Notes

Uncommon presentation regarding infective endocarditis in ICU.
Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activity against prostate and other cancers but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids, and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A). Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of ACC1 and FASN protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ACLY, ACC1, FASN, and CPT1A proteins in the prostate in vivo. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email [email protected] We assessed prevalence of testing for HIV and hepatitis C virus (HCV) infection among persons who inject drugs (PWID). METHODS Using a nationwide health insurance database for claims paid during 2010-2017, we identified PWID by using codes from the International Classification of Diseases, Current Procedural Terminology, and National Drug Codes directory. We then estimated the percentage of PWIDs tested for HIV or HCV within 1 year of an index encounter, and used multivariate logistic regression models to assess demographic and clinical factors associated with testing. RESULTS Of 844 242 PWIDs, 71 938 (8.5%) were tested for HIV and 65 188 (7.7%) for HCV infections. Missed opportunities were independently associated with being male (ORs HIV, 0.50 [95% CI, 0.49-0.50]; P less then .001; HCV, 0.66 [95% CI, 0.65-0.72]; P less then .001), rural residence (ORs HIV, 0.67 [95% CI, 0.65-0.69]; P less then .001; HCV, 0.75 [95% CI, 0.73-0.77]), and receiving services for skin infections or endocarditis (aORs HIV, 0.91 [95% CI, 0.87-0.95]; P less then .001; HCV, 0.90 [95% CI, 0.86-0.95]; P less then .001). CONCLUSION Approximately 90% of presumed PWIDs missed opportunities for HIV or HCV testing, especially male rural residents with claims for skin infections or endocarditis, commonly associated with injection drug use. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.Several Agriotes click beetle species are important pests of vegetables and field crops. Monitoring for beetles is generally done with pheromone-baited traps maintained in permanent locations. Since dispersal is mostly by walking, such traps may deplete populations around them, leading to underestimations of populations relative to nontrapped areas, and of concomitant risk of wireworm damage to nearby crops. We placed sets of five pitfall traps in field headland areas in 2015-2017, of which two were baited with Agriotes obscurus (L) or Agriotes lineatus (L) (Coleoptera Elateridae) pheromone. Of these, one was maintained in a permanent location, while the other moved among the remaining positions. Traps were checked weekly over the emergence period. For A. obscurus, fixed and moving traps initially collected similar numbers, but the latter collected significantly more later in the season, indicating depletion around fixed traps. Depletion was most pronounced after a period of cold weather, and around the peak swarming period. Depletion observed for A. lineatus was not statistically significant. This indicates pheromone-baited traps used for walking insects can underestimate populations, but depletion rates vary with species and temperature and should be accounted for when traps are used to develop action thresholds or time control strategies. Selleck SU1498 © Her Majesty the Queen in Right of Canada, as represented by the Minister of Agriculture, 2020. All rights reserved. For permissions, please e-mail [email protected], 622 imputations were conducted with 394 customized reference panels for Han Chinese and European populations. Besides validating the fact that imputation accuracy could always benefit from the increased panel size when the reference panel was population specific, the results brought two new thoughts. First, when the haplotype size of the reference panel was fixed, the imputation accuracy of common and low-frequency variants (Minor Allele Frequency (MAF) > 0.5%) decreased while the population diversity of the reference panel increased, but for rare variants (MAF  5%) for the European population could always benefit from the expanding sample size. However, for the Han Chinese population, the accuracy of all imputed variants reached the highest when reference panel contained a fraction of an extra diverse sample (8-21%). In addition, we evaluated the imputation performances in the existing reference panels, such as the Haplotype Reference Consortium (HRC), 1000 Genomes Project Phase 3 and the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE). For the European population, the HRC panel showed the best performance in our analysis. For the Han Chinese population, we proposed an optimum imputation reference panel constituent ratio if researchers would like to customize their own sequenced reference panel, but a high-quality and large-scale Chinese reference panel was still needed. Our findings could be generalized to the other populations with conservative genome; a tool was provided to investigate other populations of interest (https//github.com/Abyss-bai/reference-panel-reconstruction). © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email [email protected] functionalized graphene derivatives were synthetized by a one-pot reaction of fluorographene with organometallic nucleophiles. Their nucleophilicity governed the preference for grafting and was utilized for tuning the functionalization. This approach paves the way toward the facile, up-scalable and controllable multifunctionalization of graphene.Acyl glucuronide metabolites have been implicated in the toxicity of several carboxylic acid-containing drugs, and the rate of their degradation via intramolecular transacylation and hydrolysis has been associated with the degree of protein adduct formation. Although not yet proven, the formation of protein adducts in vivo - and subsequent downstream effects - has been proposed as a mechanism of toxicity for carboxylic acid-containing xenobiotics capable of forming acyl glucuronides. A structurally-related series of metabolites, the acyl glucosides, have also been shown to undergo similar degradation reactions and consequently the potential to display a similar mode of toxicity. Here we report detailed kinetic models of each transacylation and hydrolysis reaction for a series of phenylacetic acid acyl glucuronides and their analogous acyl glucosides. Differences in reactivity were observed for the individual transacylation steps between the compound series; our findings suggest that the charged carboxylate ion and neutral hydroxyl group in the glucuronide and glucoside conjugates, respectively, are responsible for these differences. The transacylation reaction was modelled using density functional theory and the calculated activation energy for this reaction showed a close correlation with the degradation rate of the 1-β anomer. Comparison of optimised geometries between the two series of conjugates revealed differences in hydrogen bonding which may further explain the differences in reactivity observed. Together, these models may find application in drug discovery for prediction of acyl glucuronide and glucoside metabolite behaviour.Variously substituted 2,6-bis(1,1-diarylethyl)anilines and 2,6-bis(trityl)anilines were prepared by a three-step high-yield process. Dimethyl-2-aminoisophtalate was modified by reaction with arylmagnesium bromides, and the hydroxy-derivatives obtained were etherified. Under the non-catalysed C-C coupling protocol, the formed bis[methyl(methoxy)diaryl]anilines react with various Grignard reagents to give highly substituted products. The buried volumes around the central nitrogen atom of the prepared compounds exceed the parameters for the known most sterically hindered anilines by about 20%.New technologies for future electronics such as personal healthcare devices and foldable smartphones require emerging developments in flexible energy storage devices as power sources. Besides the energy and power densities of energy devices, more attention should be paid to safety, reliability, and compatibility within highly integrated systems because they are almost in 24-hour real-time operation close to the human body. Thereupon, all-solid-state energy devices become the most promising candidates to meet these requirements. In this mini-review, the most recent research progress in all-solid-state flexible supercapacitors and batteries will be covered. The main focus of this mini-review is to summarize new materials development for all-solid-state flexible energy devices. The potential issues and perspectives regarding all-solid-state flexible energy device technologies will be highlighted.In this work, we developed multi-shelled hollow nanospheres [RGD@am-ZnO@CuO@Au@DOX HNSs] as multifunctional therapeutic agents to achieve effective and targeted Zn2+/Cu2+ therapy, induced drug delivery under low pH/red-light conditions, and enhanced phototherapy under single red-light. The photothermal and photodynamic performance of am-ZnO@CuO@Au HNSs was enhanced relative to that of am-ZnO nanoparticles (NPs) or am-ZnO@CuO HNSs by utilizing the resonance energy transfer process and broad red-light absorption. The pH-sensitive am-ZnO@CuO@Au HNSs were dissolved to Zn2+/Cu2+ in the acidic endosomes/lysosomes of cancer cells, resulting in a cancer cell killing effect. The release performance of doxorubicin (DOX) from RGD@am-ZnO@CuO@Au@DOX HNSs was evaluated under low pH and red-light-irradiated conditions, and targeting of HNSs was confirmed by dual-modal imaging (magnetic resonance/fluorescence) of the tumor area. Moreover, in vivo synergistic therapy using RGD@am-ZnO@CuO@Au@DOX HNSs was further evaluated in mice bearing human pulmonary adenocarcinoma (A549) cells, achieving a remarkable synergistic antitumor effect superior to that obtained by monotherapy.
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