In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD will discuss the following 6 articles: 1. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC. Activity of selumetinib in neurofibromatosis type 1-related plexiform Neurofibromas. N Engl J Med. 2016;375:2550-2560. 2. Foutz A, Appleby BS, Hamlin C, Liu X, Yang S, Cohen Y, Chen W, Blevins J, Fausett C, Wang H, Gambetti P, Zhang S, Hughson A, Tatsuoka C, Schonberger LB, Cohen ML, Caughey B, Safar JG. Diagnostic and prognostic value of human prion detection in cerebrospinal fluid. Ann Neurol. 2017;81:79-92. 3. Kang E, Wu J, Gutierrez NM, Koski A, Tippner-Hedges R, Agaronyan K, Platero-Luengo A, Martinez-Redondo P, Ma H, Lee Y, Hayama T, Van Dyken C, Wang X, Luo S, Ahmed R, Li Y, Ji D, Kayali R, Cinnioglu C, Olson S, Jensen J, Battaglia D, Lee D, Wu D, Huang T, Wolf DP, Temiakov D, Belmonte JC, Amato P, Mitalipov S. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature. 2016;540:270-275. 4. Cestari DM, Gaier ED, Bouzika P, Blachley TS, De Lott LB, Rizzo JF, Wiggs JL, Kang JH, Pasquale LR, Stein JD. Demographic, systemic, and ocular factors associated with nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2016;123:2446-2455. 5. van der Vuurst de Vries RM, Mescheriakova JY, Runia TF, Jafari N, Siepman TA, Hintzen RQ. Soluble CD27 levels in cerebrospinal fluid as a prognostic biomarker in clinically isolated syndrome. JAMA Neurol. 2017;74:286-292. 6. Lee KM, Woo SJ, Hwang JM. Differentiation between optic disc drusen and optic disc oedema using fundus photography. Acta Ophthalmol. [published ahead of print January 13, 2017] doi: 10.1111/aos.13338. (C) 2017 by North American Neuro-Ophthalmology Society
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Πέμπτη 4 Μαΐου 2017
Neuroimaging "HINTS" of the Lateral Medullary Syndrome.
Exacerbations of oral lichen planus and elevated levels of aminotransferases
Abstract
Background
Liver enzymes appear to be involved in oral lichen planus (OLP), but it is not known whether the elevation develops concomitantly with exacerbations of disease. We compared the levels of serum hepatic aspartate (AST) and alanine (ALT) aminotransferases as markers of OLP exacerbation in patients with chronic hepatitis C from those with chronic liver disorders, seronegative for hepatitis C virus (HCV).
Methods
We studied 71 patients with OLP, (48 HCV seropositive and 23 HCV seronegative with chronic liver diseases) measuring AST and ALT. Association of HCV infection status with serum aminotransferase levels in relation to several types of OLP, exacerbations, and clinical score was studied by means of logistic and linear regression (correcting for age and sex).
Results
Of 476 patients screened, 71 were eligible for the study. Patients in the HCV seropositive group had more elevation of AST and ALT levels (mean level, 51.0 U/l; normal level, <45) than patients in the HCV seronegative group (mean level, 47.5 U/l). Mean serum AST and ALT exceeded the upper limit of the normal range in 33 of 48 (68.8%) in the HCV antibody-positive group and in 9 of 23 (39.5%) in the HCV antibody-negative group. Exacerbations of OLP were more frequent in the high-level AST and ALT group, while HCV status group played a minor role.
Conclusions
Among patients with OLP, mild elevation in aminotransferase levels was more common in patients infected with HCV. AST and ALT concentrations were elevated in association with exacerbation of OLP.
http://ift.tt/2pfr9jO
Identification of students with asthma in Chicago schools
Source:Annals of Allergy, Asthma & Immunology
Author(s): Anna Volerman, Stacy Ignoffo, Ashley Hull, Syrennia McArthur Hanshaw, Susan Taylor, Monica Vela, Valerie G. Press
http://ift.tt/2pLZlEX
Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age
Source:Annals of Allergy, Asthma & Immunology
Author(s): Joy Wan, Nandita Mitra, Ole J. Hoffstad, David J. Margolis
http://ift.tt/2pG4eRk
Predictors of emergency department use in children with persistent asthma in metropolitan Atlanta, Georgia
Publication date: Available online 4 May 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jeffery M. Franklin, Jocelyn R. Grunwell, Alice C. Bruce, Robin C. Smith, Anne M. Fitzpatrick
BackgroundRacial disparities are evident among children with asthma in the United States, with non-Hispanic black children at particularly high risk for poor asthma outcomes, including frequent emergency department (ED) use for asthma exacerbations.ObjectiveTo compare asthma features in non-Hispanic black vs white children in Atlanta, Georgia, and determine what clinical features predict future ED use for asthma.MethodsSelf-reported black and white children 6 to 17 years of age with persistent asthma treated with controller medications completed medical history questionnaires, lung function testing, aeroallergen sensitization testing, and venipuncture. Medical records were reviewed for asthma-related ED visits for 12 months after the initial study visit.ResultsA total of 276 children were enrolled. Black children, compared with white children, resided in more disadvantaged zip code areas and were more likely to have public insurance. Black children also had more features of asthma severity and more ED visits during the study period. Predictors of ED use, aside from a previous ED visit, differed by race. After adjustment for socioeconomic status, predictors of ED use in white children included an ED visit in the previous year and sensitization to pets and dust; in black children, predictors included ED use in the previous year, the number of asthma controller medications, forced expiratory volume in 1 second less than 80% predicted, blood eosinophil count greater than 4%, and mold sensitization.ConclusionAsthma features and ED use differ between black and white children in metropolitan Atlanta. Strategies to eliminate allergen exposure in the home and improve asthma control in these children may require tailoring for different racial groups.
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The impact of the halogen bonding on D2 and 5-HT1A/5-HT7 receptor activity of azinesulfonamides of 4-[(2-ethyl)piperidinyl-1-yl]phenylpiperazines with antipsychotic and antidepressant properties
Publication date: Available online 4 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Anna Partyka, Rafał Kurczab, Vittorio Canale, Grzegorz Satała, Krzysztof Marciniec, Agnieszka Pasierb, Magdalena Jastrzębska-Więsek, Maciej Pawłowski, Anna Wesołowska, Andrzej J Bojarski, Paweł Zajdel
A series of azinesulfonamides of long-chain arylpiperazine derivatives with semi-rigid alkylene spacer was designed, synthesized, and biologically evaluated using in vitro methods for their affinity for dopaminergic D2 and serotoninergic 5-HT1A, 5-HT2A, 5-HT6 and 5-HT7 receptors. Docking to homology models revealed a possible halogen bond formation in complexes of the most potent ligands and the target receptors. The study allowed for the identification of compound 5-({4-(2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl)piperidin-1-yl}sulfonyl)quinoline (21), which behaved as D2, 5-HT1A and 5-HT7 receptor antagonist. In preliminary in vivo studies, compound 21 displayed distinct antipsychotic properties in the MK-801-evoked hyperactivity test in mice at a dose of 10 mg/kg, and exerted antidepressant-like effect in a forced swim test in mice (MED=0.625 mg/kg, i.p.).
Graphical abstract
http://ift.tt/2pM82z6
Dual functional small molecule fluorescent probes for image-guided estrogen receptor-specific targeting coupled potent antiproliferative potency for breast cancer therapy
Publication date: Available online 4 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Lu Yang, Zhiye Hu, Junjie Luo, Chu Tang, Silong Zhang, Wentao Ning, Chune Dong, Jian Huang, Xianjun Liu, Hai-Bing Zhou
A strategy by integrating biological imaging into early stages of the drug discovery process can improve our understanding of drug activity during preclinical and clinical study. In this article, we designed and synthesized coumarin-based nonsteroidal type fluorescence ligands for drug-target binding imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER binding affinity and 3e (IC50 = 0.012 μM) exhibited excellent ERα antagonistic activity, its antiproliferative potency in breast cancer MCF-7 cells is equipotent to the approved drug tamoxifen. The fluorescence of compounds 3e and 3f depended on the solvent properties and showed significant changes when mixed with ERα and ERβ in vitro. Furthermore, target molecule 3e could cross the cell membrane, localize and image drug-target interaction in real time without cell washing. Thus, the coumarin-based platform represents a promising new ER-targeted delivery vehicle with potential imaging and therapeutic properties
Graphical abstract
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Synthesis and biological research of novel azaacridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors
Publication date: Available online 4 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Dan Li, Zigao Yuan, Shaopeng Chen, Cunlong Zhang, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA and DNA-related enzymes are one of the most effective and common used intracellular anticancer targets in clinic and laboratory studies, however, most of DNA-targeting drugs suffered from toxic side effects. Development of new molecules with good antitumor activity and low side effects is important. Based on computer aided design and our previous studies, a series of novel azaacridine derivatives were synthesized as DNA and topoisomerases binding agents, among which compound 9 displayed the best antiproliferative activity with an IC50 value of 0.57 μM against U937 cells, which was slightly better than m-AMSA. In addition, compound 9 displayed low cytotoxicity against human normal liver cells (QSG-7701), the IC50 of which was more than 3 times lower than m-AMSA. Later study indicated that all the compounds displayed topoisomerases II inhibition activity at 50 μM. The representative compound 9 could bind with DNA and induce U937 apoptosis through the exogenous pathway.
Graphical abstract
http://ift.tt/2pMoOOr
Click strategy using disodium salts of amino acids improves the water solubility of plinabulin and KPU-300
Publication date: Available online 4 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Fumika Yakushiji, Kyohei Muguruma, Yoshiki Hayashi, Takuya Shirasaka, Ryosuke Kawamata, Hironari Tanaka, Yushi Yoshiwaka, Akihiro Taguchi, Kentaro Takayama, Yoshio Hayashi
Plinabulin and KPU-300 are promising anti-microtubule agents; however, the low water solubility of these compounds (<0.1 µg/mL) has limited their pharmaceutical advantages. Here, we developed five water-soluble derivatives of plinabulin and KPU-300 with a click strategy using disodium salts of amino acids. The mother skeleton, diketopiperazine (DKP), was transformed into a monolactim-type alkyne and a copper-catalyzed alkyne azide cycloaddition (CuAAC) combined azides that was derived from amino acids as a water-solubilizing moiety. The conversion of carboxyl groups into disodium salts greatly improved the water solubility by 0.8 million times compared to the solubility of the parent molecules. In addition, the α–amino acid side chains of the water-solubilizing moieties affected both the water solubility and the half-lives of the compounds during enzymatic hydrolysis. Our effort to develop a variety of water-soluble derivatives using the click strategy has revealed that the replaceable water-solubilizing moieties can alter molecular solubility and stability under enzymatic hydrolysis. With this flexibility, we are approaching to the in vivo study using water-soluble derivative
Graphical abstract
http://ift.tt/2pM4Inz
Kinetic properties and affinities for sulfonamide inhibitors of an α-carbonic anhydrase (CruCA4) involved in coral biomineralization in the Mediterranean red coral Corallium rubrum
Publication date: Available online 3 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sonia Del Prete, Daniela Vullo, Didier Zoccola, Sylvie Tambutté, Clemente Capasso, Claudiu T. Supuran
We report the kinetic properties and sulfonamide inhibition profile of an α-carbonic anhydrase (CA, EC 4.2.1.1), named CruCA4, identified in the red coral Corallium rubrum. This isoform is involved in the biomineralization process leading to the formation of a calcium carbonate skeleton. Experiments performed on the recombinant protein show that the enzyme has a "moderate activity" level. Our results are discussed compared to values obtained for other CA isoforms involved in biomineralization. This is the first study describing the biochemical characterization of an octocoral CA.
Graphical abstract
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Discovery of indolin-2-one derivatives as potent PAK4 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
Publication date: Available online 3 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jing Guo, Mingyue Zhu, Tianxiao Wu, Chenzhou Hao, Kai Wang, Zizheng Yan, Wanxu Huang, Jian Wang, Dongmei Zhao, Maosheng Cheng
Utilizing a pharmacophore hybridization approach, a novel series of substituted indolin-2-one derivatives were designed, synthesized and evaluated for their in vitro biological activities against p21-activated kinase 4. Compounds 11b, 12d and 12g exhibited the most potent inhibitory activity against PAK4 (IC50 = 22 nM, 16 nM and 27 nM, respectively). Among them, compound 12g showed the highest antiproliferative activity against A549 cells (IC50 = 0.83 μM). Apoptosis analysis in A549 cells suggested that compound 12g delayed cell cycle progression by arresting cells in the G2/M phase of the cell cycle, retarding cell growth. Further investigation demonstrated that compound 12g strongly inhibited migration and invasion of A549 cells. Western blot analysis indicated that compound 12g potently inhibited the PAK4/LIMK1/cofilin signalling pathways. Finally, the binding mode between compound 12g with PAK4 was proposed by molecular docking. A preliminary ADME profile of the compound 12g was also drawn on the basis of QikProp predictions.
Graphical abstract
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Effect of Water-Extractable Arabinoxylans from Wheat Aleurone and Bran on Lipid Peroxidation and Factors Influencing their Antioxidant Capacity
Publication date: Available online 4 May 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Lovemore Nkhata Malunga, Marta Izydorczyk, Trust Beta
Dietary lipid hydroperoxides (LOOH) are implicated in the rise of colon cancers. We investigated the effect of water-extractable arabinoxylans (WEAX) on lipid peroxidation under simulated gastric conditions. Water-extractable fractions containing mostly arabinoxylans were isolated from wheat aleurone and wheat bran and fractionated by stepwise precipitation with (NH4)2SO4 at 50 and 75% saturation. LOOH concentration (121.2 ± 3.8µM/g) of grilled chicken breast muscle increased by 30%; however, it remained unaltered or decreased (≤35%) depending on type and concentration of WEAX fractions. Antioxidant capacity of WEAX fractions based on DPPH, ABTS and ORAC was 28.2 – 147.9, 91.2 – 355.3, and 185.9 – 527.5µM TE/g, respectively. The content of ferulic acid residues in WEAX fractions (R = 0.99) and relative proportions of monosubstituted xylose residues (R = 0.80) influenced the antioxidant capacity. Consumption of diets rich in feruloylated WEAX may offer protection against oxidative damage in the gastrointestinal tract.
http://ift.tt/2q5n465
Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei
Source:Molecular and Cellular Endocrinology
Author(s): Gisela Paola Lazzarino, María Florencia Andreoli, María Florencia Rossetti, Cora Stoker, María Virgina Tschopp, Enrique Hugo Luque, Jorge Guillermo Ramos
We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity.
http://ift.tt/2pMv76I
Estrogen receptor-related receptor γ regulates testicular steroidogenesis through direct and indirect regulation of steroidogenic gene expression
Source:Molecular and Cellular Endocrinology
Author(s): Eunsook Park, Sudeep Kumar, Bobae Lee, Kyung-Jin Kim, Jeong-Eun Seo, Hueng-Sik Choi, Keesook Lee
Biosynthesis of testosterone, which mainly occurs in testicular Leydig cells, is controlled by steroidogenic proteins, such as StAR and P450c17. Although estrogen-related receptor gamma (ERRγ), an orphan nuclear receptor, is expressed in the testis, its role is not well understood. In this study, we investigated the expression of ERRγ in Leydig cells and its molecular action on testicular steroidogenesis. ERRγ is expressed in mouse Leydig cells from pre-pubertal stages. ERRγ overexpression in primary Leydig cells elevated the production of testosterone with a marked increase of P450c17 expression at both mRNA and protein levels, albeit decreased expression of StAR. Promoter-reporter analyses showed that ERRγ directly regulated the P450c17 promoter. Further deletion mutant analyses of the P450c17 promoter revealed that ERRγ activated expression of the P450c17 gene by binding to an ERRγ response element within the P450c17 promoter. Meanwhile, ERRγ suppressed cAMP-induced activation of the StAR promoter, which was likely due to ERRγ-mediated inhibition of the transcriptional activity of Nur77, which is induced by cAMP and regulates StAR gene expression in Leydig cells. Interestingly, ERRγ coexpression also decreased the protein level of Nur77, which occurred through proteasomal degradation, suggesting ERRγ-mediated regulation of steroidogenesis at another level. Taken together, these findings suggest that ERRγ regulates testicular steroidogenesis, both directly controlling and indirectly fine-tuning the expression of steroidogenic genes.
http://ift.tt/2pLWvj6
Characterization of synthetic ecdysteroid analogues as functional mimics of brassinosteroids in plant growth
Publication date: Available online 4 May 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Jutiporn Thussagunpanit, Kanapol Jutamanee, Sureeporn Homvisasevongsa, Apichart Suksamrarn, Ayumi Yamagami, Takeshi Nakano, Tadao Asami
Brassinosteroids (BRs) are plant steroidal hormones that play important roles in many stages of plant growth. Several plant species produce ecdysteroids, which are known as insect molting steroid hormones. In this study, we evaluated the biological activities of three hydroxysteroidal compounds, 20-hydroxyecdysone (ECD), 7,8-dihydro-8α-20-hydroxyecdysone (DHECD), and 7,8-dihydro-5a,8a-20-hydroxyecdysone (a-DHECD), and compared their activities with that of brassinolide (BL), the most potent BR. In rice, DHECD and a-DHECD enhanced the degree of lamina inclination, as do BRs. In Arabidopsis thaliana, DHECD and a-DHECD increased hypocotyl length in the wild-type, and also partially overcame the hypocotyl shortening in the wild-type caused by 0.3μM brassinazole, a specific BR biosynthesis inhibitor. DHECD and a-DHECD partially reduced dwarfism in the BR-biosynthesis-deficient mutant det2. Treatment with DHECD or a-DHECD downregulated the expression of the BR biosynthesis genes DWF4 and CPD, which are generally, suppressed by BR, and upregulated the expression of TCH4 and SAUR-AC1, which are generally promoted by BR. However, their regulated activities were less effective than BL. Moreover, the 10−4M DHECD and a-DHECD induced the accumulation of dephosphorylated BIL1/BZR1 that enhanced BR signaling as a master transcription factor. In contrast, ECD did not affect rice lamina bending, Arabidopsis hypocotyl elongation, the expression levels of BR-related genes and BIL1/BZR1 phosphorylation status. Based on these results, we hypothesize that both DHECD and a-DHECD have functional activities similar to those of BR.
http://ift.tt/2pMCzi3
Design strategies of oxidosqualene cyclase inhibitors: targeting the sterol biosynthetic pathway
Publication date: Available online 4 May 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Vitor Won-Held Rabelo, Nelilma Correia Romeiro, Paula Alvarez Abreu
Targeting the sterol biosynthesis pathway has been explored for the development of new bioactive compounds. Among the enzymes of this pathway, oxidosqualene cyclase (OSC) which catalyzes lanosterol cyclization from 2,3-oxidosqualene has emerged as an attractive target. In this work, we reviewed the most promising OSC inhibitors from different organisms and their potential for the development of new antiparasitic, antifungal, hypocholesterolemic and anticancer drugs. Different strategies have been adopted for the discovery of new OSC inhibitors, such as structural modifications of the natural substrate or the reaction intermediates, the use of the enzyme's structural information to discover compounds with novel chemotypes, modifications of known inhibitors and the use of molecular modeling techniques such as docking and virtual screening to search for new inhibitors. This review brings new perspectives on structural insights of OSC from different organisms and reveals the broad structural diversity of OSC inhibitors which may help evidence lead compounds for further investigations with various therapeutic applications.
http://ift.tt/2pM7KbD
Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: a comparative study with 17β-estradiol
Publication date: Available online 4 May 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Teresa Jover-Mengual, María Castelló-Ruiz, María C. Burguete, María Jorques, Mikahela A. López-Morales, Alicia Aliena-Valero, Andrés Jurado-Rodríguez, Salvador Pérez, José M. Centeno, Francisco J. Miranda, Enrique Alborch, Germán Torregrosa, Juan B. Salom
As the knowledge on the estrogenic system in the brain grows, the possibilities to modulate it in order to afford further neuroprotection in brain damaging disorders so do it. We have previously demonstrated the ability of the selective estrogen receptor modulator, bazedoxifene (BZA), to reduce experimental ischemic brain damage. The present study has been designed to gain insight into the molecular mechanisms involved in such a neuroprotective action by investigating: 1) stroke-induced apoptotic cell death; 2) expression of estrogen receptors (ER) ERα, ERβ and the G-protein coupled estrogen receptor (GPER); and 3) modulation of MAPK/ERK1/2 and PI3K/Akt signaling pathways. For comparison, a parallel study was done with 17β-estradiol (E2)-treated animals. Male Wistar rats subject to transient right middle cerebral artery occlusion (tMCAO, intraluminal thread technique, 60min), were distributed in vehicle-, BZA- (20.7±2.1ng/mL in plasma) and E2- (45.6±7.8pg/mL in plasma) treated groups. At 24h from the onset of tMCAO, RT-PCR, Western blot and histochemical analysis were performed on brain tissue samples. Ischemia-reperfusion per se increased apoptosis as assessed by both caspase-3 activity and TUNEL-positive cell counts, which were reversed by both BZA and E2. ERα and ERβ expression, but not that of GPER, was reduced by the ischemic insult. BZA and E2 had different effects: while BZA increased both ERα and ERβ expression, E2 increased ERα expression but did not change that of ERβ. Both MAPK/ERK1/2 and PI3K/Akt pathways were stimulated under ischemic conditions. While BZA strongly reduced the increased p-ERK1/2 levels, E2 did not. Neither BZA nor E2 modified ischemia-induced increase in p-Akt levels. These results show that modulation of ERα and ERβ expression, as well as of the ERK1/2 signaling pathway accounts, at least in part, for the inhibitory effect of BZA on the stroke-induced apoptotic cell death. This lends mechanistic support to the consideration of BZA as a potential neuroprotective drug in acute ischemic stroke treatment.
http://ift.tt/2pMRiK2
Corrigendum to “Development of SERS substrate using phage-based magnetic template for triplex assay in sepsis diagnosis” [Biosens. Bioelectron. 85 (2016) 522–528]
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Anh H. Nguyen, Yesol Shin, Sang Jun Sim
http://ift.tt/2pLUPpY
Metal ion detection using functional nucleic acids and nanomaterials
Source:Biosensors and Bioelectronics, Volume 96
Author(s): Jiahao Huang, Xuefen Su, Zhigang Li
Metal ion detection is critical in a variety of areas. The past decade has witnessed great progress in the development of metal ion sensors using functional nucleic acids (FNAs) and nanomaterials. The former has good recognition selectivity toward metal ions and the latter possesses unique properties for enhancing the performance of metal ion sensors. This review offers a summary of FNA- and nanomaterial-based metal ion detection methods. FNAs mainly include DNAzymes, G-quadruplexes, and mismatched base pairs and nanomaterials cover gold nanoparticles (GNPs), quantum dots (QDs), carbon nanotubes (CNTs), and graphene oxide (GO). The roles of FNAs and nanomaterials are introduced first. Then, various methods based on the combination of different FNAs and nanomaterials are discussed. Finally, the challenges and future directions of metal ion sensors are presented.
http://ift.tt/2pFudsn
Editorial Board
Source:Biosensors and Bioelectronics, Volume 95
http://ift.tt/2pFjONo
Demographics and clinical features predictive of allergic versus non-allergic rhinitis in children aged 6–18 years: A single-center experience of 1535 patients
Chronic rhinitis (CR) is one of the most common causes accounting for lost-school days, absenteeism and resource utilization in pediatric patients. Distinction between common causes of CR, allergic (AR)and non-allergic rhinitis (NAR), based upon clinical features is critical, especially in primary care settings or facilities with lack of allergen sensitivity testing, as management strategies differ considerably. The current study elucidates clinical factors, particularly facial features associated with AR and NAR using a large cohort.
http://ift.tt/2pLNyqj
Biocompatibility and neurotoxicity of magnesium alloys potentially used for neural repairs
Publication date: 1 September 2017
Source:Materials Science and Engineering: C, Volume 78
Author(s): Jianjun Fei, Xiaoxiao Wen, Xiao Lin, Saijilafu, Weihua Wang, Olga Ren, Xinjian Chen, Lili Tan, Ke Yang, Huilin Yang, Lei Yang
Nerve injury, especially the large-size nerve damage, is a serious problem affecting millions of people. Entubulation of two ends of the injured nerve by using an implantable device, e.g., nerve guidance conduit (NGC), to guide the regeneration of nerve tissue is a promising approach for treating the large-size nerve defect. Magnesium (Mg) and its alloys are biodegradable, conductive, and own good mechanical properties. Mg2+ ion, one of the main degradation products of Mg and its alloys, was reported to promote the proliferation of neural stem cells and their neurite production. Thus, Mg and its alloys are potential materials for fabricating the nerve repair implants, such as NGC or scaffold. However, the compatibility of Mg alloys to cells, especially neurons is not clear. In this work, NZ20 (Mg-2Nd-Zn), ZN20 (Mg-2Zn-Nd) and Mg-10Li magnesium alloys were selected for study, due to the improved mechanical properties of NZ20 and ZN20 alloys and bio-function of Li+ ions from Mg-10Li to nervous system, respectively. The degradation behavior and biocompatibility were studied by in vitro degradation test and cell adhesion assay, respectively. Specifically, the cytocompatibility to dorsal root ganglion (DRG) neurons, RF/6A choroid-retina endothelial cells, and osteoblasts in the cell culture media containing Mg alloy extracts were investigated. The results showed that Mg alloys degraded at different rates in cell culture media and artificial cerebrospinal fluid. The three alloy extracts showed negligible toxic effects on the endothelial cells and osteoblasts at short term (1 day), while NZ20 extract inhibited the proliferation of these two types of cells. The effect of Mg alloy extracts on cell proliferation was also concentration-dependent. For DRG neurons, ZN20 and Mg-10Li alloy extracts showed no neural toxicity compared with control group. The results of the present work show a potential and feasibility of Mg-10Li and ZN20 for nerve repair applications.
http://ift.tt/2q5e6pq
Human health risks related to the consumption of foodstuffs of plant and animal origin produced on a site polluted by chemical munitions of the First World War
Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 599–600
Author(s): Sébastien Gorecki, Fabrice Nesslany, Daniel Hubé, Jean-Ulrich Mullot, Paule Vasseur, Eric Marchioni, Valérie Camel, Laurent Noël, Bruno Le Bizec, Thierry Guérin, Cyril Feidt, Xavier Archer, Aurélie Mahe, Gilles Rivière
Shells fired during World War I exhibited different explosive compounds and some of these weapons also contained a wide variety of chemical warfare agents. At the end of the war, for safety purposes, the large quantity of weapons remaining on the former front needed to be dismantled and destroyed. A large amount of the remaining shells was destroyed in specific sites which led to the contamination of the surroundings in Belgium and France.In the 1920s, 1.5 million chemical shells and 30,000 explosive shells were destroyed in a place close to the city of Verdun, in the East of France. In this paper, the risk for human health related to the consumption of foodstuffs produced on this site was assessed. To this end, food products of plant and animal origin were sampled in 2015–2016 and contaminant analyses were conducted. Human exposure was assessed using a specifically built methodology. The contaminants considered in this study were trace elements (TEs - primarily Zn, As, Pb and Cd), nitroaromatic explosives (trinitrotoluene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2-amino-4,6-dinitroluene and 4-amino-2,6-dinitrotoluene), phenylarsenic compounds including diphenylarsinic acid and triphenylarsine, perchlorate, tetrabromoethane and vinyl bromide. Depending on the compound, different approaches were used to assess the risk for both adults and children.Exposure to these contaminants through the consumption of foodstuffs produced locally on the considered site was unlikely to be a health concern. However, as for inorganic arsenic, given the presence of highly contaminated zones, it was suggested that cereals should not be grown on certain plots.
Graphical abstract
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Epiglottitis as the Presenting Sign of Mucous Membranous Pemphigoid: A Case Report
Mucous membranous pemphigoid (MMP) is an autoimmune disease of the mucous membranes characterized by formation of subepithelial blisters. MMP commonly involves the ocular and oral mucosa. Laryngeal MMP is very rare, estimated as occurring in 1 of 10 million persons in the general population. It mostly affects the supraglottis, but may also involve other laryngeal sites as well as extralaryngeal areas. This report describes the clinical picture, workup to diagnosis, and differential diagnosis of an isolated epiglottic process in an elderly female who presented with isolated, long-standing, nonresolving epiglottitis, later diagnosed as MMP with epiglottal and oral involvement.
http://ift.tt/2qx8Zyc
Consonant Acquisition in Young Cochlear Implant Recipients and Their Typically Developing Peers
Purpose
Consonant acquisition was examined in 13 young cochlear implant (CI) recipients and 11 typically developing (TD) children. Method
A longitudinal research design was implemented to determine the rate and nature of consonant acquisition during the first 2 years of robust hearing experience. Twenty-minute adult–child (typically a parent) interactions were video and audio recorded at 3-month intervals following implantation until 24 months of robust hearing experience was achieved. TD children were similarly recorded between 6 and 24 months of age. Consonants that were produced twice within a 50-utterance sample were considered "established" within a child's consonant inventory. Results
Although the groups showed similar trajectories, the CI group produced larger consonant inventories than the TD group at each interval except for 21 and 24 months. A majority of children with CIs also showed more rapid acquisition of consonants and more diverse consonant inventories than TD children. Conclusions
These results suggest that early auditory deprivation does not significantly affect consonant acquisition for most CI recipients. Tracking early consonant development appears to be a useful way to assess the effectiveness of cochlear implantation in young recipients.http://ift.tt/2qKDJYQ
Developing the Alphabetic Principle to Aid Text-Based Augmentative and Alternative Communication Use by Adults With Low Speech Intelligibility and Intellectual Disabilities
Purpose
We explored alphabet supplementation as an augmentative and alternative communication strategy for adults with minimal literacy. Study 1's goal was to teach onset-letter selection with spoken words and assess generalization to untaught words, demonstrating the alphabetic principle. Study 2 incorporated alphabet supplementation within a naming task and then assessed effects on speech intelligibility. Method
Three men with intellectual disabilities (ID) and low speech intelligibility participated. Study 1 used a multiple-probe design, across three 20-word sets, to show that our computer-based training improved onset-letter selection. We also probed generalization to untrained words. Study 2 taught onset-letter selection for 30 new words chosen for functionality. Five listeners transcribed speech samples of the 30 words in 2 conditions: speech only and speech with alphabet supplementation. Results
Across studies 1 and 2, participants demonstrated onset-letter selection for at least 90 words. Study 1 showed evidence of the alphabetic principle for some but not all word sets. In study 2, participants readily used alphabet supplementation, enabling listeners to understand twice as many words. Conclusions
This is the first demonstration of alphabet supplementation in individuals with ID and minimal literacy. The large number of words learned holds promise both for improving communication and providing a foundation for improved literacy.http://ift.tt/2qxseHQ
Short sleep duration is associated with B-type natriuretic peptide levels and predicts the death of Japanese patients with type 2 diabetes
To investigate the associations of sleep duration with all-cause mortality, glycemic control, and other clinical parameters of patients with type 2 diabetes.
http://ift.tt/2pFADaO
Theoretical basis, application, reliability, and sample size estimates of a Meridian Energy Analysis Device for Traditional Chinese Medicine Research
OBJECTIVES: The Meridian Energy Analysis Device is currently a popular tool in the scientific research of meridian electrophysiology. In this field, it is generally believed that measuring the electrical conductivity of meridians provides information about the balance of bioenergy or Qi-blood in the body. METHODS AND RESULTS: PubMed database based on some original articles from 1956 to 2014 and the authoŕs clinical experience. In this short communication, we provide clinical examples of Meridian Energy Analysis Device application, especially in the field of traditional Chinese medicine, discuss the reliability of the measurements, and put the values obtained into context by considering items of considerable variability and by estimating sample size. CONCLUSION: The Meridian Energy Analysis Device is making a valuable contribution to the diagnosis of Qi-blood dysfunction. It can be assessed from short-term and long-term meridian bioenergy recordings. It is one of the few methods that allow outpatient traditional Chinese medicine diagnosis, monitoring the progress, therapeutic effect and evaluation of patient prognosis. The holistic approaches underlying the practice of traditional Chinese medicine and new trends in modern medicine toward the use of objective instruments require in-depth knowledge of the mechanisms of meridian energy, and the Meridian Energy Analysis Device can feasibly be used for understanding and interpreting traditional Chinese medicine theory, especially in view of its expansion in Western countries.
http://ift.tt/2pLTXS2
Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma
OBJECTIVES: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.
http://ift.tt/2pFwdRj
Effects of Motor Learning on Clinical Isokinetic Test Performance in Knee Osteoarthritis Patients
OBJECTIVES: To analyze the effects of motor learning on knee extension-flexion isokinetic performance in knee osteoarthritis patients. METHODS: One hundred and thirty-six middle-aged and older sedentary individuals (111 women, 64.3±9.9 years) with knee osteoarthritis (130 patients with bilateral) and who had never performed isokinetic testing underwent two bilateral knee extension-flexion (concentric-concentric) isokinetic evaluations (5 repetitions) at 60°/sec. The tests were first performed on the dominant leg with 2 min of recovery between test, and following a standardized warm-up that included 3 submaximal isokinetic repetitions. The same procedure was repeated on the non-dominant leg. The peak torque, peak torque adjusted for the body weight, total work, coefficient of variation and agonist/antagonist ratio were compared between tests. RESULTS: Patients showed significant improvements in test 2 compared to test 1, including higher levels of peak torque, peak torque adjusted for body weight and total work, as well as lower coefficients of variation. The agonist/antagonist relationship did not significantly change between tests. No significant differences were found between the right and left legs for all variables. CONCLUSION: The results suggest that performing two tests with a short recovery (2 min) between them could be used to reduce motor learning effects on clinical isokinetic testing of the knee joint in knee osteoarthritis patients.
http://ift.tt/2pLTKOW
Does aortic valve repair in valve-sparing aortic root reconstruction compromise the longevity of the procedure?
OBJECTIVES: The effect of performing aortic valve repair in combination with valve-sparing operation on the length of time for which patients are free from reoperation is unclear. The objective of this study was to determine if the performance of aortic valve repair during valve-sparing operation modified the freedom from reoperation time. METHODS: From January 2003 to July 2014, 78 patients with a mean age of 49±15 years underwent valve-sparing operation. Sixty-eight percent of these patients were male. Twenty-two (28%) aortic valve repair procedures were performed in this patient population. In the aortic valve repair + valve-sparing operation group, 77.3% of patients had moderate/severe aortic insufficiency, while in the valve-sparing operation group, 58.6% of patients had moderate/severe aortic insufficiency (ns = not significant). Additionally, 13.6% of patients in the aortic valve repair + valve-sparing operation group had functional class III/IV, while 14.2% of patients in the valve-sparing operation group had functional class III/IV (ns). RESULTS: The in-hospital and late mortality rates, for the aortic valve repair + valve-sparing operation and valve-sparing operation groups were similar, as they were 4.5% and 3.6%; and 0% and 1.8%, respectively. In the aortic valve repair + valve-sparing operation group, 0% of patients presented moderate/severe aortic insufficiency during late follow-up, while in the valve-sparing operation group, 14.2% of patients presented with moderate/severe aortic insufficiency during this period (ns). In the aortic valve repair + valve-sparing operation group, 5.3% of patients presented with functional class III/IV, while in the valve-sparing operation group, 4.2% of patients presented with functional class III/IV (ns). In the aortic valve repair + valve-sparing operation group, 0% of patients required reoperation, while in the valve-sparing operation group, 3.6% of patients required reoperation over a mean follow-up period of 1621±1156 days (75 patients). CONCLUSION: Valve-sparing operation is a safe and long-lasting procedure and performance of aortic valve repair when necessary does not increase risk of reoperation on the aortic valve.
http://ift.tt/2pFs7sg
Association between language and hearing disorders – risk identification
OBJECTIVE: To identify children at risk for hearing and/or language disorders and to investigate the association between these risks by conducting pre-validated hearing and language screenings. METHODS: The study was conducted during a polio vaccination campaign in August of 2013 in basic health units in western São Paulo. Parents of children between 2 and 5 years of age were asked to complete two screening tools: a hearing questionnaire (regarding hearing development) and a language production and comprehension scale (including the major language development milestones). The screening tools were administered by different researchers. We compared the risk of having language disorders among children at risk for hearing loss versus children not at risk, as well as the attributable risk and odds ratios. Chi-squared tests and logistic regression analyses were used. RESULTS: The study included 479 children with a mean age of three and one-half years, of whom 26.9% were identified as at risk for deficits in language production, 8.6% were at risk for deficits in language comprehension and 14% were at risk for hearing disorders. The children at risk for hearing disorders were twice as likely as those not at risk to exhibit language production and comprehension deficits. CONCLUSION: The results of this study highlight the importance of establishing and adopting low-cost procedures such as screenings to identify children at risk of developing language and/or hearing disorders in early childhood.
http://ift.tt/2pLVec5
Treatment of acromegaly patients at the Federal University of Triângulo Mineiro (UFTM): Experience Report
OBJECTIVE: To evaluate the effectiveness of the treatment of acromegaly patients at the Federal University of Triangulo Mineiro. METHODS: Cross-sectional and retrospective study of thirty cases treated over a period of two decades. RESULTS: 17 men (56.7%) aged 14-67 years and 13 women aged 14-86 years were analyzed. Twenty-one patients underwent transphenoidal surgery, whichwas associated with somatostatin receptor ligands in 11 patients (39.3%), somatostatin receptor ligands + radiotherapyin 5 patients (17.8%), radiotherapy in 3 patients (10.7%), and radiotherapy + somatostatin receptorligands + cabergoline in 1 patient (3.6%). Additionally, 2 patients underwent radiotherapy and surgeryalone. Six patients received somatostatin receptor ligands before surgery, and 2 were not treated due to refusal and death. Nine patients have died, and 20 are being followed; 13 (65%) have growth hormonelevels o1 ng/mL, and 11 have normal insulin-like growth factor 1 levels. CONCLUSION: The current treatment options enable patients seen in regional reference centers to achieve strict control parameters, which allows them to be treated close to their homes.
http://ift.tt/2pFsBPl
Insulin resistance and associated factors: a cross-sectional study of bank employees
OBJECTIVE: Insulin resistance is characterized by the failure of target cells to respond to normal levels of circulating insulin, and this condition is related to cardiovascular disease. This study sought to evaluate the prevalence of insulin resistance and its association with markers of metabolic abnormalities and metabolic syndrome in bank employees. METHODS: A cross-sectional study was performed on 498 working men and women aged ≥20 years old. The Homeostasis Model Assessment (HOMA-IR) was used to determine the presence of insulin resistance based on cut-off values of ≤2.71 for normal insulin levels and >2.71 for insulin resistance, as established for the adult Brazilian population. RESULTS: It was observed that the 52 (10.4%) overweight individuals with insulin resistance were 4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the normal-weight participants; among those who were obese, the likelihood increased to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were 3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than those who were within normal parameters. The HOMA-IR values differed between subjects with and without metabolic syndrome, with values of 2.83±2.5 and 1.10±0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C-reactive protein and uric acid were also associated with insulin resistance. CONCLUSION: The prevalence of insulin resistance among bank employees is high, and insulin resistance is associated with and serves as a marker of metabolic syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic abnormalities were observed, and insulin resistance may be a risk factor in this group of professionals.
http://ift.tt/2pLP37G
Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment
OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.
http://ift.tt/2pFBs3l
Human islet xenotransplantation in rodents: A literature review of experimental model trends
Among the innovations for the treatment of type 1 diabetes, islet transplantation is a less invasive method of treatment, although it is still in development. One of the greatest barriers to this technique is the low number of pancreas donors and the low number of pancreases that are available for transplantation. Rodent models have been chosen in most studies of islet rejection and type 1 diabetes prevention to evaluate the quality and function of isolated human islets and to identify alternative solutions to the problem of islet scarcity. The purpose of this study is to conduct a review of islet xenotransplantation experiments from humans to rodents, to organize and analyze the parameters of these experiments, to describe trends in experimental modeling and to assess the viability of this procedure. In this study, we reviewed recently published research regarding islet xenotransplantation from humans to rodents, and we summarized the findings and organized the relevant data. The included studies were recent reports that involved xenotransplantation using human islets in a rodent model. We excluded the studies that related to isotransplantation, autotransplantation and allotransplantation. A total of 34 studies that related to xenotransplantation were selected for review based on their relevance and current data. Advances in the use of different graft sites may overcome autoimmunity and rejection after transplantation, which may solve the problem of the scarcity of islet donors in patients with type 1 diabetes.
http://ift.tt/2pLUELn
Breast cancer screening in developing countries
Developing countries have limited healthcare resources and use different strategies to diagnose breast cancer. Most of the population depends on the public healthcare system, which affects the diagnosis of the tumor. Thus, the indicators observed in developed countries cannot be directly compared with those observed in developing countries because the healthcare infrastructures in developing countries are deficient. The aim of this study was to evaluate breast cancer screening strategies and indicators in developing countries. A systematic review and the Population, Intervention, Comparison, Outcomes, Timing, and Setting methodology were performed to identify possible indicators of presentation at diagnosis and the methodologies used in developing countries. We searched PubMed for the terms "Breast Cancer" or "Breast Cancer Screening" and "Developing Country" or "Developing Countries". In all, 1,149 articles were identified. Of these articles, 45 full articles were selected, which allowed us to identify indicators related to epidemiology, diagnostic intervention (diagnostic strategy, diagnostic infrastructure, percentage of women undergoing mammography), quality of intervention (presentation of symptoms at diagnosis, time to diagnosis, early stage disease), comparisons (trend curves, subpopulations at risk) and survival among different countries. The identification of these indicators will improve the reporting of methodologies used in developing countries and will allow us to evaluate improvements in public health related to breast cancer.
http://ift.tt/2pFuUBH
Allergen-specific IgG antibodies signaling via FcγRIIb promote food tolerance
IgG:FcγRIIb ligation restrains allergic pathology and provides a handle for tolerance restoration in food allergy.
http://ift.tt/2pbENnw
A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma
As asthma is a disease that results from host x environment interactions, an approach which allows assessment of the impact of the environment on the host is needed to understand disease. Metabolomics has appealing potential as an application to study pathways to childhood asthma development. The objective of this review is to provide an overview of metabolomics methods, and their application to understanding host x environment pathways in asthma development. We reviewed recent literature on advances in metabolomics and their application to study pathways to childhood asthma development.
http://ift.tt/2qxyv64
Inflammatory phenotypes in severe asthma are associated with distinct airway microbiology
Utilizing a large, well-defined severe asthma cohort, we show that sputum neutrophilia, but not eosinophilia, was a strong predictor for airway microbiota diversity. These results highlight the divergence in pathophysiology based on asthma inflammatory phenotype.
http://ift.tt/2qxmTAj
Glycans and Glycan-specific IgE in Clinical and Molecular Allergology - Sensitization, Diagnostics and Clinical Symptoms
Glycan-specific IgE antibodies are cross-reacting with highly similar or even identical carbohydrate structures on a variety of different natural allergens, the so-called cross-reactive carbohydrate determinants (CCDs). In clinical practice, CCDs often interfere with the specificity of in vitro allergy diagnostics, thus impairing allergy therapy decisions for individual patients. Strikingly, these IgE antibodies directed against CCD often do not cause clinically relevant allergy symptoms. Opposed to that, the IgE-binding glycan allergen galactose-α-(1,3)-galactose (α-Gal) is associated with IgE-mediated delayed anaphylaxis in meat allergy.
http://ift.tt/2pbMFVR
Forkhead Box Protein 3 (FoxP3) Demethylation is Associated with Tolerance Induction in Peanut-Induced Intestinal Allergy
FoxP3+ T regulatory cells are significantly decreased in the jejunum and mesenteric lymph nodes following sensitization and challenge. With induction of tolerance, these numbers are increased as well as demethylation of FoxP3.
http://ift.tt/2qxCbov
CDC42-related genes are upregulated in helper T cells from obese asthmatic children
Pediatric obesity-related asthma is more severe and less responsive to medications than asthma in normal-weight children. Obese asthmatic children have nonatopic TH1-polarized systemic inflammation that correlates with pulmonary function deficits, but the pathways underlying TH1-polarized inflammation are not well understood.
http://ift.tt/2pbCfFP
Cross-reactivity in Fish Allergy: A Double-Blind Placebo-Controlled Food Challenge Trial
One third of fish-allergic patients tolerate at least one fish species. Specific IgE testing can identify most patients with fish allergy and reduce the need of oral challenges in the diagnostic work-up.
http://ift.tt/2qxe5dr
The number and affinity of productive IgE pairs determine allergen activation of mast cells
IgE composition (number and concentration of IgE pairs, IgE clonality, and IgE affinity) determines number of mast cells reacting and allergen threshold for activation and may dictate the threshold allergen dose and severity of allergy symptoms in the individual allergic patient.
http://ift.tt/2pbMDx7
Desiccating stress worsens alkali burn injury by magnifying caspase-8-induced imbalance of NLRP3 and NLRP6
We reveal novel discoveries of an innate immune pathway mediated by the imbalanced activation of NLRP3 and NLRP6 promoted by caspase-8 activation in AB and secondary dry eye and create new intervention strategies to treat inflammatory diseases.
http://ift.tt/2pbFFZc
In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives
Publication date: Available online 4 May 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Amanda Silva dos Santos Aliança, Arsênio Rodrigues Oliveira, Ana Paula Sampaio Feitosa, Karla Raíza Cardoso Ribeiro, Maria Carolina Accioly Brelaz de Castro, Ana Cristina Lima Leite, Luiz Carlos Alves, Fábio André Brayner
It is estimated that the worldwide prevalence of leishmaniasis is around 12 million individuals in 80 countries, with 400,000new cases per year. In the search for new leishmanicidal agents, the hybrid phthalimido-thiazoles have been identified as an important scaffold for drug design and discovery. The present study thus reports the in vitro activity of a series of phthalimido-thiazole derivatives. Cytotoxicity against a strain of L. infantum, Vero cells, J774 macrophages and peritoneal macrophages was evaluated, as well as nitric oxide (NO) production. Activity against amastigote and promastigote forms of L. infantum and microscopic changes in the parasite and intracellular targets of the parasite were achieved. The results show that the compounds arising from hybridization of phthalimide and 1,3-thiazole exhibit promising leishmanicidal activity. Compounds 2j and 2m were the most potent of the series tested and the parasites treated with these compounds exhibited ultrastructural changes, such as cell body shrinkage, loss of cellular membrane integrity, vacuolization of cytoplasm, membrane profiles surrounding organelles and swelling of mitochondria. The data showed that these compounds reduced the survival of intracellular amastigotes and presented low toxicity for mammalian cells. The compounds produced increased NO production compared to untreated cells in non-infected macrophages. Treated promastigote forms showed an increase in the number of cells stained with propidium iodide. The compounds brought about significant changes in mitochondrial membrane potential. According to the present study, phthalimido-thiazole compounds exhibit leishmanicidal activity and could be used to develop novel antileishmaniasis drugs and explore potential molecular targets.
Graphical abstract
http://ift.tt/2pbs6J6
Large porous particles for respiratory drug delivery. Glycine-based formulations
Publication date: Available online 4 May 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): A.G. Ogienko, E.G. Bogdanova, N.A. Trofimov, S.A. Myz, A.A. Ogienko, B.A. Kolesov, A.S. Yunoshev, N.V. Zubikov, E.V. Boldyreva, A.Yu Manakov, V.V. Boldyrev
Large porous particles are becoming increasingly popular as carriers for pulmonary drug delivery with both local and systemic applications. These particles have high geometric diameters (5–30μm) but low bulk density (~0.1g/cm3 or less) such that the aerodynamic diameter remains low (1–5μm). In this study salbutamol and budesonide serve as model inhalable drugs with poor water solubility. A novel method is proposed for the production of dry powder inhaler formulations with enhanced aerosol performance (e.g. for salbutamol-glycine formulation the fine particle fraction (FPF≤4.7μm) value is 67.0±1.3%) from substances that are poorly soluble in water. To overcome the problems related to extremely poor aqueous solubility of the APIs, not individual solvents are used for spray freeze-drying of API solutions, but organic-water mixtures, which can form clathrate hydrates at low temperatures and release APIs or their complexes as fine powders, which form large porous particles after the clathrates are removed by sublimation. Zwitterionic glycine has been used as an additive to API directly in solutions prior to spray freeze-drying, in order to prevent aggregation of powders, to enhance their dispersibility and improve air-flow properties. The clathrate-forming spray freeze-drying process in the multi-component system was optimized using low-temperature powder X-ray diffraction and thermal analysis.
Graphical abstract
http://ift.tt/2pbz29f
Recovery of Online Sentence Processing in Aphasia: Eye Movement Changes Resulting From Treatment of Underlying Forms
Purpose
The present study tested whether (and how) language treatment changed online sentence processing in individuals with aphasia. Method
Participants with aphasia (n = 10) received a 12-week program of Treatment of Underlying Forms (Thompson & Shapiro, 2005) focused on production and comprehension of passive sentences. Before and after treatment, participants performed a sentence-picture matching task with active and passive sentences as eye movements were tracked. Twelve age-matched controls also performed the task once each. Results
In the age-matched group, eye movements indicated agent-first predictive processing after hearing the subject noun, followed by rapid thematic reanalysis after hearing the verb form. Pretreatment eye movements in the participants with aphasia showed no predictive agent-first processing, and more accurate thematic analysis in active compared to passive sentences. After treatment, which resulted in improved offline passive sentence production and comprehension, participants were more likely to respond correctly when they made agent-first eye movements early in the sentence, showed equally reliable thematic analysis in active and passive sentences, and were less likely to use a spatially based alternative response strategy. Conclusions
These findings suggest that treatment focused on improving sentence production and comprehension supports the emergence of more normal-like sentence comprehension processes.http://ift.tt/2qFUo0t
Permissive flexibility in successful lifelong weight management: A qualitative study among Finnish men and women
Source:Appetite, Volume 116
Author(s): Anu Joki, Johanna Mäkelä, Mikael Fogelholm
Maintaining normal weight in the current obesogenic environment is a challenge. However, some people can do it. More insight is needed to understand how and why some people succeed in long-term weight maintenance. This study uses a rare, qualitative approach by describing the thoughts of successful weight management and self-perceived requirements for success in weight maintenance. We interviewed 39 individuals who have maintained normal weight for their entire lives (men and women). The content analysis revealed a main theme: flexible, permissive and conscious self-regulation, which was divided into two subthemes (eating-related behavior and weight-related behavior). The informants reported certain routines that supported their weight management: regular eating, sufficient meal sizes, eating in response to hunger, healthy and vegetable-rich diet along with moderate feasting and flexible eating restriction. Flexibility in routines allowed freedom in their eating behavior. In addition, informants regarded themselves as physically active, and they enjoyed regular exercise. Regular weighing was generally considered unnecessary. Normal weight was regarded as a valuable and worthwhile issue, and most of the informants worked to keep their weight stable. Although the perceived workload varied among informants, the weight management strategies were similar. It was crucial to be conscious of the balance between eating and energy consumption. Further, flexibility characterized their behavior and was the basis of successful weight management. Women were more aware of weight control practices and knowledge than men, but otherwise, women and men reported similar weight management methods and attitudes. In conclusion, the interviewees who have maintained the normal weight had created a personal weight-management support environment where weight management was a lifestyle.
http://ift.tt/2q52QsZ
Identification of students with asthma in Chicago schools
Asthma is the most common chronic childhood condition, affecting 1 of every 11 children in the United States. Disparities are well documented, with minority and underserved youth disproportionately affected.1 In addition to causing medical complications that lead to emergency department visits and hospitalizations, asthma negatively affects school attendance, readiness, and achievement.2
http://ift.tt/2q4GIyW
Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder driven by complex biologic and environmental influences. AD has been divided into early-onset and late-onset forms, with some speculating that early-onset AD is driven predominantly by genetic factors, whereas late-onset disease is driven by environmental exposures.1 Among many genetic factors relevant to AD are filaggrin (FLG), an epidermal barrier protein, and thymic stromal lymphopoietin (TSLP), an interleukin 7–like cytokine that promotes TH2 cell differentiation.
http://ift.tt/2q500o4
The presence of atopy and its effect on bacterial colonization of the upper airways in children with adenoid vegetation
Publication date: Available online 3 May 2017
Source:Alergologia Polska - Polish Journal of Allergology
Author(s): Gabriela Bugova, Barbora Uhliarova, Milos Jesenak, Andrej Hajtman
Background: The aim of this study was to determine the frequency of atopy and the influence of atopy on bacterial colonization of upper airway in children with adenoid hypertrophy. Material and methods: Forty children were enrolled in the prospective study. Presence of atopy was diagnosed by skin-prick test. Differences in bacterial colonization of middle nasal meatus and nasopharynx according to the presence of atopy were analyzed. Results: Atopy was diagnosed in 75% children with adenoid hypertrophy. Presence of atopy was associated with significantly more often colonization of pathogenic bacteria (Streptococcus pneumoniae, Hemophillus influaenzae, Moraxella catarrhalis, Staphylococcus aureus) in the middle nasal meatus but not in nasopharynx (P=0.045, P=0.483, respectively). Identification of pathogenic bacteria in middle nasal meatus did not correlate with isolation of pathogenic bacteria in nasopharynx in both groups of children. Conclusion: There is a high incidence of atopy in children with adenoid hypertrophy. Atopy is related to increased colonization by pathogenic bacteria in middle nasal meatus but not in nasopharynx.
http://ift.tt/2pFhoOK
Predictors of emergency department use in children with persistent asthma in metropolitan Atlanta, Georgia
Racial disparities are evident among children with asthma in the United States, with non-Hispanic black children at particularly high risk for poor asthma outcomes, including frequent emergency department (ED) use for asthma exacerbations.
http://ift.tt/2qFV2Lt
Effect of screw-access hole and mechanical cycling on fracture load of 3-unit implant-supported fixed dental prostheses
Source:The Journal of Prosthetic Dentistry
Author(s): Fernando Mallmann, Luciano Rosa, Márcia Borba, Alvaro Della Bona
Statement of problemThe effect of screw-access holes and mechanical cycling on fracture resistance of 3-unit screw-retained zirconia-based implant-supported fixed dental prostheses (ISFDPs) is unknown.PurposeThe purpose of this in vitro study was to evaluate the effect of screw-access holes on the maximum fracture load (Lf) of 3-unit ISFDPs fabricated with the same abutment design for screw (s)-retained and cement (c)-retained with either a metal- or zirconia-based framework, testing the hypotheses that ISFDPs with screw-access holes have the lowest Lf and that mechanical cycling decreases the Lf of screw-retained ISFDPs.Material and methodsModels with fiberglass bases with 2 implants were fabricated. Special abutments were designed to allow for both s- and c-retained ISFDPs. The study considered the type of framework (s-retained metal-based and s-retained zirconia-based), fixation (s and c), and aging (a) with mechanical cycling, resulting in the following experimental groups (n=12): c-retained metal-based ISFDP; s-retained metal-based ISFDP (Ms); s-retained zirconia-based ISFDP aged by mechanical cycling (Zsa); and s-retained metal-based ISFDP aged by mechanical cycling (Msa). All ISFDPs were porcelain veneered and subjected to compressive load to failure. Fracture load data were statistically analyzed using 1-way ANOVA and Tukey range tests (α=.05). Fractography was used to evaluate the fracture surfaces.ResultsCement-retained ISFDP (Zc and Mc) showed the greatest Lf values (P<.001). Zs prostheses showed higher Lf values than those for Ms. Aging significantly decreased the Lf of Zsa but had no effect on Msa. Chipping was the failure mode most frequently found. Only Zs and Zsa ISFDPs showed catastrophic failures.ConclusionsISFDPs with screw-access holes showed lower Lf values, regardless of the framework type. Mechanical cycling affected the Lf of screw-retained zirconia-based ISFDPs.
http://ift.tt/2pEXVxI
Cover 1
Publication date: May 2017
Source:The Journal of Prosthetic Dentistry, Volume 117, Issue 5, Supplement
http://ift.tt/2peBpsQ
Identification of students with asthma in Chicago schools
Asthma is the most common chronic childhood condition, affecting 1 of every 11 children in the United States. Disparities are well documented, with minority and underserved youth disproportionately affected.1 In addition to causing medical complications that lead to emergency department visits and hospitalizations, asthma negatively affects school attendance, readiness, and achievement.2
http://ift.tt/2q4GIyW
Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder driven by complex biologic and environmental influences. AD has been divided into early-onset and late-onset forms, with some speculating that early-onset AD is driven predominantly by genetic factors, whereas late-onset disease is driven by environmental exposures.1 Among many genetic factors relevant to AD are filaggrin (FLG), an epidermal barrier protein, and thymic stromal lymphopoietin (TSLP), an interleukin 7–like cytokine that promotes TH2 cell differentiation.
http://ift.tt/2q500o4
Predictors of emergency department use in children with persistent asthma in metropolitan Atlanta, Georgia
Racial disparities are evident among children with asthma in the United States, with non-Hispanic black children at particularly high risk for poor asthma outcomes, including frequent emergency department (ED) use for asthma exacerbations.
http://ift.tt/2qFV2Lt
Vestibular syncope: A disorder associated with drop attack in Ménière’s disease
Source:Auris Nasus Larynx
Author(s): Ilmari Pyykkö, Vinaya Manchaiah, Jing Zou, Hilla Levo, Erna Kentala
ObjectiveExperiments in humans and animals indicate that vestibular influx through vestibular sympathetic reflex is an important and vital part of the regulatory system of circulation. The otolith organ adjusts the circulatory responses through the vestibular sympathetic reflex during an upright stance and may trigger a vasovagal attack of syncope. The aim of the present study was to evaluate the prevalence and association of syncope attacks among patients with Ménière's disease (MD). Vestibular syncope was defined as a sudden and transient loss of consciousness, which subsides spontaneously in people with vestibular disorders and without localizing neurological deficit.MethodsDuring clinical interactions, we encountered 5 patients with syncope during a Tumarkin attack of MD. Thereafter we evaluated data from 952 patients collected with a questionnaire from the Finnish Ménière Association (FMA). The data contained case histories with special attention to Tumarkin attacks, participation restriction, migraines, and syncope attacks. The mean age of the subjects participating in the study was 60.6 years (range 25–75 years). The duration of the disease was on average 9.8 years (range 0.5–35 years).ResultsIn the current study sample, attacks of syncope were reported by 38 patients (4%) in association with the vertigo attack. Syncope was associated with Tumarkin attacks (X2=16.7, p<0.001), migraine (X2=7.4, p<0.011), history of ischemic heart disease (X2=6.0, p<0.025), and history of cerebrovascular disease (X2=11.7, p<0.004). Duration of MD was correlated with syncope. Syncope was provoked by physical strain and environmental pressure, and was associated with impairment of the visual field (i.e., visual blurring). In logistic regression analysis, syncope was significantly associated with Tumarkin attacks (odds ratio 3.2), migraines (odds ratio 2.3) and nausea (odds ratio 1.3). The attack of syncope was experienced as frightening, and general health related quality of life (HRQoL) was significantly worsened. Also, the patients suffered more from fatigue.ConclusionThe current study indicates that patients with MD who suffer from Tumarkin attacks can suffer from syncope. It confirms the role of the otolith organ in controlling the circulatory homeostasis of the body. The actions are mediated through the vestibular sympathetic reflex.
http://ift.tt/2pFgYYw
Mucosal and systemic immune response to sublingual or intranasal immunization with phosphorylcholine
Source:Auris Nasus Larynx
Author(s): Yoshiko Maseda, Junichiro Ohori, Norimitsu Tanaka, Hiromi Nagano, Keiichi Miyashita, Yuichi Kurono
ObjectivePhosphorylcholine (PC) is a structural component of a wide variety of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. Here, the immune response in mice to PC immunization via the sublingual (SL) route versus the intranasal (IN) route was investigated in terms of efficacy and safety.MethodsBALB/c mice were immunized with PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT) or CT alone via the IN or SL route. The immune response generated was studied in terms of PC-specific antibody titers, interferon (IFN)-γ and interleukin (IL)-4 production by CD4+ T cells, and cross-reactivity of PC-specific immunoglobulin (Ig)-A antibodies in nasal washes against S. pneumoniae and non-typeable H. influenzae.ResultsSL and IN immunization with PC-KLH plus CT resulted in a marked increase in the levels of PC-specific, mucosal IgA and serum IgM, IgG, and IgA antibodies. Additionally, SL immunization elicited significantly higher levels of PC-specific IgG2a subclass antibodies and IFN-γ in serum. On the other hand, IN immunization with CT alone remarkably increased the total IgE level in serum compared with SL and IN immunization with PC-KLH plus CT. PC-specific IgA antibodies in nasal wash samples reacted to most strains of S. pneumoniae and non-typeable H. influenzae.ConclusionSL immunization is as effective as IN immunization to induce PC-specific immune responses and more effective than IN immunization to reduce the production of IgE and to prevent the sensitization to allergen causing type I allergy.
http://ift.tt/2peHHbK
PLMD: an updated data resource of protein lysine modifications
Publication date: Available online 3 May 2017
Source:Journal of Genetics and Genomics
Author(s): Haodong Xu, Jiaqi Zhou, Shaofeng Lin, Wankun Deng, Ying Zhang, Yu Xue
Post-translational modifications (PTMs) occurring at protein lysine residues, or protein lysine modifications (PLMs), play critical roles in regulating biological processes. Due to the explosive expansion of the amount of PLM substrates and the discovery of novel PLM types, here we greatly updated our previous studies, and presented a much more integrative resource of protein lysine modification database (PLMD). In PLMD, we totally collected and integrated 284,780 modification events in 53,501 proteins across 176 eukaryotes and prokaryotes for up to 20 types of PLMs, including ubiquitination, acetylation, sumoylation, methylation, succinylation, malonylation, glutarylation, glycation, formylation, hydroxylation, butyrylation, propionylation, crotonylation, pupylation, neddylation, 2-hydroxyisobutyrylation, phosphoglycerylation, carboxylation, lipoylation and biotinylation. Using the data set, a motif-based analysis was performed for each PLM type, and the results demonstrated that different PLM types preferentially recognize distinct sequence motifs for the modifications. Moreover, various PLMs synergistically orchestrate specific cellular biological processes by mutual crosstalks with each other, and we totally found 65,297 PLM events involved in 90 types of PLM co-occurrences on the same lysine residues. Finally, various options were provided for accessing the data, while original references and other annotations were also present for each PLM substrate. Taken together, we anticipated the PLMD database can serve as a useful resource for further researches of PLMs. PLMD 3.0 was implemented in PHP + MySQL and freely available at http://ift.tt/2qFAWkm.
http://ift.tt/2pFejOz
CMGene: A literature-based database and knowledge resource for cancer metastasis genes
Source:Journal of Genetics and Genomics
Author(s): Yining Liu, Zhe Li, Jiachun Lu, Min Zhao, Hong Qu
http://ift.tt/2pFlpCM
SysFinder: A customized platform for search, comparison and assisted design of appropriate animal models based on systematic similarity
Source:Journal of Genetics and Genomics
Author(s): Shuang Yang, Guoqing Zhang, Wan Liu, Zhen Wang, Jifeng Zhang, Dongshan Yang, Y. Eugene Chen, Hong Sun, Yixue Li
Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients. However, many disease mechanisms and drug effects generated from animal models are not transferable to human. To address these issues, we developed SysFinder (http://ift.tt/2pFivOp), a platform for scientists to find appropriate animal models for translational research. SysFinder offers a "topic-centered" approach for systematic comparisons of human genes, whose functions are involved in a specific scientific topic, to the corresponding homologous genes of animal models. Scientific topic can be a certain disease, drug, gene function or biological pathway. SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics. Meanwhile, SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models. Furthermore, SysFinder provides a user-friendly platform for determination of short guide RNAs (sgRNAs) and homology arms to design a new animal model. Case studies illustrate the ability of SysFinder in helping experimental scientists. SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.
http://ift.tt/2qFuZUB
DRodVir: a resource for exploring the virome diversity in rodents
Source:Journal of Genetics and Genomics
Author(s): Lihong Chen, Bo Liu, Zhiqiang Wu, Qi Jin, Jian Yang
Emerging zoonotic diseases have received tremendous interests in recent years, as they pose a significant threat to human health, animal welfare, and economic stability. A high proportion of zoonoses originates from wildlife reservoirs. Rodents are the most numerous, widespread, and diverse group of mammals on the earth and are reservoirs for many zoonotic viruses responsible for significant morbidity and mortality. A better understanding of virome diversity in rodents would be of importance for researchers and professionals in the field. Therefore, we developed the DRodVir database (http://ift.tt/2pEVHOS), a comprehensive, up-to-date, and well-curated repository of rodent-associated animal viruses. The database currently covers 7690 sequences from 5491 rodent-associated mammal viruses of 26 viral families detected from 194 rodent species in 93 countries worldwide. In addition to virus sequences, the database provides detailed information on related samples and host rodents, as well as a set of online analytical tools for text query, BLAST search and phylogenetic reconstruction. The DRodVir database will help virologists better understand the virome diversity of rodents. Moreover, it will be a valuable tool for epidemiologists and zoologists for easy monitoring and tracking of the current and future zoonotic diseases. As a data application example, we further compared the current status of rodent-associated viruses with bat-associated viruses to highlight the necessity for including additional host species and geographic regions in future investigations, which will help us achieve a better understanding of the virome diversities in the two major reservoirs of emerging zoonotic infectious diseases.
http://ift.tt/2qFYAgS
Rice Expression Database (RED): an integrated RNA-Seq-derived gene expression database for rice
Source:Journal of Genetics and Genomics
Author(s): Lin Xia, Dong Zou, Jian Sang, Xingjian Xu, Hongyan Yin, Mengwei Li, Shuangyang Wu, Songnian Hu, Lili Hao, Zhang Zhang
Rice is one of the most important stable food as well as a monocotyledonous model organism for the plant research community. Here we present RED (Rice Expression Database; http://ift.tt/2pEVDi6), an integrated database of rice gene expression profiles derived entirely from RNA-Seq data. RED features a comprehensive collection of 284 high-quality RNA-Seq experiments, integrates a large number of gene expression profiles and covers a wide range of rice growth stages as well as various treatments. Based on massive expression profiles, RED provides a list of housekeeping and tissue-specific genes and dynamically constructs co-expression networks for gene(s) of interest. Besides, it provides user-friendly web interfaces for querying, browsing and visualizing expression profiles of concerned genes. Together, as a core resource in BIG Data Center, RED bears great utility for characterizing the function of rice genes and better understanding important biological processes and mechanisms underlying complex agronomic traits in rice.
http://ift.tt/2qFzQ8t
The pivotal role of HIF-1α in lung inflammatory injury induced by septic mesenteric lymph
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Hua-Dong Sun, Yong-Jun Liu, Juan Chen, Min-Ying Chen, Bin Ouyang, Xiang-Dong Guan
Hypoxia inducible factor-1α (HIF-1α) plays an essential role in hypoxia and inflammatory response. Oxygen metabolic dysfunction and cascade amplification of inflammatory response are prominent pathophysiological characteristics in sepsis induced acute lung injury (ALI).In this study, we started with septic mesenteric lymph injection model to investigate whether HIF-1α played a role in the pathogenesis of ALI induced by septic lymph. The data demonstrated that rats injected with septic lymph showed a significant higher Lung Injury Scale and MPO(myeloperoxidase) levels than that of rats injected with normal saline/lymph. ALI was associated with a higher degree of HIF-1α expression in the lungs infused by septic lymph. Intratracheal delivery of YC-1(3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole) significantly attenuated lung inflammatory damages.Furthermore, in vitro studies, human alveolar type II epithelial cell (A549)/human pulmonary microvascular endothelial cell (HPMEC) incubated by septic lymph showed dramatically decreased cell viability, higher levels of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and excitation of HIF-1α expression (Immunofluorescence localization/RT-PCR test) simultaneously. Nevertheless, compared with the non-silencing cell lines, A549/HPMEC with HIF-1α gene silencing manifested increased viability and restrained cytokines' expression after incubation with septic lymph.These results indicate that HIF-1α expression can be induced and activated in rats during the acute lung inflammatory damages triggered by septic lymph injection and that lung inflammatory injuries occur via a HIF-1α-dependent pathway.
http://ift.tt/2p2Nvcj
Bee venom for the treatment of Parkinson’s disease: How far is it possible?
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Kamal Awad, Abdelrahman Ibrahim Abushouk, Ahmed Helal AbdelKarim, Maged Mohammed, Ahmed Negida, Ali S. Shalash
Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta leading to depletion of striatal dopamine and motor symptoms as bradykinesia, resting tremors, rigidity, and postural instability. Current therapeutic strategies for PD are mainly symptomatic and may cause motor complications, such as motor fluctuations and dyskinesia. Therefore, alternative medicine may offer an effective adjuvant treatment for PD. Bee venom therapy (BVT) has long been used as a traditional therapy for several conditions, such as rheumatoid arthritis, asthma, and skin diseases. Experimental and clinical studies showed that BVT could be an effective adjuvant treatment for PD. Several mechanisms were suggested for these findings including the ability of BVT to attenuate neuroinflammation, inhibit apoptosis of dopaminergic neurons, protect against glutamate-induced neurotoxicity, and restore normal dopamine levels in the nigrostriatal pathway. In this article, we reviewed and summarized the literature regarding the potential of BVT for the treatment of PD.
http://ift.tt/2qKqQy5
In vitro antioxidant and anticataractogenic potential of silver nanoparticles biosynthesized using an ethanolic extract of Tabernaemontana divaricata leaves
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Muniyandi Anbukkarasi, Philip A. Thomas, Joen-Rong Sheu, Pitchairaj Geraldine
Silver nanoparticles (AgNPs) have been found useful in biological systems and in medicine since they possess a large surface area to volume ratio, which confers on them several unique properties. In the present study, AgNPs that had been biosynthesized using an ethanolic extract of Tabernaemontana divaricata leaf were evaluated for putative antioxidant potential and efficacy in preventing experimental in-vitro selenite-induced opacification of the ocular lens (cataractogenesis). The antioxidant potential of the AgNPs was evaluated in-vitro by looking for radical-scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) free radicals as well as by determining reducing power. The anticataractogenic potential of the AgNPs was evaluated in an in-vitro model of selenite-induced cataractogenesis in five groups of Wistar rat lenses cultured in Dulbecco's modified Eagle's medium (DMEM) for 24h: Group I lenses (negative control) were cultured in DMEM alone; Group II lenses were exposed to sodium selenite alone (100μM); Group III lenses were exposed simultaneously to sodium selenite and the T. divaricata extract (250μg/ml); Group IV lenses were exposed simultaneously to sodium selenite and the biosynthesized AgNPs (125μg/ml); and Group V lenses were exposed to the AgNPs alone. In these lenses, gross morphological changes, as well as activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and levels of reduced glutathione (GSH) and malondialdehyde (MDA), were determined. In-vitro, the AgNPs (which were spherical in shape with an average diameter ranging from 15 to 50nm) showed potent and concentration-dependent radical-scavenging activity on DPPH and H2O2 free radicals as well as reducing power. The gross morphological changes seen in the cultured rat lenses were: all eight control (Group I) lenses remained transparent; dense opacification was noted in all eight selenite-challenged untreated (Group II) lenses; in selenite-challenged, simultaneously T. divaricata extract-treated (Group III) lenses, no opacification occurred in seven of eight (87.5%) lenses and only minimal opacification in one (12.5%) lens; all the eight Group IV (selenite-challenged, simultaneously AgNPs-treated) lenses did not show any opacification; and all the eight Group V lenses (exposed to AgNPs alone) remained as transparent as control lenses. The mean activities of CAT, SOD, GPx and GST, and the mean levels of GSH, were significantly (p<0.05) lower in Group II lenses than those in Groups I, III, IV and V lenses, while the mean MDA level was significantly (p<0.05) higher in Group II lenses than those in Groups I, III, IV and V lenses; oxidative damage possibly occurred in Group II lenses, whereas this appears to have been prevented in Groups III and IV lenses. These observations suggest that the T. divaricata leaf ethanolic extract, and also the AgNPs biosynthesized using the T. divaricata extract, possess effective in-vitro antioxidant activity and the potential to prevent experimental selenite-induced opacification in cultured Wistar rat lenses.
Graphical abstract
http://ift.tt/2p2wIGB
β-Glucosidase inhibition sensitizes breast cancer to chemotherapy
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Xiao Zhou, Zhen Huang, Huawei Yang, Yi Jiang, Wei Wei, Qiuyun Li, Qinguo Mo, Jianlun Liu
The resistance to therapy is a major clinical challenge for advanced stage breast cancer. Identification of novel potential therapeutic targets is needed to overcome chemoresistance. In this work, we identified a target that was critically involved in breast cancer growth and chemoresistance. We demonstrated that β-glucosidase expression and activity were significantly upregulated in breast cancer tissues and a panel of cell lines compared to normal adjacent breast tissues and cell lines. β-glucosidase overexpression activated PI3K/Akt/mTOR signalling, leading to increased cell growth. In contrast, β-glucosidase inhibition by siRNA depletion and pharmacological approach using conduritol B epoxide (selective β-glucosidase inhibitor) suppressed growth and induced apoptosis in breast cancer cells. Importantly, β-glucosidase inhibition significantly sensitized breast cancer cells to chemotherapy in vitro and in vivo, suggesting that inhibiting β-glucosidase effectively targeted breast cancer cells that were resistant to elimination by chemotherapeutic agent alone. We demonstrated the positive role of β-glucosidase in breast cancer growth and survival. Our work also suggested that inhibiting β-glucosidase as a possible alternative therapeutic strategy to overcome chemoresistance in breast cancer.
http://ift.tt/2p2NuoL
Alcohol aggravates stress-induced cognitive deficits and hippocampal neurotoxicity: Protective effect of melatonin
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Prabha Rajput, Ashok Jangra, Mohit Kwatra, Abhishek Mishra, Mangala Lahkar
Stressful events and alcohol abuse are the cumbersome situations which can synergistically predispose the negative effects on the brain. Oxidative stress generated by chronic immobilization and alcohol consumption cause severe neurotoxicity in the hippocampus region that ultimately leads to cognitive dysfunction. In the current study, we have investigated the involvement of NF-κB/Nrf/HO-1 transduction pathway in stress and alcohol exposed animals. Male Swiss albino mice were given alcohol (ALC) (15% v/v) or restraint stress (RS) or both (RS for 6h per day) up to 28days. We found increased ALC consumption in the ALC+RS group as compared to the ALC group. Morris water maze (MWM) test and novel object recognition test (NORT) revealed the spatial and recognition memory impairment in RS and ALC+RS group. ALC+RS group showed more profound oxidative stress and augmentation of pro-inflammatory cytokine (IL-1β) as compared to RS or ALC group alone. Melatonin (20mg/kg, p.o) treatment for 14days significantly prevented the raised oxidative stress, release of IL-1β, GSH depletion and augmentation of AChE activity in the hippocampus. Moreover, semi-quantitative reverse transcriptase PCR results showed that combined exposure of ALC and RS leads to over-activation of NF-κB transduction inflammatory pathway and down-regulation of the Nrf2/HO-1 axis which was significantly ameliorated by the melatonin treatment. In conclusion, our results indicated that ALC+RS exerted the deleterious effects on the hippocampus which were alleviated by the melatonin treatment.
http://ift.tt/2qK0WKM
Novel purification of 1’S-1’-Acetoxychavicol acetate from Alpinia galanga and its cytotoxic plus antiproliferative activity in colorectal adenocarcinoma cell line SW480
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): R.G. Baradwaj, M.V. Rao, T. Senthil Kumar
Alpinia galanga (L.) Willd. is a valuable medicinal crop found in specific tropical regions of southeast Asia. Its crude extracts are well known for their wide medicinal properties and many compounds identified from these extracts are of great interest currently. 1'S-1'-Acetoxychavicol acetate (ACA) obtained from rhizomes of A.galanga is one such well-illustrated compound. This study strives to progress and simplifies the purification protocol for ACA from A.galanga rhizomes. It also studies the cytotoxicity and antiproliferative activity of ACA against Dukes' type B, colorectal adenocarcinoma (SW480). HPLC standardisation was carried out for purification of ACA from rhizomes of Alpinia galanga. MTT assay was executed to estimate the IC50 value of ACA against SW480 cell line. This value was used to study the apoptosis, nuclear morphological changes and mitochondrial membrane permeability using Acridine orange/ethidium bromide, DAPI, and JC-1 staining. The DNA fragmentation assay was used to substantiate the nuclear fragmentation of DNA observed in the DAPI staining. Further, cell cycle analysis was performed using flow cytometry to study the exact stage of the cell cycle where SW480 cells are arrested due to ACA, western blot analysis of relevant genes were done to further understand at molecular level. A comprehensive 1.89g of 1'S-1'-Acetoxychavicol acetate (ACA) was recovered from 500g of A.galanga rhizomes. ACA significantly suppressed the proliferation of SW480 cells at an IC50 of 80μM (48h). The mode of SW480 cell death due to ACA was initially identified as apoptosis and cell cycle halted at G0/G1 checkpoint with considerable DNA damage and mitochondrial depolarization. The expression of p21 was increased and concomitantly Cyclin D was downregulated in ACA treated in comparison to control. This study suggests that 1'S-1'-Acetoxychavicol acetate has potent anti-colorectal adenocarcinoma activity.
http://ift.tt/2p2NsNF
Nobiletin improves propofol-induced neuroprotection via regulating Akt/mTOR and TLR 4/NF-κB signaling in ischemic brain injury in rats
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Yuzhen Zheng, Jinmei Bu, Liang Yu, Jun Chen, Haigen Liu
BackgroundStroke is regarded as one of the main health concerns globally, presenting with high mortality and morbidity rates. Cerebral ischemic damage and infarction are critically associated with stroke. Various mechanisms related to inflammation, oxidative stress and excitotoxicity are found to be involved in ischemic damage. Very short time period for treatment has necessitated in development of more effective neuroprotective agents. Study aimed in investigated the effects of nobiletin on experimentally induced ischemic brain injury and also to assess whether nobiletin potentiated the neuroprotective effects of propofol.MethodsMale Sprague–Dawley rats were subjected to ischemia/reperfusion (I/R) injury. Induction of cerebral infarction and I/R was done by middle cerebral artery occlusion (MCAO). Nobiletin (100 or 200mg/kg b.wt.) was intragastrically administered to rats for 9 days before ischemia induction and on the day of induction nobiletin was administered an hour prior. Separate group of rats were post-conditioned with propofol (50mg/kg/h; i.v.) for 30min following 24h of reperfusion.ResultsPropofol post-conditioning either with or without administration of nobiletin prior I/R injury attenuated pulmonary edema, neuronal apoptosis and reduced cerebral infarct volume. Overproduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and nitric oxide following I/R were reduced. Propofol either alone or with prior nobiletin treatment had down-regulated TLR4 and TLR4-mediated NF-κB signaling and caused activation of Akt/mTOR cascade.ConclusionPropofol post-conditioning either with nobiletin prior I/R injury was found to be more effective than propofol alone, suggesting the positive effects of nobiletin on propofol-mediated anti-inflammatory and neuroprotective effects.
http://ift.tt/2qKfZE2
Editorial Board
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
http://ift.tt/2p2P8Xs
Antigen processing and presentation in the thymus: implications for T cell repertoire selection
Kenta Kondo | Kensuke Takada | Yousuke Takahama
http://ift.tt/2qJZXdi
Context for Practice: Impact of WOC Nurse in the Acute Care Setting.
Author: Gray, Mikel
Page: 208-209
http://ift.tt/2qFDbnR
Pressure Injury in a Community Population: A Descriptive Study.
Author: Corbett, Lisa Q.; Funk, Marjorie; Fortunato, Gilbert; O'Sullivan, David M.
Page: 221-227
http://ift.tt/2pEZDPl
WOCN 2016 Guideline for Prevention and Management of Pressure Injuries (Ulcers): An Executive Summary.
Author: Wound, Ostomy and Continence Nurses Society-Wound Guidelines Task Force
Page: 241-246
http://ift.tt/2qFBR4b
Management of Central Venous Access Device-Associated Skin Impairment: An Evidence-Based Algorithm.
Author: Broadhurst, Daphne; Moureau, Nancy; Ullman, Amanda J.; The World Congress of Vascular Access (WoCoVA) Skin Impairment Management Advisory Panel
Page: 211-220
http://ift.tt/2pEZrzy
Management of Central Venous Access Device-Associated Skin Impairment: An Evidence-Based Algorithm.
Author:
Page: E1
http://ift.tt/2qFUC7O
Pressure Mapping of a Standard Hospital Recliner and Select Cushions With Healthy Adults: A Comparative Study.
Author: Slayton, Stephanie; Morris, Paula; Brinkley, Jason
Page: 228-235
http://ift.tt/2qFDcIr
Effect of a Patient-Repositioning Device in an Intensive Care Unit On Hospital-Acquired Pressure Injury Occurences and Cost: A Before-After Study.
Author: Edger, Melinda
Page: 236-240
http://ift.tt/2pEYabM
Quality of Life in Chinese Persons Living With an Ostomy: A Multisite Cross-sectional Study.
Author: Geng, Zhaohui; Howell, Doris; Xu, Honglian; Yuan, Changrong
Page: 249-256
http://ift.tt/2pFe4mx
North America Wound, Ostomy, and Continence and Enterostomal Therapy Nurses Current Ostomy Care Practice Related to Peristomal Skin Issues.
Author: Colwell, Janice C.; McNichol, Laurie; Boarini, Joy
Page: 257-261
http://ift.tt/2qFCpqU
Implementation of an Evidence-Based and Content Validated Standardized Ostomy Algorithm Tool in Home Care: A Quality Improvement Project.
Author: Bare, Kimberly; Drain, Jerri; Timko-Progar, Monica; Stallings, Bobbie; Smith, Kimberly; Ward, Naomi; Wright, Sandra
Page: 262-266
http://ift.tt/2pEZpYs
Identification of Key Odorants in Used Disposable Absorbent Incontinence Products.
Author: Hall, Gunnar; Alenljung, Susanne; Forsgren-Brusk, Ulla
Page: 269-276
http://ift.tt/2qFRtoG
Sensory Characterization of Odors in Used Disposable Absorbent Incontinence Products.
Author: Widen, Helene; Alenljung, Susanne; Forsgren-Brusk, Ulla; Hall, Gunnar
Page: 277-282
http://ift.tt/2qFRrNA
Relationship of Wound, Ostomy, and Continence Certified Nurses and Healthcare-Acquired Conditions in Acute Care Hospitals.
Author: Boyle, Diane K.; Bergquist-Beringer, Sandra; Cramer, Emily
Page: 283-292
http://ift.tt/2pEVFGH
Fistula Isolation and the Use of Negative Pressure to Promote Wound Healing: A Case Study.
Author: Reider, Kersten E.
Page: 293-298
http://ift.tt/2qFxPJk
Educational Kiosk for Continuing Education on Pressure Injuries.
Author: Chaplain, Valerie
Page: 299-300
http://ift.tt/2pFe2Lr
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