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

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

Graphical abstract

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

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



http://ift.tt/2GeBtlE

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

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



http://ift.tt/2Fy2RK5

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

Abstract

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

http://ift.tt/2p5sNH1

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

Abstract

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

http://ift.tt/2HpqR2J

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

Abstract

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

http://ift.tt/2GeQ00F

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

Abstract

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

http://ift.tt/2HmxjaG

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

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




http://ift.tt/2oWTZrm

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

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




http://ift.tt/2DiNC5I

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

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

Graphical abstract

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

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

Graphical abstract

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

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

Graphical abstract

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

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

Graphical abstract

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

Abstract

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

http://ift.tt/2IfRgkR

Evaluation of cationic polyacrylamide-based hybrid coagulation for the removal of dissolved organic nitrogen

Abstract

Dissolved organic nitrogen (DON) is an important component of aquatic environment of which amount impacts water quality. Thus, removal of DON has attracted wide attention. At present, it is difficult for common coagulation to remove DON from the aquatic environment. The cationic polymers can help to improve the removal efficiency of DON to some extent, but the underlying mechanism of the ascension is not clear. In order to grasp its removal behavior and further improve the removal efficiency of DON in the future, we evaluated the effect of a hybridized coagulant of polyacrylamide with iron-based coagulant on removal of aquatic DON. A higher floc growth rate (119.82 μm/min) and recovery factors (26.96) were found in the hybrid coagulation. The parameters affecting the DON and the dissolved organic carbon (DOC) included the molar ratio of Zn to Fe (n_Zn/n_Fe), CPAM content, and molar ratio of OH to Fe (n_OH/n_Fe): n_Zn/n_Fe had a larger influence in DON removal than CPAM content; CPAM had a larger influence in the DOC removal; n_OH/n_Fe played a moderate effect between CPAM and n_Zn/n_Fe. Mutual effect of hybrid coagulants indicated the colloidal species to be helpful in enhancing DOC and DON removal. Other parameters affecting coagulation performance included the pH: the estimated maximum DON removal efficiency occurred at pH 6, DOC removal efficiency at pH 8. The above results found in this study showed that DON removal was affected by the ingredient and the species composition of the hybrid coagulant, and the water environmental parameter. The enhanced efficiency of DON removal in the presence of CPAM was mainly attributed to the increased adsorption-bridging and sweep-floc.

http://ift.tt/2p4nK8U

Trace analysis of parabens preservatives in drinking water treatment sludge, treated, and mineral water samples

Abstract

Parabens have been widely used as antimicrobial agents, mainly in food products, pharmaceuticals, and cosmetics. Although they are known as safe preservatives, they also cause some harm to human health, which has been discussed lately. Therefore, the aim of this study was to evaluate the occurrence of nine parabens (including isomers) in mineral and drinking waters, besides in drinking water treatment sludge (DWTS) samples with determination by liquid chromatography tandem mass spectrometry (LC-MS/MS). Both methods solid phase extraction (SPE) and QuEChERS were validated. Calibration curves showed a correlation coefficient of 0.99 for all compounds. LOQ values ranged from 0.04 to 4 μg L⁻¹ in aqueous matrices and from 5 to 500 ng g⁻¹ in DWTS. Recoveries between 70 and 115% were reached with RSD below 20% for all compounds in SPE whereas recoveries between 62 and 119% were found with RSD below 20% for almost all compounds in QuEChERS. Matrix effect had low values (< 20%); it was only above 20% for methylparaben in the SPE and for pentylparaben in the QuEChERS. Using a quick and simple extraction procedures with SPE, QuEChERS, and LC-MS/MS analyses, these methods proved to be selective and sensitive. They were successfully applied to real samples (treated water, mineral water, and sludge), and methylparaben was detected at concentration levels below 0.242 μg L⁻¹ in mineral and treated water samples and 10 ng g⁻¹ in DWTS samples.

http://ift.tt/2IgBcPJ

A Genetically Selected Cyclic Peptide Inhibitor of BCL6 Homodimerization

Publication date: Available online 9 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Eliot L. Osher, Francisco Castillo, Nagarajan Elumalai, Michael J. Waring, Garry Pairaudeau, Ali Tavassoli
We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexpeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its homodimerization, and subsequent binding of the SMRT2 corepressor peptide.

Graphical abstract

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Design, synthesis and biological evaluation of novel spiro-pentacylamides as acetyl-CoA carboxylase inhibitors

Publication date: Available online 9 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Qiangqiang Wei, Liankuo Mei, Yifei Yang, Hui Ma, Hongyi Chen, Huibin Zhang, Jinpei Zhou
Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays an important role in the regulation of fatty acid oxidation. Therefore, ACC inhibition offers a promising option for intervention in nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2DM) and cancer. In this paper, a series of spiro-pentacylamide derivatives were synthesized and evaluated for their ACC1/2 inhibitory activities and anti-proliferation effects on A549, H1975, HCT116, SW620 and Caco-2 cell lines in vitro. Compound 6o displayed potent ACC1/2 inhibitory activity (ACC1 IC50 = 0.527 μM, ACC2 IC50 = 0.397 μM) and the most potent anti-proliferation activities against A549, H1975, HCT116, SW620 and Caco-2 cell lines, with IC50 values of 1.92 μM, 0.38 μM, 1.22 μM, 2.05 μM and 5.42 μM respectively. Further molecular docking studies revealed that compound 6o maintained hydrogen bonds between the two carbonyls and protein backbone NHs (Glu-B2026 and Gly-B1958). These results indicate that compound 6o is a promising ACC1/2 inhibitor for the potent treatment of cancer.

Graphical abstract

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Development of a microbioreactor for glycoconjugate synthesis

Publication date: Available online 9 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Katsuji Haneda, Takefumi Oishi, Hiroshi Kimura, Toshiyuki Inazu
A microbioreactor immobilized with a synthase-type mutant enzyme, Endo-M-N175Q (glycosynthase) of endo-β-N-acetylglucosaminidase derived from Mucor hiemalis (Endo-M), was constructed and used for glycoconjugate synthesis. The transglycosylation was performed with a reaction mixture containing an oxazoline derivative of sialo complex-type glycoside (SG), which was prepared from a sialo complex-type glycopeptide SGP derived from hen egg yolk, as a glycosyl donor and N-Fmoc-N-acetylglucosaminyl-L-asparagine [Fmoc-Asn(GlcNAc)-OH] as an acceptor. The reaction mixture was injected into a glycosynthase microbioreactor at a constant flow rate. Highly efficient and nearly stoichiometric transglycosylation occurred in the microbioreactor, and the transglycosylation product was eluted from the other end of the reactor. The glycosynthase microbioreactor was stable and could be used repeatedly for a long time.

Graphical abstract

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Synthesis and fungicidal activity of novel imidazole-based ketene dithioacetals

Publication date: Available online 9 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Stephane Jeanmart, Julien Gagnepain, Pulakesh Maity, Clemens Lamberth, Fredrik Cederbaum, Ramya Rajan, Olivier Jacob, Mathias Blum, Stephane Bieri
Novel imidazole-based ketene dithioacetals show impressive in planta activity against the economically important plant pathogens Alternaria solani, Botryotinia fuckeliana, Erysiphe necator and Zymoseptoria tritici. Especially derivatives of the topical antifungal lanoconazole, which bear an alkynyloxy or a heteroaryl group in the para-position of the phenyl ring, exhibit excellent control of the mentioned phytopathogens. These compounds inhibit 14α -demethylase in the sterol biosynthesis pathway of the fungi. Synthesis routes starting from either benzaldehydes or acetophenones as well as structure-activity relationships are discussed in detail.

Graphical abstract

http://ift.tt/2p0lxfv

Fine-tuning the physicochemical properties of peptide-based blood-brain barrier shuttles

Publication date: Available online 9 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Somaye Ghasemy, Júlia García-Pindado, Fatemeh Aboutalebi, Kianoush Dormiani, Meritxell Teixidó, Morteza Malakoutikhah
N-methylation is a powerful method to modify the physicochemical properties of peptides. We previously found that a fully N-methylated tetrapeptide, Ac-(N-MePhe)4-CONH2, was more lipophilic than its non-methylated analog Ac-(Phe)4-CONH2. In addition, the former crossed artificial and cell membranes while the latter did not. Here we sought to optimize the physicochemical properties of peptides and address how the number and position of N-methylated amino acids affect these properties. To this end, 15 analogs of Ac-(Phe)4-CONH2 were designed and synthesized in solid-phase. The solubility of the peptides in water and their lipophilicity, as measured by ultra performance liquid chromatography (UPLC) retention times, were determined. To study the permeability of the peptides, the Parallel Artificial Membrane Permeability Assay (PAMPA) was used as an in vitro model of the blood-brain barrier (BBB). Contrary to the parent peptide, the 15 analogs crossed the artificial membrane, thereby showing that N-methylation improved permeability. We also found that N-methylation enhanced lipophilicity but decreased the water solubility of peptides. Our results showed that both the number and position of N-methylated residues are important factors governing the physicochemical properties of peptides. There was no correlation between the number of N-methylated amide bonds and any of the properties measured. However, for the peptides consecutively N-methylated from the N-terminus to the C-terminus (p1, p5, p11, p12 and p16), lipophilicity correlated well with the number of N-methylated amide bonds and the permeability of the peptides. Moreover, the peptides were non-toxic to HEK293T cells, as determined by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay.

Graphical abstract

http://ift.tt/2p6uanJ

Selective binding and controlled release of anticancer drugs by polyanionic cyclodextrins

Publication date: Available online 10 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Jian-Guang Cheng, Hua-Jiang Yu, Yong Chen, Yu Liu
The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin(H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin(H2), mono-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin (H3) and mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin (H4), with three anticancer drugs, i.e. irinotecan hydrochloride; topotecan hydrochloride; doxorubicin hydrochloride, were investigated by means of ¹H NMR, UV-Vis spectroscopy, mass spectra and 2D NMR. Polyanionic cyclodextrins H1-H2 showed the significantly high binding abilities of up to 2.6 × 10⁴∼2.0 × 10⁵ M^-1 towards the selected anticancer drugs, which were nearly 50-1000 times higher than the corresponding Ks values of native β-cyclodextrin. In addition, these polyanionic cyclodextrins also showed the pH-controlled release behaviors. That is, the anticancer drugs could be efficiently encapsulated in the cyclodextrin cavity at a pH value similar to that of serum but sufficiently released at an endosomal pH value of a cancer cell, which would make these cyclodextrin derivatives the potential carriers for anticancer drugs.

Graphical abstract

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Structure–activity relationships of succinimidyl-Cys-C(O)-Glu derivatives with different near-infrared fluorophores as optical imaging probes for prostate-specific membrane antigen

Publication date: Available online 10 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Daiko Matsuoka, Hiroyuki Watanabe, Yoichi Shimizu, Hiroyuki Kimura, Yusuke Yagi, Ryoko Kawai, Masahiro Ono, Hideo Saji
Prostate-specific membrane antigen (PSMA), which is overexpressed in malignant prostate cancer (PCa), is an ideal target for imaging and therapy of PCa. We previously reported a PSMA imaging probe, 800CW-SCE, based on succinimidyl-Cys-C(O)-Glu (SCE) for optical imaging of PCa. In this study, we investigated the structure–activity relationships of novel SCE derivatives with five different near-infrared (NIR) fluorophores (IRDye 680LT, IRDye 750, Indocyanine Green, Cyanine 5.5, and Cyanine 7) as optical imaging probes targeting PSMA. An in vitro binding assay revealed that 800CW-SCE, 680LT-SCE, and 750-SCE exhibited higher binding affinity than 2-PMPA, which is known as a PSMA inhibitor. These three SCE derivatives were internalized into PSMA-positive cells (LNCaP cells) but not into PSMA-negative cells (PC-3 cells). In the in vivo imaging study, 800CW-SCE and 750-SCE were highly accumulated in LNCaP tumors but not in PC-3 tumors, and the ratio of LNCaP/PC-3 accumulation of 800CW-SCE was higher than that of 750-SCE. The present study may provide valuable molecular design information for the future development of new PSMA imaging probes based on the SCE scaffold.

Graphical abstract

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Synthesis, structure-activity relationships and preliminary mechanism study of N-benzylideneaniline derivatives as potential TLR2 inhibitors

Publication date: Available online 10 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Shaoyi Cai, Gengzheng Zhu, Xiaohong Cen, Jingjie Bi, Jingru Zhang, Xiaoshan Tang, Kun Chen, Kui Cheng
Toll-like receptor 2 (TLR2) can recognize pathogen-associated molecular patterns to defense against invading organisms and has been represents an attractive therapeutic target. Until today, none TLR2 small molecule antagonist have been developed in clinical trial. Herein, we designed and synthesized 50 N-benzylideneaniline compounds with the help of CADD. And subsequent in vitro studies leading to the optimized compound SMU-A0B13 with most potent inhibitory activity to TLR2 (IC50=18.21 ± 0.87 μM). Preliminary mechanism studies indicated that this TLR2 inhibitor can work through the NF-κB signaling pathway with high specificity and low toxicity, and can also efficiently downregulate inflammatory cytokines, such as SEAP, TNF-α and NO in HEK-Blue hTLR2, human PBMC and Raw 264.7 cell lines. Additionally, the docking situation also indicate SMU-A0B13 can well bind to the TLR2-TIR (PDB: 1FYW) active domain, which probably explains the bioactivity.

Graphical abstract

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Neuronal autophagy and intercellular regulation of homeostasis in the brain

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Aditi Kulkarni, Jessica Chen, Sandra Maday
Neurons are particularly dependent on robust quality control pathways to maintain cellular homeostasis and functionality throughout their extended lifetime. Failure to regulate protein and organelle integrity is linked to devastating neurodegenerative diseases. Autophagy is a lysosomal degradation pathway that maintains homeostasis by recycling damaged or aged cellular components. Autophagy has important functions in development of the nervous system, as well as in neuronal function and survival. In fact, defects in autophagy underlie neurodegeneration in mice and humans. Here, we review the compartment-specific dynamics and functions for autophagy in neurons. Emerging evidence suggests novel pathways for the intercellular coordination of quality control pathways between neurons and glia to maintain homeostasis in the brain.



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Axonal transport and maturation of lysosomes

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Shawn M Ferguson
Lysosomes perform degradative functions that are important for all cells. However, neurons are particularly dependent on optimal lysosome function due to their extremes of longevity, size and polarity. Axons in particular exemplify the major spatial challenges faced by neurons in the maintenance of lysosome biogenesis and function. What impact does this have on the regulation and functions of lysosomes in axons? This review focuses on the mechanisms whereby axonal lysosome biogenesis, transport and function are adapted to meet neuronal demand. Important features include the dynamic relationship between endosomes, autophagosomes and lysosomes as well as the transport mechanisms that support the movement of lysosome precursors in axons. A picture is emerging wherein intermediates in the lysosome maturation processes that would only exist transiently within the crowded confines of a neuronal cell body are spatially and temporally separated over the extreme distances encountered in axons. Axons may thus offer significant opportunities for the analysis of the mechanisms that control lysosome biogenesis. Insights from the genetics and pathology of human neurodegenerative diseases furthermore emphasize the importance of efficient axonal transport of lysosomes and their precursors.



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The electrical significance of axon location diversity

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Maarten HP Kole, Romain Brette
The axon initial segment (AIS) is a unique domain of the proximal axon serving critical electrical and structural roles including the initiation of action potentials and maintenance of cellular polarity. Recent experimental and theoretical advances demonstrate that the anatomical site for initiation is remarkably diverse. The AIS location varies not only axially, along the axon, but axons also emerge variably from either the soma or proximal dendrites. Here, we review the evidence that the diversity of AIS and axon location has a substantial impact on the electrical properties and speculate that the anatomical heterogeneity of axon locations expands synaptic integration within cell types and improves information processing in neural circuits.



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Advances in understanding neural mechanisms of social dominance

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Tingting Zhou, Carmen Sandi, Hailan Hu
Dominance hierarchy profoundly impacts social animals' survival, physical and mental health and reproductive success. As the measurements of dominance hierarchy in rodents become established, it is now possible to understand the neural mechanism mediating the intrinsic and extrinsic factors determining social hierarchy. This review summarizes the latest advances in assay development for measuring dominance hierarchy in laboratory mice. It also reviews our current understandings on how activity and plasticity of specific neural circuits shape the dominance trait and mediate the 'winner effect'.



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Effect of language experience on selective auditory attention: An event-related potential study

Publication date: Available online 9 March 2018
Source:International Journal of Psychophysiology
Author(s): Pia Rämä, Alina Leminen, Satu Koskenoja-Vainikka, Miika Leminen, Kimmo Alho, Teija Kujala
Dual language experience has typically been shown to improve various executive control functions. We investigated with event-related brain potentials (ERPs) recorded from early (natively) bilingual speakers and control participants whether it also affects auditory selective attention. We delivered to our participants two tone streams, one to the left and one to the right ear. Both streams consisted of standard tones and two types of infrequent deviant tones which had either an enhanced duration or intensity. The participants were instructed to attend either to the right or left stream and to detect longer-duration deviants in the attended stream. The results showed that the early bilinguals did not outperform the controls in target detection accuracy or speed. However, the late portion of the attention-related ERP modulation (the negative difference, Nd) was larger over the left hemisphere in the early bilinguals than in the controls, suggesting that the maintenance of selective attention or further processing of selectively attended sounds is enhanced in the bilinguals. Moreover, the late reorienting negativity (RON) in response to intensity-deviant tones was larger in the bilinguals, suggesting more efficient disengagement of attention from distracting auditory events. Hence, our results demonstrate that brain responses associated with certain aspects of auditory attention are enhanced in the bilingual adults, indicating that early dual language exposure modulates the neuronal responsiveness of auditory modality.



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Rationnel biologique de l’immunothérapie des cancers

Publication date: Available online 7 February 2018
Source:Revue des Maladies Respiratoires
Author(s): J. Benzaquen, C.-H. Marquette, N. Glaichenhaus, S. Leroy, P. Hofman, M. Ilié
IntroductionL'immunothérapie vise à promouvoir la réponse immunitaire anticancéreuse via une réponse immune contre certains antigènes tumoraux.État des connaissancesL'immunosurveillance module l'immunogénicité des tumeurs. Pour être efficace, elle doit comporter l'activation de lymphocytes T CD4⁺ et CD8⁺ et de l'immunité innée. Des molécules de costimulation activatrices et inhibitrices régulent l'activation lymphocytaire T au niveau de checkpoints de l'immunité notamment PD-1/PD-L1 et CTLA-4. La résistance immunitaire adaptative est un mode de résistance des tumeurs à l'immunosurveillance par le biais de ces checkpoints.PerspectivesLa combinaison de plusieurs immunothérapies entre elles ou avec la chimiothérapie et la radiothérapie et des anticorps contre d'autres molécules de costimulation sont en développement. Le développement de biomarqueurs capables de sélectionner une population cible et de prédire cette réponse thérapeutique représente un défi majeur. Le séquençage haut débit des tumeurs pourrait permettre d'affiner « l'immunoscore ». Le TCR intratumoral semble représenter un biomarqueur prometteur.ConclusionsLe développement de l'immunothérapie pose de nombreux défis et nécessitera de s'appuyer sur des données de recherche préclinique et translationnelle.IntroductionImmunotherapy aims to promote the immune system's activity against malignant cells by stimulating the response to several tumor antigens.State of the artImmunosurveillance may adjust the immunogenicity of tumors. To be effective, immunity must induce the specific activation of CD4+ and CD8+ T lymphocytes, as well as activation of innate immunity. Activator and inhibitory costimulatory molecules regulate T lymphocyte activation at immunity checkpoints such as PD-1/PD-L1 and CTLA-4. Adaptive immune resistance confers tumour resistance to immunosurveillance through these immune checkpoints.PerspectivesApproaches involving the combination of several immunotherapies with each other or with chemotherapy and radiotherapy and antibodies against other molecules of costimulation are under development. The development of biomarkers, which can select a targeted population and predict therapeutic response, represents a major challenge. Tumour high-throughput sequencing could refine "immunoscore". Intratumoral T cell receptor seems to represent a promising biomarker.ConclusionsNumerous challenges still remain in developing research approaches for the development of immunotherapies.



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Zika virus: From an obscurity to a priority

Publication date: Available online 9 March 2018
Source:Microbes and Infection
Author(s): Cheryl Yi-Pin Lee, Lisa F.P. Ng
Despite being discovered approximately 70 years ago, Zika virus (ZIKV) has received little attention, until the occurrence of alarming epidemics in the Pacific Islands and Latin America between 2013 and 2016. These series of outbreaks resulted in crippling neurological complications in adults, and congenital deformities in new-borns. The dire outcomes marked ZIKV as a re-emerging pathogen of public health concern. Over a period of two years, extensive studies have been conducted to understand different aspects of ZIKV from pathogen biology to infection, including the immune response during virus-host interplay in established animal models, as well as potential therapeutics against ZIKV infection. The vast diversity of novel findings has added value to ZIKV research, and a strategic consolidation is crucial to encompass the latest advances and developments, as well as missing pieces of the puzzle. This review thus aims to provide a concise yet extensive update on current ZIKV studies.



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Editorial board

Publication date: February 2018
Source:Microbes and Infection, Volume 20, Issue 2





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Regional-level exchange in Postclassic Central Mexico

Publication date: June 2018
Source:Journal of Anthropological Archaeology, Volume 50
Author(s): Angela C. Huster
This article uses evidence of regional-scale ceramic exchange to evaluate three proposed causal factors (Aztec imperial expansion, bottom-up demand, and elite competition) for the development of the market-based economy of Postclassic Central Mexico. The factors used to evaluate these models may be applied more widely to other cases of market development. Using previously published datasets, I compare the quantities and diversities of non-local ceramics from sites in the Basin of Mexico, Morelos, and the Toluca Valley regions of central highland Mexico across the Middle (CE 1150–1350) and Late (CE 1350–1521) Postclassic periods. The results show that the highest proportion of trade occurs under Aztec rule, and is dominated by ceramics exported out of the Basin of Mexico. However, areas outside the Basin of Mexico have higher numbers of trading partners, and these ties are well developed during the Middle Postclassic. These results provide partial support for both bottom-up demand and elite competition as causal factors for market development. This article also demonstrates the continued utility of legacy data and emphasizes the need to make basic data sets available for new analyses.



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Autopsy Neuropathology Findings in a Child with Chronic Infantile Krabbe Leukoencephalopathy

Publication date: Available online 9 March 2018
Source:Pediatric Neurology
Author(s): Marc R. Del Bigio




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Passing the Newborn Hearing Screen Does Not Always Exclude Infectious Congenital Acquired Hearing Loss

Publication date: Available online 8 February 2018
Source:Pediatric Neurology
Author(s): Elizabeth Sabroske, Melissa D. Svoboda, Yu-Tze Ng




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Abobotulinumtoxina Efficacy and Safety in Children with Equinus Foot Previously Treated with Botulinum Toxin

Publication date: Available online 7 February 2018
Source:Pediatric Neurology
Author(s): Edward Dabrowski, Marcin Bonikowski, Mark Gormley, Magali Volteau, Philippe Picaut, Mauricio R. Delgado
BackgroundThe effects of botulinum toxin are transient, and repeat injections are required in children with lower-limb spasticity. However, the efficacy of botulinum toxin in patients who have received previous injections has remained largely unexplored.MethodsWe present subgroup analyses of a Phase III study conducted in ambulatory children (aged 2–17) with spastic equinus foot. Patients were randomized to single doses of abobotulinumtoxinA 10U/kg/leg, 15U/kg/leg or placebo injected into the gastrocnemius-soleus complex (one/both legs). The first analysis was pre-specified to review the effect of abobotulinumtoxinA in children previously treated with botulinum toxin versus those new to the treatment; a second post-hoc analysis evaluated the effect of abobotulinumtoxinA in children who changed botulinum toxin formulation.ResultsOf the 241 randomized patients, 113 had previously received botulinum toxin, including 86 who had been treated with another formulation. In both analyses, muscle tone (modified Ashworth Scale) and the Physicians Global Assessment at week- 4 improved with abobotulinumtoxinA treatment versus placebo, regardless of baseline botulinum toxin status. Placebo responses in patients new to treatment were consistently higher than in the previously treated group.ConclusionsThese results demonstrate similar abobotulinumtoxinA efficacy and safety profiles in children with spasticity who are new to botulinum toxin treatment and those previously treated. The efficacy and safety of abobotulinumtoxinA treatment in these previously-treated patients were comparable with the overall trial population, indicating that doses of 10U/kg/leg and 15 U/kg/leg are suitable starting doses for children with spasticity regardless of the previous botulinum toxin preparation used.



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Poliosis in a Child with Possible Rare Association.

Publication date: Available online 7 February 2018
Source:Pediatric Neurology
Author(s): Lalit Bansal, Timothy P. Zinkus, Alexander Kats




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A Highly Sensitive and Specific Combined Clinical and Sonographic Score to Diagnose Appendicitis

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Benjamin Sholl




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American Academy of Emergency Medicine

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3





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CHA2DS2-VASc Score for Identifying Truly Low-Risk Atrial Fibrillation for Stroke. A Korean Nationwide Cohort Study

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Krysia Crabtree




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Atraumatic Clostridial Myonecrosis in an Immunocompromised Host

Publication date: Available online 10 March 2018
Source:The Journal of Emergency Medicine
Author(s): Kristine M. Thompson, Brian T. Kruse, Mary Ann S. Hedges
BackgroundNecrotizing fasciitis is usually associated with a surgical or traumatic wound. Clostridial myonecrosis is an uncommon but deadly infection that can develop in the absence of a wound and is often associated with occult gastrointestinal cancer or immunocompromise, or both.Case ReportWe report a case of catastrophic atraumatic Clostridium septicum infection in an immunocompromised host.Why Should an Emergency Physician Be Aware of This?Emergency physicians most commonly associate necrotizing fasciitis with superinfection of an open wound. This case reminds physicians that patients with acquired neutropenia can present with spontaneous gas gangrene due to C. septicum. Providers should consider this diagnosis in immunocompromised patients who present with acute onset of severe atraumatic limb pain.



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Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo)

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Paul Leccese




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Impact of Implementing National Guidelines on Antibiotic Prescriptions for Acute Respiratory Tract Infections in Pediatric Emergency Departments: An Interrupted Time Series Analysis

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Krysia Crabtree




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Ultrasound-Guided Dynamic Needle Tip Positioning Technique Versus Palpation Technique for Radial Arterial Cannulation in Adult Surgical Patients: A Randomized Control Trial

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Grant Thomas Comstock




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Editorial Board

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3





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Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of Efficacy

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Leslie S. Zun
BackgroundThe main goal of antipsychotic medication in the management of acute agitation in the emergency department is to rapidly induce calm without oversedation, enabling patients to participate in their own care. However, there is a paucity of comparative studies, particularly with newer fast-acting second-generation antipsychotic agents.Objective of the ReviewThis structured evidence-based review compared the onset of efficacy of antipsychotic treatments for acute agitation using data from randomized controlled trials identified by a literature search of the PubMed database.ResultsBased on findings from 28 blinded randomized controlled trials, onset of efficacy was rapid and generally observed at the first time point after intramuscular administration of ziprasidone (15−30 min) or olanzapine (15−30 min), but was more likely to be delayed with intramuscular haloperidol, even when combined with lorazepam (30−60 min), and intramuscular aripiprazole (45−90 min). When administered orally, rapid onset of efficacy was also consistently observed at the first assessment time point with olanzapine (15−120 min), risperidone (30−120 min), and sublingual asenapine (15 min). Significant effects were apparent for inhaled loxapine within 10−20 min. Effects were apparent within approximately 5−10 min with i.v. droperidol. Onset of efficacy was typically more rapid with second-generation antipsychotic agents than benzodiazepines, but data are limited.ConclusionsAlthough the patient populations of trials included in this review do not truly reflect that of the emergency department, the results provide useful information to emergency physicians on the rapid efficacy of certain newer-generation antipsychotic agents for the treatment of acutely agitated patients.



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Issue Highlights

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3





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Contents

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3





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Partial Contents of Volume 54, Number 4

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3





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Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Paul A. Leccese




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Increased Mortality in Trauma Patients Who Develop Postintubation Hypotension

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Paul Leccese




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Comparison of the Mallampati Classification in Sitting and Supine Position to Predict Difficult Tracheal Intubation: A Prospective Observational Cohort Study

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Krysia Crabtree




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Do Emergency Physicians Improve the Appropriateness of Emergency Transfer in Rural Areas?

Publication date: March 2018
Source:The Journal of Emergency Medicine, Volume 54, Issue 3
Author(s): Ji Hoon Kim, Min Joung Kim, Je Sung You, Mi Kyung Song, Sung il Cho
BackgroundUntil recently, there have been few studies on the transfer of patients from emergency departments (EDs) overall, as such studies were limited primarily to trauma patients.ObjectivesThe purpose of this study was to investigate the association between the specialty of the primary referring physician and the appropriateness of the emergency transfer (AET).MethodsThis was a retrospective, observational study performed at two level-3 EDs in a rural area. A transfer to a higher-level ED for the purpose of patient stabilization was defined as an emergency transfer, and transfers were classified as "appropriate" when the emergency status of the patient could not be resolved by the referring ED. The primary outcome was AET, which was reviewed by an expert panel for reliability. Statistically significant variables were selected as covariates based on the results of a univariate analysis, and a multivariate logistic regression analysis was performed to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) on the AET.ResultsA total of 1325 patients underwent transfer to another hospital from the two EDs. Of these, 1003 were classified into the emergency transfer group. In both EDs, the incidence of appropriate emergency transfers was significantly higher when the primary referring physician was an emergency physician (OR 4.005, 95% CI 2.619–6.125 and OR 4.006, 95% CI 1.696–9.459 for each hospital, respectively).ConclusionThere was a positive association between the specialty of the primary referring physician and the AET among EDs located in rural areas making patient transfers.



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Surfactant-enhanced biodegradation of crude oil by mixed bacterial consortium in contaminated soil

Abstract

This study evaluated the effects of two surfactants (i.e., Tween 80 and SDS) on biodegradation of crude oil by mixed bacterial consortium in soil-aqueous system. The mixed bacterial consortium was domesticated from the activated sludge of cooking plant through a progressive domestication process. High-throughput sequencing analysis revealed that Rhodanobacter sp. was the dominant bacteria. The higher CMC_eff value for two surfactants was observed in soil-aqueous system compared with that in aqueous system, which was likely due to their adsorption onto soil particles. Either Tween 80 or SDS can be utilized as carbon source and promote the growth of mixed bacterial consortium. Further findings evidenced that the degradation of crude oil can be enhanced by adding either Tween 80 or SDS. The performance of Tween 80 was generally superior to SDS for the crude oil degradation. The highest crude oil degradation efficiency was 42.2 and 31.0% under the conditions of 5 CMC_eff of Tween 80 and 2 CMC_eff of SDS, respectively. Furthermore, the degradation efficiency of crude oil in remediation experiment (i.e., 77%) evidenced that the integration of adding Tween 80 and inoculating mixed bacterial consortium was effective for crude oil-contaminated soil decontamination.

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Development of an in vitro toxicological test system based on zebrafish ( Danio rerio ) sperm analysis

Abstract

The effect of seven heavy metals on the motility parameter of zebrafish sperm was tested in order to develop an in vitro toxicological test system as an alternative to live animal testing. In vitro test systems are currently preferred in ecotoxicology due to their practical and ethical advantages and fish sperm can be a suitable model. A number of studies had been carried out previously on this topic, but the described methods had not been standardized in numerous aspects (donor species, measured endpoint, etc.). In this study, heavy metals (mercury, arsenic, chromium, zinc, nickel, copper, cadmium) were used as reference toxicants with known toxicity to develop a standardized fish sperm in vitro assay. The tested concentrations were determined based on preliminary range finding tests. The endpoints were progressive motility (PMOT, %), curvilinear velocity (VCL, μm/s), and linearity (LIN, %) measured by a computer-assisted sperm analysis (CASA) system. According to our results, PMOT was the most sensitive of the three investigated parameters: dose-response curves were observed for each metal at relatively low concentrations. VCL values were less sensitive: higher concentrations were needed to observe changes. Of the three parameters, LIN was the least affected: dose-response relationship was observed only in the case of mercury (e.g., lowest observed effect concentration (LOEC) of Hg at 120 min: 1 mg/L for PMOT, 2.5 mg/L for VCL, 5 mg/L for LIN; LOEC of Cu at 120 min: 1 mg/L for PMOT, 5 mg/L for VCL, any for LIN). The order of toxicity as determined by PMOT was as follows: Hg²⁺ > As³⁺ > Cd²⁺ > Cu²⁺ > Zn²⁺ > Cr³⁺ > Ni²⁺. In conclusion, we found that PMOT of zebrafish sperm was an accurate and fast bioindicator of heavy metal load. Sperm analysis can be adopted to estimate the possible toxic effects of various chemicals in vitro. Future investigations should concentrate on the applicability of this assay to other contaminants (e.g., organic pollutants).

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RARA and RARG Gene Downregulation Associated with EZH2 Mutation in Acute Promyelocytic-Like Morphology Leukemia

Publication date: Available online 10 March 2018
Source:Human Pathology
Author(s): Nicoletta Coccaro, Antonella Zagaria, Paola Orsini, Luisa Anelli, Giuseppina Tota, Paola Casieri, Luciana Impera, Angela Minervini, Crescenzio F. Minervini, Cosimo Cumbo, Elisa Parciante, Anna Mestice, Mario Delia, Claudia Brunetti, Giorgina Specchia, Francesco Albano
Most Acute Promyelocytic Leukemia (APL) patients express PML-RARA fusion; in rare cases RARA is rearranged with partner genes other than PML. To date, only two patients presenting features similar to APL showing the RARG gene rearrangement have been described. We report an Acute Myeloid Leukemia (AML) patient with morphology resembling APL without involvement of the RARA gene. Molecular and Fluorescent In Situ Hybridization (FISH) analyses excluded PML-RARA fusion and variant rearrangements involving RARA and RARG loci. Targeted Next Generation Sequencing showed EZH2-D185H mutation. As this mutation involved the region of interaction with DNA methyltransferases, we speculate an epigenetic alteration of genes involved in the APL-like phenotype. Expression analysis by droplet digital Polymerase Chain Reaction (PCR) revealed downregulation of the RARA and RARG genes. We hypothesize a novel mechanism of EZH2 function alteration, which may be responsible for an AML with APL-like phenotype featuring dysregulation of the RARA and RARG genes.



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A unique evolution of the kidney phenotype in a patient with autosomal recessive Alport syndrome

Publication date: Available online 9 March 2018
Source:Human Pathology
Author(s): Gisella Vischini, Meghan E. Kapp, Ferrin C. Wheeler, Laszlo Hopp, Agnes B. Fogo
Alport syndrome is due to mutations in one of the genes encoding (α3,4,5) type IV collagen resulting in defective type IV collagen, a key component of the glomerular basement membrane (GBM). The GBM is initially thin, and with ongoing remodeling, develops a thickened basket-woven appearance. We report a unique case of a 9-year-old boy who was biopsied for hematuria and proteinuria, diagnosed as IgA nephropathy, with normal GBM appearance and thickness. Due to a family history of hematuria and chronic kidney disease, he subsequently underwent genetic evaluation and a mutation of α3 type IV collagen (COL4A3) was detected. Additional studies of the initial biopsy demonstrated abnormal type IV collagen immunostaining. A repeat biopsy 4years later showed characteristic glomerular basement membrane morphology of Alport syndrome, and scarring consistent with sequelae of IgA nephropathy. This is the first description of this unusual transition from an initial normal appearance of the glomerular basement membrane to the classic Alport phenotype.



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Evaluation of the fit of zirconia copings fabricated by direct and indirect digital impression procedures

Publication date: Available online 7 February 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Bora Lee, Kyung Chul Oh, Daewon Haam, Joon-Hee Lee, Hong-Seok Moon
Statement of problemIntraoral scanners are effective for direct digital impression when dental restorations are fabricated using computer-aided design and computer-aided manufacturing (CAD-CAM); however, if the abutment tooth cannot be dried completely or the prepared margin is placed subgingivally, accurate digital images cannot always be guaranteed.PurposeThe purpose of this in vitro study was to compare the internal and marginal discrepancies of zirconia copings fabricated directly using an intraoral scanner with those fabricated indirectly with impression scanning.Material and methodsForty-five resin dies fabricated with a 3-dimensional (3D) printer were divided into 3 groups: direct scanning (DS), impression scanning (IMP), and lost-wax casting (LW). For the DS group, a resin die was scanned with an intraoral scanner (Trios; 3Shape), whereas for the IMP group, impressions made with polyether were scanned with a cast scanner (D700; 3Shape). The zirconia copings were fabricated in the same way in the DS and IMP groups. For the LW group, impressions were made in the same way as in the IMP group, and Ni-Cr alloy copings were fabricated using LW. The marginal and internal discrepancies of the copings were measured by cementing them onto resin dies, embedding them in acrylic resin, and sectioning them in a buccolingual direction. The cement layer was measured, and the Kruskal-Wallis test was used to detect significant differences (α=.05). A nonparametric Friedman test was also performed to compare the measurements of each group by location (α=.05).ResultsThe mean marginal discrepancies in the DS, IMP, and LW groups were 18.1 ±9.8, 23.2 ±17.2, and 32.3 ±18.6 μm (mean ±standard deviation), respectively. The mean internal discrepancies of the DS, IMP, and LW groups in the axial area were 38.0 ±9.1, 47.0 ±16.3, and 36.5 ±15.8 μm, and those in the occlusal area were 36.7 ±16.9, 33.4 ±21.6, and 44.5 ±31.9 μm, respectively. No statistically significant differences were found in marginal or internal discrepancies among groups (P>.05).ConclusionsWithin the limitations of this study, the zirconia copings fabricated with CAD-CAM using different digitization methods and Ni-Cr copings fabricated using the lost-wax technique and casting produced clinically acceptable marginal and internal discrepancies. No significant differences were found among the DS, IMP, and LW groups.



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Improved isolation of cadmium from paddy soil by novel technology based on pore water drainage with graphite-contained electro-kinetic geosynthetics

Abstract

Novel soil remediation equipment based on electro-kinetic geosynthetics (EKG) was developed for in situ isolation of metals from paddy soil. Two mutually independent field plot experiments A and B (with and without electric current applied) were conducted. After saturation using ferric chloride (FeCl₃) and calcium chloride (CaCl₂), soil water drainage capacity, soil cadmium (Cd) removal performance, energy consumption as well as soil residual of iron (Fe) and chloride (Cl) were assessed. Cadmium dissolved in the soil matrix and resulted in a 100% increase of diethylenetriamine-pentaacetic acid (DTPA) extracted phyto-available Cd. The total soil Cd content reductions were 15.20% and 26.58% for groups A and B, respectively, and electric field applications resulted in a 74.87% increase of soil total Cd removal. The electric energy consumption was only 2.17 kWh/m³ for group B. Drainage by gravity contributed to > 90% of the overall soil dewatering capacity. Compared to conventional electro-kinetic technology, excellent and fast soil water drainage resulted in negligible hydrogen ion (H⁺) and hydroxide ion (OH⁻) accumulation at nearby electrode zones, which addressed the challenge of anode corrosion and cathode precipitation of soil metals. External addition of FeCl₃ and CaCl₂ caused soil Fe and Cl residuals and led to 4.33–7.59% and 139–172% acceptable augments in soil total Fe and Cl content, correspondingly, if compared to original untreated soils. Therefore, the novel soil remediation equipment developed based on EKG can be regarded as a promising new in situ technology for thoroughly isolating metals from large-scale paddy soil fields.

http://ift.tt/2txvZiZ

Toxicity bioassays with concentrated cell culture media—a methodology to overcome the chemical loss by conventional preparation of water samples

Abstract

The use of in vitro bioassays for studies of toxic activity in environmental water samples is a rapidly expanding field of research. Cell-based bioassays can assess the total toxicity exerted by a water sample, regardless whether the toxicity is caused by a known or unknown agent or by a complex mixture of different agents. When using bioassays for environmental water samples, it is often necessary to concentrate the water samples before applying the sample. Commonly, water samples are concentrated 10–50 times. However, there is always a risk of losing compounds in the sample in such sample preparation. We have developed an alternative experimental design by preparing a concentrated cell culture medium which was then diluted in the environmental water sample to compose the final cell culture media for the in vitro assays. Water samples from five Swedish waste water treatment plants were analyzed for oxidative stress response, estrogen receptor (ER), and aryl hydrocarbon receptor (AhR) activity using this experimental design. We were able to detect responses equivalent to 8.8–11.3 ng/L TCCD for AhR activity and 0.4–0.9 ng/L 17β-estradiol for ER activity. We were unable to detect oxidative stress response in any of the studied water samples. In conclusion, we have developed an experimental design allowing us to examine environmental water samples in toxicity in vitro assays at a concentration factor close to 1, without the risk of losing known or unknown compounds during an extraction procedure.

http://ift.tt/2FIomLB

Mortality assessment attributed to long-term exposure to fine particles in ambient air of the megacity of Tehran, Iran

Abstract

Few studies regarding the health effects of long-term exposure to particulate matter with an aerodynamic diameter of 2.5 μm or less (PM_2.5) have been carried out in Asia or the Middle East. The objective of our study was to assess total, lung cancer and chronic obstructive pulmonary disease (COPD) mortality attributed to long-term exposure to PM_2.5 among adults aged over 30 years in Tehran from March 2013 to March 2016 using AirQ⁺ software. AirQ⁺ modeling software was used to estimate the number of deaths attributed to PM_2.5 concentrations higher than 10 μg m⁻³. Air quality data were obtained from the Department of Environment (DOE) and Tehran Air Quality Control Company (TAQCC). Only valid stations with data completeness of 75% in all 3 years were selected for entry into the model. The 3-year average of the 24-h concentrations was 39.17 μg m⁻³. The results showed that the annual average concentration of PM_2.5 in 2015–2016 was reduced by 13% compared to that in 2013–2014. The annual average number of all natural, COPD, and lung cancer deaths attributable to long-term exposure to PM_2.5 in adults aged more than 30 years was 5073, 158, and 142 cases, respectively. The results of all three health endpoints indicate that the mortality attributable to PM_2.5 decreased yearly from 2013 to 2016 and that the reduced mortality was related to a corresponding reduction in the PM_2.5 concentration. Considering these first positive results, the steps that have been currently taken for reducing air pollution in Tehran should be continued to further improve the already positive effects of these measures on reducing health outcomes.

http://ift.tt/2tzQRpS

Effect of microalgae storage conditions on methane yields

Abstract

During the last decade, a lot of research has been focused on identifying the methane yields achievable when using microalgae biomass (fresh and pretreated) as a substrate in anaerobic digestion. Encountered differences are frequently attributed to the different microalgae strains (cell walls and macromolecular profiles) or the different metabolic activities of anaerobic sludge used as inoculum. Nevertheless, under the hypothesis that the state of microalgae upon biomass storage may also play a significant role, this study was designed to evaluate the effect of biomass processing and storage on methane yields and hydrolysis kinetics in batch mode assays. Slight changes in the macromolecular profile distribution of the different tested biomass were observed. Regardless of the time that the biomass was stored, results revealed that frozen biomass doubled the hydrolysis constant and enhanced methane yield by 1.56-fold compared to fresh microalgae biomass (82.4 mL CH₄ g COD in⁻¹). Similar enhancement was obtained with the freeze-dried biomass, and slightly lower values were obtained (1.34-fold) for the biomass kept at 4 °C longer than a week. Likewise, the semi-continuously operated reactor fed with microalgae biomass stored for 28 days at 4 °C did not show any effect in terms of methane production, although nitrogen mineralization was higher than expected. Remarkably, the initial stage of the biomass should be carefully considered for comparison purposes with the available literature on batch mode assays. This study highlights the importance of considering how the biomass is stored before the anaerobic digestion process to avoid misleading conclusions.

http://ift.tt/2FH3F2M

On the flocculation and settling characteristics of low- and high-concentration sediment suspensions: effects of particle concentration and salinity conditions

Abstract

It remains unclear how the primary particle concentration and salinity conditions influence the flocculation and settling characteristics of water-sediment suspensions. In this study, two sets of experiments were performed to examine the flocculation and settling properties of low- and high-concentration sediment suspensions. In low-concentration suspensions, the sediment concentration undergoes a rapid initial decrease followed by a slow decrease until it approaches zero with increasing flocculation time. Increases in salinity or the valence of cations from the saline solution added to the suspension lead to a more rapidly decreasing sediment concentration with flocculation time. The valence of cations from the saline solution has a larger influence on the flocculation-settling behaviours of the suspension than the salinity. In high-concentration sediment suspensions, the height of the clear water-turbid water interface in the water-sediment suspension experiences an initial, rapidly decreasing phase followed by a slowly decreasing phase with increasing flocculation time. Increasing the primary particle concentration, salinity or valence of cations from the saline solution added to the suspension causes the height reduction of the clear water-turbid water interface to become gentler. Finally, the valence of cations from the saline solution has a greater influence on the settling characteristics of the high-concentration water-sediment suspension than the salinity.

http://ift.tt/2tyzoOB

Nano-MnO 2 -mediated transformation of triclosan with humic molecules present: kinetics, products, and pathways

Abstract

It has been shown that manganese dioxide (MnO₂) can mediate transformation of phenolic contaminants to form phenoxyl radical intermediates, and subsequently, these intermediates intercouple to form oligomers via covalent binding. However, the reaction kinetics and transformation mechanisms of phenolic contaminants with humic molecules present in nano-MnO₂-mediated systems were still unclear. In this study, it was proven that nano-MnO₂ were effective in transforming triclosan under acidic conditions (pH 3.5–5.0) during manganese reduction, and the apparent pseudo first-order kinetics rate constants (k = 0.0599–1.5314 h⁻¹) increased as the pH decreased. In particular, the transformation of triclosan by nano-MnO₂ was enhanced in the presence of low-concentration humic acid (1–10 mg L⁻¹). The variation in the absorption of humic molecules at 275 nm supported possible covalent binding between humic molecules and triclosan in the nano-MnO₂-mediated systems. A total of four main intermediate products were identified by high-resolution mass spectrometry (HRMS), regardless of humic molecules present in the systems or not. These products correspond to a suite of radical intercoupling reactions (dimers and trimers), ether cleavage (2,4-dichlorophenol), and oxidation to quinone-like products, triggered by electron transfer from triclosan molecules to nano-MnO₂. A possible reaction pathway in humic acid solutions, including homo-coupling, decomposition, oxidation, and cross-coupling, was proposed. Our findings provide valuable information regarding the environmental fate and transformation mechanism of triclosan by nano-MnO₂ in complex water matrices.

http://ift.tt/2FIodI3

US Military Dietetic Internship and Graduate Program: Retrospective Analysis of Selection Criteria and Student Success

Publication date: Available online 7 February 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Heidi L. Clark, Renee E. Cole, LesLee K. Funderburk
BackgroundThe US Military-Baylor Graduate Program in Nutrition (GPN) has a 10% 7-year attrition rate representing wasted military resources. Evidence-based selection criteria for dietetics masters of science (MS) programs do not exist, nor does descriptive information of successful students.ObjectiveIdentify GPN student characteristics predicting program success in the didactic and internship phases.DesignRetrospective study using demographic, academic, and nonacademic data extracted from existing files.Participants and settingThere were 72 GPN students enrolled from 2006 to 2013 in San Antonio, TX.Main outcome measuresCategorization by optimal performance (no course grade <3.0, no internship rotation delays, first attempt pass registered dietitian nutritionist examination) and GPN completion.ResultsThe average GPN student was female (65%), in the US Army (94%), and single (64%), with a mean age of 26 years. Mean Quantitative, Verbal Reasoning, and Analytical Writing Graduate Record Examination (GRE) scores were 149, 153, and 4.2 points, respectively. Odds of GPN failure increased 1.3 times with each year increase in age at GPN program start (95% CI=1.089 to 1.612; P=0.005). Odds of attaining optimal performance decreased 4.5 times with each additional year increase between GRE completion and GPN start (95% CI=1.623 to 16.236; P=0.005) and 0.157 times with each grade point average point decrease in Biochemistry (95% CI=0.49 to 0.430; P=0.002).ConclusionsModification of selection criteria based on time between GRE and GPN start and undergraduate Biochemistry grades could improve GPN success. However, identification and mitigation of potential student weaknesses is a more realistic approach to promote student success. Intentional development of students with optimal characteristics will strengthen the dietetics profession during the transition to an MS degree requirement.



http://ift.tt/2IdNaJQ

Association between Dietary Glycemic Index and Knee Osteoarthritis: The Korean National Health and Nutrition Examination Survey 2010-2012

Publication date: Available online 7 February 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Min Wook So, Sunggun Lee, Seong-Ho Kim
BackgroundObesity and metabolic abnormalities are important risk factors for knee osteoarthritis (KOA). Recent epidemiologic studies have found that a high glycemic index (GI) and glycemic load (GL) diet are associated with a higher risk for metabolic complications and cardiovascular mortality.ObjectiveWe aimed to examine the association between dietary GI, dietary GL, and KOA among Korean adults.DesignThis was a cross-sectional study that analyzed data obtained from the Korean National Health and Nutrition Examination Survey 2010-2012.Participants/settingA total of 9,203 participants (5,275 women) aged ≥50 years were included.Main outcome measuresKOA was defined as the presence of radiographic features of Kellgren-Lawrence grade ≥2. Chronic knee pain was defined as the presence of knee pain for more than 30 days during the past 3 months. Dietary information was collected using a single 24-hour recall method.Statistical analyses performedThe association between the quintiles of dietary GI and dietary GL and knee conditions was analyzed using a multinomial logistic regression analysis adjusting for age, physical activity, obesity, hypertension and diabetes, serum low-density lipoprotein, and total energy intake.ResultsAmong the women, the association between dietary GI and symptomatic KOA was: quintile 1: 1.00 (reference); quintile 2: 1.29 (95% CI 0.87 to 1.92); quintile 3: 1.59 (95% CI 1.11 to 2.28); quintile 4: 1.74 (95% CI 1.21 to 2.51); and quintile 5: 1.77 (95% CI 1.20 to 2.60) (P=0.001). Chronic knee pain without KOA was associated with dietary GI; however, this association was not linear across quintiles. There was no significant association between dietary GI and asymptomatic KOA. Among the men, no significant association was found between dietary GI and any knee conditions. There was no significant association between dietary GL and KOA in both men and women.ConclusionsThere was a significant positive association between dietary GI and symptomatic KOA in women.



http://ift.tt/2Dg9Q8D

Impacts of synoptic condition and planetary boundary layer structure on the trans-boundary aerosol transport from Beijing-Tianjin-Hebei region to northeast China

Publication date: May 2018
Source:Atmospheric Environment, Volume 181
Author(s): Yucong Miao, Jianping Guo, Shuhua Liu, Chun Zhao, Xiaolan Li, Gen Zhang, Wei Wei, Yanjun Ma
The northeastern China frequently experiences severe aerosol pollution in winter under unfavorable meteorological conditions. How and to what extent the meteorological factors affect the air quality there are not yet clearly understood. Thus, this study investigated the impacts of synoptic patterns on the aerosol transport and planetary boundary layer (PBL) structure in Shenyang from 1 to 3 December 2016, using surface observations, sounding measurements, satellite data, and three-dimensional simulations. Results showed that the aerosol pollution occurred in Shenyang was not only related to the local emissions, but also contributed by trans-boundary transport of aerosols from the Beiijng-Tianjin-Hebei (BTH) region. In the presence of the westerly and southwesterly synoptic winds, the aerosols emitted from BTH could be brought to Shenyang. From December 2 to 3, the aerosols emitted from BTH accounted for ∼20% of near-surface PM2.5 in Shenyang. In addition, the large-scale synoptic forcings could affect the vertical mixing of pollutants through modulating the PBL structure in Shenyang. The westerly and southwesterly synoptic winds not only brought the aerosols but also the warmer air masses from the southwest regions to Shenyang. The strong warm advections above PBL could enhance the already existing thermal inversion layers capping over PBL in Shenyang, leading to the suppressions of PBL. Both the trans-boundary transport of aerosols and the suppressions of PBL caused by the large-scale synoptic forcings should be partly responsible for the poor air quality in Shenyang, in addition to the high pollutant emissions. The present study revealed the physical mechanisms underlying the aerosol pollution in Shenyang, which has important implications for better forecasting and controlling the aerosols pollution.



http://ift.tt/2p8ucvF

Scholar : These new articles for Amyloid are available online

The online platform for Taylor & Francis Online content New for Amyloid and online now on Taylor & Francis Online: Letter to the Editor Atrial impairment in transthyretin cardiac amyloidosis: an early marker of cardiac involvement and a prognostic factor Gianluca Di Bella & Fabio Minutoli Pages: 1-1 | DOI: 10.1080/13506129.2018.1450240 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Year-long simulation of gaseous and particulate air pollutants in India

Publication date: May 2018
Source:Atmospheric Environment, Volume 180
Author(s): Sri Harsha Kota, Hao Guo, Lauri Myllyvirta, Jianlin Hu, Shovan Kumar Sahu, Rajyalakshmi Garaga, Qi Ying, Aifang Gao, Sunil Dahiya, Yuan Wang, Hongliang Zhang
Severe pollution events occur frequently in India but few studies have investigated the characteristics, sources, and control strategies for the whole country. A year-long simulation was carried out in India to provide detailed information of spatial and temporal distribution of gas species and particulate matter (PM). The concentrations of O3, NO2, SO2, CO, as well as PM2.5 and its components in 2015 were predicted using Weather Research Forecasting (WRF) and the Community Multiscale Air Quality (CMAQ) models. Model performance was validated against available observations from ground based national ambient air quality monitoring stations in major cities. Model performance of O3 does not always meet the criteria suggested by the US Environmental Protection Agency (EPA) but that of PM2.5 meets suggested criteria by previous studies. The performance of model was better on days with high O3 and PM2.5 levels. Concentrations of PM2.5, NO2, CO and SO2 were highest in the Indo-Gangetic region, including northern and eastern India. PM2.5 concentrations were higher during winter and lower during monsoon season. Winter nitrate concentrations were 160–230% higher than yearly average. In contrast, the fraction of sulfate in total PM2.5 was maximum in monsoon and least in winter, due to decrease in temperature and solar radiation intensity in winter. Except in southern India, where sulfate was the major component of PM2.5, primary organic aerosol (POA) fraction in PM2.5 was highest in all regions of the country. Fractions of secondary components were higher on bad days than on good days in these cities, indicating the importance of control of precursors for secondary pollutants in India.

Teaser

Capsule abstract: Predicted gaseous and particulate air pollutants in India using WRF/CMAQ in 2015 were validated and the variations were analyzed for future source and health analysis.


http://ift.tt/2IjyEAf

Scholar : These new articles for Journal of Architectural Conservation are available online

The online platform for Taylor & Francis Online content New for Journal of Architectural Conservation and online now on Taylor & Francis Online: Original Articles Standardizing the indoor climate in historic buildings: opportunities, challenges and ways forward | Gustaf Leijonhufvud & Tor Broström Pages: 1-16 | DOI: 10.1080/13556207.2018.1447301 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Blood pressure variability in primary hyperparathyroidism: more data needed

http://ift.tt/2Ij8uO8