, presence of septal deviation and blood pressure value on admission, between the elements that were admitted to the emergency due to epistaxis (group 1) and a group composed of patients with other symptoms (group 2). Intergroup variations were analyzed using t student and chi-square tests. Multivariate logistic regression and a receiver operating characteristic curve were used to establish a predictive model and test its suitability.ResultsMale gender (OR=2.57, 95% CI 1.1–6.0, p=0.029), older age (OR=1.03, 95% CI 1.0–1.1, p=0.002), existence of peripheral vascular disease (OR=13.47, 95% CI 1.9–95.3, p=0.009), cardiovascular disease (OR=3.91, 95% CI 1.6–9.7, p=0.003) and previous history of epistaxis (OR=5.53, 95% CI 2.5–12.1, p<0.001) were predictors of epistaxis when adjusted for the presence of elevated blood pressure, history of hypertension, cerebrovascular disease and chronic use of anticoagulants or antiplatelet drugs. The model revealed a good applicability (area under the curve of 0.852).ConclusionsThe only predictive factors of admission to the emergency department due to epistaxis were male gender, older age, peripheral vascular disease, cardiovascular disease and history of epistaxis.



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A case of ectopic salivary gland of the larynx

Publication date: Available online 24 August 2017
Source:Auris Nasus Larynx
Author(s): Shori Tajima, Kouichi Yamauchi, Ryuzaburo Higo, Katsuhisa Ikeda
A 46-year-old man presented with sore throat. Laryngoscopic findings revealed a smooth yellow mass occupying the anterior portion of the false vocal fold on the left side. The authors performed biopsy under general anesthesia. The histopathological diagnosis was ectopic salivary gland. Because salivary glands are usually not found under the false vocal fold mucosa, ectopic salivary gland of the larynx was diagnosed.It is necessary to consider the possibility of ectopic salivary gland for mass lesions if swelling of the provisional vocal cord is found.



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Characterization of FaDu-R, a radioresistant head and neck cancer cell line, and cancer stem cells

The aim of this study was to evaluate the impact of CSC on insensitivity to radiotherapy in HNSCC.

http://ift.tt/2xhDqc4

Characterization of FaDu-R, a radioresistant head and neck cancer cell line, and cancer stem cells

The aim of this study was to evaluate the impact of CSC on insensitivity to radiotherapy in HNSCC.

http://ift.tt/2xhDqc4

Automated anesthesia delivery systems in cardiac surgical patients with left ventricular dysfunction: All systems go?

The interest in the use of automated drug infusion systems to deliver anesthesia has grown amongst both clinicians and researchers since their inception decades ago. Presently, two major types of automated anesthesia delivery systems exist, both of which have been used predominantly to deliver intravenous medications as part of a general anesthetic.

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Idiopathic Rem Sleep Behavior Disorder In The Elderly Spanish Community: A Primary Care Center Study With A Two-Stage Design Using Video-Polysomnography

To examine the presence and characteristics of idiopathic REM sleep behavior disorder (IRBD) in a representative Caucasian sample from the elderly community of Lleida, Spain, attending primary care centers.

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Response to “GHB concentration in breast milk of narcoleptic women treated with sodium oxybate. How important it is to be careful when interpreting values.” (Letter to the Editor by Busardò PB and Pichini S)

We thank Drs. Busardò and Pichini for their letter and points regarding our recent manuscript entitled "GHB levels in breast milk of women with narcolepsy with cataplexy treated with sodium oxybate". We agree and acknowledge, within the manuscript, that the data collected by ours and others' laboratories should be corroborated by larger prospective studies with appropriate controls. In the absence of sufficient clinical trial data, however, we submit that small studies such as these can be helpful to physicians and patients in making decisions regarding medications during the perinatal period.

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Use of sialendoscopy as an aid to identify a large retained foreign body

Christopher J. Britt, MD; David Hyman, MD; Gregory K. Hartig, MD

Abstract

We describe the novel use of sialendoscopy in a 51-year-old man to identify a large and long-standing foreign body (wood) within the facial soft tissues that had eluded detection on previous imaging and surgical exploration. The identification of this foreign body was elusive on both computed tomography and magnetic resonance imaging, illustrating the limitations of imaging in identifying vegetable matter within soft tissues.

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A clinicopathologic and epidemiologic study of chronic white lesions in the oral mucosa

Sampurna Ghosh, MS; Sudipta Pal, MS; Soumya Ghatak, MS; Somnath Saha, MS; Surajit Biswas, MD; Prabha Srivastava, MD

Abstract

Invasive oral squamous cell carcinoma is often preceded by the presence of clinically identifiable premalignant changes of the oral mucosa, including white lesions. We conducted a cross-sectional, observational study to assess the clinicopathologic and epidemiologic aspects of chronic oral mucosal white lesions to determine the necessity of early biopsy in these cases. Our study population was made up of 77 patients-50 males and 27 females, aged 15 to 70 years (mean: 42.9)-who presented with white lesions persisting for at least 4 weeks. All but 3 patients underwent a biopsy; the 3 exceptions were diagnosed with smear-proven candidiasis. Patients with moderate or severe dysplasia underwent an excision biopsy. The buccal mucosa was the single most common site of white lesions, occurring in 15 patients (19.5%), although 21 patients (27.3%) exhibited a diffuse involvement of the oral mucosa. Of the 77 patients, 59 (76.6%) had concerning findings: premalignant lesions in 45 patients (58.4%) and malignant lesions in 14 (18.2%). Also, dysplasia was seen in 8 patients (10.4%), all of whom had premalignant lesions. Tobacco chewing (p = 0.008) and betel quid chewing (p = 0.029) were significantly associated with the development of premalignant and malignant lesions; a longer duration of tobacco chewing (≥10 yr) was significantly associated with a higher risk of malignant but not premalignant lesions (p = 0.031). Finally, illiteracy was a significant risk factor for premalignant and malignant lesions (p = 0.03). Our findings support the necessity of biopsy in every case. Early detection of oral carcinoma by biopsy of all oral white lesions would not only prevent patients from undergoing disfiguring surgery and chemoradiation, but it also would increase the 5-year survival rate.

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Nasal cavity tumefactive fibroinflammatory lesion mimicking recurrent mucoepidermoid carcinoma

Daniel Thomas Ginat, MD, MS; Elizabeth Blair, MD

The diagnostic imaging features of tumefactive fibroinflammatory lesions can mimic those of neoplasms.

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Cornelia de Lange syndrome: What every otolaryngologist should know

Michael J. Eliason, MD, USN, LCDR; Jonathan M. Melzer, MD, USN, LCDR; Thomas Q. Gallagher, DO, USN, CDR

Abstract

Cornelia de Lange Syndrome (CdLS) can be expressed in multiple organ systems requiring a variety of specialists, including pediatric otolaryngology. We present the case of a 20-month-old boy with CdLS actively managed by an aerodigestive team consisting of pediatric otolaryngology, pediatric pulmonology, pediatric gastroenterology, with support staff from audiology, speech, and nutrition. His presentation included mixed hearing loss, dysphagia, microaspiration, gastroesophageal reflux, and failure to thrive. We submit this challenging case of CdLS with a review of the literature to focus specific attention on the otolaryngic manifestations of the syndrome and to discuss the benefits of a multidisciplinary approach to these unique patients.

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An incidental thyroid nodule

John P. Flynn, MD; Peter A. Morawiecki, MD; Marco A. Ayala, MD

Preoperative diagnosis of intrathyroidal parathyroid adenomas is essential to determining correct surgical management

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Use and Perceptions of Electronic Cigarettes Among Caregivers of Infants and Children with Bronchopulmonary Dysplasia

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Comparison of clinical outcomes using a Piezosurgery device vs. a conventional osteotome for lateral osteotomy in rhinoplasty

Bulent Koc, MD; Eltaf Ayca Ozbal Koc, MD; Selim Erbek, MD

Abstract

Our aim for this study was to evaluate and compare the clinical outcomes in patients who underwent lateral osteotomy with a Piezosurgery device or a conventional osteotome in open-technique rhinoplasty. This cohort trial involved 65 patients (36 women and 29 men; average age: 23.6 ± 5.71 yr) who underwent surgery between May 2015 and January 2016. Piezosurgery was used for lateral osteotomy in 32 patients, whereas 33 patients underwent conventional external osteotomy. These 2 groups were compared for duration of surgery, perioperative bleeding, postoperative edema, ecchymosis, pain, and patient satisfaction on the first and seventh postoperative days. The Piezosurgery group revealed significantly more favorable outcomes in terms of edema, ecchymosis, and hemorrhage on the first day postoperatively (p < 0.001 for all). Similarly, edema (p = 0.005) and ecchymosis (p < 0.001) on the seventh postoperative day also were better in the Piezosurgery group. Hemorrhage was similar in both groups on the seventh postoperative day (p = 0.67). The Piezosurgery group not only experienced less pain on the first postoperative day (p < 0.001), but these patients also were more satisfied with their results on both the first and seventh postoperative days. Results of the present study imply that Piezosurgery may be a promising, safe, and effective method for lateral osteotomy, a critical step in rhinoplasty. The time interval necessary for the learning curve is counteracted by the comfort and satisfaction of both patients and surgeons.

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A clinicopathologic and epidemiologic study of chronic white lesions in the oral mucosa

Sampurna Ghosh, MS; Sudipta Pal, MS; Soumya Ghatak, MS; Somnath Saha, MS; Surajit Biswas, MD; Prabha Srivastava, MD

Abstract

Invasive oral squamous cell carcinoma is often preceded by the presence of clinically identifiable premalignant changes of the oral mucosa, including white lesions. We conducted a cross-sectional, observational study to assess the clinicopathologic and epidemiologic aspects of chronic oral mucosal white lesions to determine the necessity of early biopsy in these cases. Our study population was made up of 77 patients-50 males and 27 females, aged 15 to 70 years (mean: 42.9)-who presented with white lesions persisting for at least 4 weeks. All but 3 patients underwent a biopsy; the 3 exceptions were diagnosed with smear-proven candidiasis. Patients with moderate or severe dysplasia underwent an excision biopsy. The buccal mucosa was the single most common site of white lesions, occurring in 15 patients (19.5%), although 21 patients (27.3%) exhibited a diffuse involvement of the oral mucosa. Of the 77 patients, 59 (76.6%) had concerning findings: premalignant lesions in 45 patients (58.4%) and malignant lesions in 14 (18.2%). Also, dysplasia was seen in 8 patients (10.4%), all of whom had premalignant lesions. Tobacco chewing (p = 0.008) and betel quid chewing (p = 0.029) were significantly associated with the development of premalignant and malignant lesions; a longer duration of tobacco chewing (≥10 yr) was significantly associated with a higher risk of malignant but not premalignant lesions (p = 0.031). Finally, illiteracy was a significant risk factor for premalignant and malignant lesions (p = 0.03). Our findings support the necessity of biopsy in every case. Early detection of oral carcinoma by biopsy of all oral white lesions would not only prevent patients from undergoing disfiguring surgery and chemoradiation, but it also would increase the 5-year survival rate.

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Paresis podule on a paralyzed vocal fold

Karthik S. Shastri, MD; Aaron J. Jaworek, MD; Robert T. Sataloff, MD, DMA, FACS

Paresis podules are localized areas of Reinke edema that can develop on paretic or paralyzed vocal folds, or on the contralateral vocal fold.

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Cornelia de Lange syndrome: What every otolaryngologist should know

Michael J. Eliason, MD, USN, LCDR; Jonathan M. Melzer, MD, USN, LCDR; Thomas Q. Gallagher, DO, USN, CDR

Abstract

Cornelia de Lange Syndrome (CdLS) can be expressed in multiple organ systems requiring a variety of specialists, including pediatric otolaryngology. We present the case of a 20-month-old boy with CdLS actively managed by an aerodigestive team consisting of pediatric otolaryngology, pediatric pulmonology, pediatric gastroenterology, with support staff from audiology, speech, and nutrition. His presentation included mixed hearing loss, dysphagia, microaspiration, gastroesophageal reflux, and failure to thrive. We submit this challenging case of CdLS with a review of the literature to focus specific attention on the otolaryngic manifestations of the syndrome and to discuss the benefits of a multidisciplinary approach to these unique patients.

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Nasal cavity tumefactive fibroinflammatory lesion mimicking recurrent mucoepidermoid carcinoma

Daniel Thomas Ginat, MD, MS; Elizabeth Blair, MD

The diagnostic imaging features of tumefactive fibroinflammatory lesions can mimic those of neoplasms.

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Laryngeal Manual Therapies for Behavioral Dysphonia: A Systematic Review and Meta-analysis

The aim of this study was to review systematically the literature and to analyze the effectiveness of laryngeal manual therapy in addressing the overall severity of vocal deviation, the intensity of vocal and laryngeal symptoms, and musculoskeletal pain in adults with behavioral dysphonia.

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Internship Match and Entry Level Exam Performance of Undergraduate versus Graduate Level Didactic Students

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): B. Leonberg




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Table of Contents

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9





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Registered Dietitians Facilitate Diabetes Training and Care within a Patient Centered Medical Home Care Delivery Model

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): M. McClarney, M. Timmerman, G. Woscyna, C. Hanson




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Disclosure Page

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement





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What's New Online

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9





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Outstanding Dietetics Student Awards, 2017

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9





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Table of Contents

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement





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2017-2018 Officers List and Committee Members

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9





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Sports Dietetics: Impact Beyond Playing Fields

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9
Author(s): Donna S. Martin




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Acknowledgements

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement





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Increased Malnutrition Diagnosis and Reimbursement Indicates Success of Academy of Nutrition and Dietetics Nutrition Focused Physical Exam (NFPE) Hands-on Training Workshop

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): B. Mordarski, R. Hand, J. Wolff, A. Steiber




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Breastfeeding after Gestational Diabetes: GIS Analysis of Maternal-Infant Health Interventions

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): E. MacQuillan, A. Curtis




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Middle East Dietetics Needs Assessment: Identifying Opportunities for Future Collaborative Activities

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): E. Myers, R. Hakeem, N. Bdour, T. Kour, F. Atayata, S. Tashtoush, N. Cakir Bicer, S. Sakar, C. Erginbas, R. Kahill, M. Herrera, M. Boyd




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Back to Basics: All About MyPlate Food Groups

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9
Author(s): Sarah Chang, Kristin Koegel




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Prevalence of Food Insecurity among Hospitalized Patients

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): D. Sowa, C. Hartney, A. Asthana, S. Peterson




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Deepening the Commitment to Interprofessional Education and Practice: Updates from the Global Forum on Innovation in Health Professional Education and the Interprofessional Education Collaborative

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): K. Eliot, K. Kolasa




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Role of Nutrition Focused Physical Exam (NFPE) in the Identification of Malnutrition in Pediatric Patients

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): R. Pipkorn, C. Leon, J. Crouse, N. Fabus, M.B. Feuling, C. Karls, E. Polzin, A. Smith, M. Froh




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Carbohydrate Intake Estimates Do Not Differ by Nursing or Nutrition Discipline or by Two Methods of Evaluation in Acute Care Diabetic Patients at an Academic Medical Center

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): B. Atkinson, M. Perrigue, S. Singh, D. Cuddeback, S. Roesor-Loken, A. Lillie, L. Suhr, D. Corl, W. Brent




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State Dietetic Practice Group Gets Involved in State Regulation Revisions: Relevant, Vital and Never Dull

Publication date: September 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 9, Supplement
Author(s): P. Fatzinger McShane, J. Geer, J. Rowley




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Design and Synthesis of Benzoacridines as Estrogenic and Anti-Estrogenic Agents

Publication date: Available online 24 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kohei Torikai, Rintaro Koga, Xiaohui Liu, Kaoru Umehara, Tatsuya Kitano, Kenji Watanabe, Tohru Oishi, Hiroshi Noguchi, Yasuyuki Shimohigashi
Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential. Herein, we report the construction of a 12-arylbenzoacridine library via a diversity-oriented strategy that furnished non-toxic estrogenic and anti-estrogenic agents. Derivatives with a hydroxy group at the molecular edge exhibit potent binding affinity to the estrogen receptor α (ERα) and ERβ (IC50 < μM), while binding to the estrogen-related receptor γ (ERRγ), i.e., an orphan nuclear receptor on which estrogens often trigger unfavorable events, was not observed. These findings offer valuable insights into 12-arylbenzoacridines as a novel platform for the development of selective estrogen-receptor modulators (SERMs).

Graphical abstract

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Pyrrolizines: design, synthesis, anticancer evaluation and investigation of the potential mechanism of action

Publication date: Available online 24 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ahmed M. Gouda, Ahmed H. Abdelazeem, Hany A. Omar, Ashraf N. Abdalla, Mohammed A.S. Abourehab, Hamed I. Ali
A novel set of pyrrolizine-5-carboxamides has been synthesized and evaluated for their anticancer potential against human breast MCF-7, lung carcinoma A549 and hepatoma Hep3B cancer cell lines. Compound 10c was the most active against MCF-7 with IC50 value of 4.72 µM, while compound 12b was the most active against A549 and Hep3B cell lines. Moreover, kinases/COXs inhibition and apoptosis induction were suggested as potential molecular mechanisms for the anticancer activity of the novel pyrrolizines based on their structural features. The new compounds significantly inhibited COX-1 and COX-2 with IC50 values in the ranges of 5.78-11.96 µM and 0.1-0.78 µM, respectively with high COX-2 selectivity over COX-1. Interestingly, the most potent compound in MTT assay, compound 12b, exhibited high inhibitory activity against COX-2 with selectivity index (COX-1/COX-2) > 100. Meanwhile, compound 12b displayed weak to moderate inhibition of six kinases with inhibition% (7-20%) compared to imatinib (inhibition% = 1-38%). The results of cell cycle analysis, annexin V PI/FITC apoptosis assay and caspase-3/7 assay revealed that compound 12b has the ability to induce apoptosis. The docking results of compound 12b into the active sites of COXs, ALK1 and Aurora A indicated that it fits nicely inside their active sites. Overall, the current study highlighted the significant anticancer activity of the newly synthesized pyrrolizines with a potential multi-targeted mechanism which could serve as a base for future studies and further structural optimization into potential anticancer agents.

Graphical abstract

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β-Arrestin biased dopamine D2 receptor partial agonists: synthesis and pharmacological evaluation

Publication date: Available online 24 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Barbara Männel, Harald Hübner, Dorothée Möller, Peter Gmeiner
β-Arrestin biased G protein-coupled receptor ligands represent important molecular probes and may increase favorable drug action and safety as novel therapeutics. Starting from recently discovered hydroxy-substituted heterocyclic piperazine scaffolds, we have developed a series of dopamine D2 receptor ligands with a pyrazolo[1,5-a]pyridine as secondary pharmacophore that is functionalized in position 3 by a formyl or hydroxyiminomethyl substituent. The ligands, especially the benzoxazinone 9d, were found to display substantial β-arrestin-2 recruitment, while being nearly devoid of activity in a GTPγS binding assay. Investigating a new series of truncated analogs lacking a secondary pharmacophore, considerable β-arrestin-2 recruitment in the absence of G protein activation was found, when a 5-hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one was combined with an N-propyl-substituted 1,4-diazepane (15c). Although 15c displayed reduced potency compared to 9d, the dose-response curves indicate that a hydroxy-substituted heterocyclic primary pharmacophore is sufficient for the functionally selective activation of D2R.

Graphical abstract

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Microcystins: Synthesis and structure–activity relationship studies toward PP1 and PP2A

Publication date: Available online 24 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Miriam Fontanillo, Maja Köhn
Microcystins are highly toxic cyanotoxins responsible for plant, animal and human poisoning. Exposure to microcystins, mainly through drinkable water and contaminated food, is a current world health concern. Although it is quite challenging, the synthesis of these potent cyanotoxins, analogs and derivatives helps to detect them, to evaluate their toxicological properties, and to elucidate their binding mechanisms to their main targets Protein Phosphatase-1 (PP1) and -2A (PP2A). This review focuses on synthetic approaches to prepare microcystins and analogs and compiles structure–activity relationship (SAR) studies that describe the unique features of microcystins that make them so potent.

Graphical abstract

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Phenolic Glycolipid Facilitates Mycobacterial Escape from Microbicidal Tissue-Resident Macrophages

Publication date: Available online 24 August 2017
Source:Immunity
Author(s): C.J. Cambier, Seónadh M. O'Leary, Mary P. O'Sullivan, Joseph Keane, Lalita Ramakrishnan
Mycobacterium tuberculosis (Mtb) enters the host in aerosol droplets deposited in lung alveoli, where the bacteria first encounter lung-resident alveolar macrophages. We studied the earliest mycobacterium-macrophage interactions in the optically transparent zebrafish. First-responding resident macrophages phagocytosed and eradicated infecting mycobacteria, suggesting that to establish a successful infection, mycobacteria must escape out of the initially infected resident macrophage into growth-permissive monocytes. We defined a critical role for mycobacterial membrane phenolic glycolipid (PGL) in engineering this transition. PGL activated the STING cytosolic sensing pathway in resident macrophages, inducing the production of the chemokine CCL2, which in turn recruited circulating CCR2⁺ monocytes toward infection. Transient fusion of infected macrophages with CCR2⁺ monocytes enabled bacterial transfer and subsequent dissemination, and interrupting this transfer so as to prolong mycobacterial sojourn in resident macrophages promoted clearing of infection. Human alveolar macrophages produced CCL2 in a PGL-dependent fashion following infection, arguing for the potential of PGL-blocking interventions or PGL-targeting vaccine strategies in the prevention of tuberculosis.Video Abstract

Graphical abstract

Teaser

Cambier et al. find that activation of the STING pathway in lung-resident microbicidal macrophages by the mycobacterial surface lipid PGL enables bacterial escape by inducing the recruitment of mycobacterium-permissive monocytes via the CCL2-CCR2 chemokine axis. Their findings reveal a relocation strategy that enables mycobacterial dissemination, and argue for the potential of interventions targeting PGL in the prevention of tuberculosis.


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In Memoriam: Dr. Edmund Thile, former SLHS faculty member

Edmund Thile, Ph.D., CCC-SLP

Dr. Thile, age 85, passed away last week (August 2017) after a yearlong battle with leukemia.

Dr. Thile served on the faculty at San Diego State University from 1965 to 1998 as a Professor of Communicative Disorders, Clinical Director, Clinical Supervisor, and Project Director for numerous federally funded training grants. He was a great advocate for the students and started the diversity program in the school and the college with his Health Care Opportunities Program (HCOP) – a grant program to get minority students into health care professions.  In 1976, Dr. Thile started San Diego County Speech Pathology Services, Inc. (County Speech) serving San Diego County residents with speech, language, and communication difficulties. 

Services for Dr. Thile will be held on Friday 9/1/17 at 10:00 am at Mission Point (in south Mission Beach), 2600 Bayside Walk, San Diego, 92109.  There will be a gathering for everyone at his home following the service (2681 Ocean Front Walk) – it is walkable from the service as it's across the street.

http://ift.tt/2xgybJN