Literature Commentary.

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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Neuroimaging "HINTS" of the Lateral Medullary Syndrome.

A series of neuroimaging studies illustrates many of the key findings of the lateral medullary syndrome. (C) 2017 by North American Neuro-Ophthalmology Society

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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

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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

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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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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

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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.



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Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei

Publication date: Available online 4 May 2017
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.



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Estrogen receptor-related receptor γ regulates testicular steroidogenesis through direct and indirect regulation of steroidogenic gene expression

Publication date: Available online 4 May 2017
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.



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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.



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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.



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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.



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Corrigendum to “Development of SERS substrate using phage-based magnetic template for triplex assay in sepsis diagnosis” [Biosens. Bioelectron. 85 (2016) 522–528]

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Anh H. Nguyen, Yesol Shin, Sang Jun Sim




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Metal ion detection using functional nucleic acids and nanomaterials

Publication date: 15 October 2017
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.



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Editorial Board

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95





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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.



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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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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.

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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

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

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

Permissive flexibility in successful lifelong weight management: A qualitative study among Finnish men and women

Publication date: 1 September 2017
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

Effect of screw-access hole and mechanical cycling on fracture load of 3-unit implant-supported fixed dental prostheses

Publication date: Available online 3 May 2017
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

CMGene: A literature-based database and knowledge resource for cancer metastasis genes

Publication date: Available online 4 May 2017
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

Publication date: Available online 4 May 2017
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

Publication date: Available online 3 May 2017
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

Publication date: Available online 4 May 2017
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

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

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.



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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.



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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.



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Editorial Board

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90





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Context for Practice: Impact of WOC Nurse in the Acute Care Setting.

Author: Gray, Mikel

Page: 208-209

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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

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Management of Central Venous Access Device-Associated Skin Impairment: An Evidence-Based Algorithm.

Author:

Page: E1

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Pressure Injury in a Community Population: A Descriptive Study.

Author: Corbett, Lisa Q.; Funk, Marjorie; Fortunato, Gilbert; O'Sullivan, David M.

Page: 221-227

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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

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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

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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

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

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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

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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

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Identification of Key Odorants in Used Disposable Absorbent Incontinence Products.

Author: Hall, Gunnar; Alenljung, Susanne; Forsgren-Brusk, Ulla

Page: 269-276

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Sensory Characterization of Odors in Used Disposable Absorbent Incontinence Products.

Author: Widen, Helene; Alenljung, Susanne; Forsgren-Brusk, Ulla; Hall, Gunnar

Page: 277-282

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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

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Fistula Isolation and the Use of Negative Pressure to Promote Wound Healing: A Case Study.

Author: Reider, Kersten E.

Page: 293-298

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Educational Kiosk for Continuing Education on Pressure Injuries.

Author: Chaplain, Valerie

Page: 299-300

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WOCN(R)-Accredited Professional Education Programs.

Author:

Page: 302-303

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Evaluating Surgical Delay Using Infrared Thermography in an Island Pedicled Perforator Flap Rat Model

J reconstr Microsurg
DOI: 10.1055/s-0037-1602776

Background The aim of this study was to examine the usefulness of infrared (IR) thermography in visualizing the dilation of the choke vessels in a delayed pedicled perforator flap rat model. Methods A three-territory island flap was designed and harvested on one side of the rat dorsum. The flap was divided into five regions. In the normal group (n = 8), IR thermal imaging was correlated with the postmortem arteriography for the location of angiosomes, linking patterns, perforator diameter, and temperature on each region. The delay group (n = 35) was divided into seven groups according to various delay periods. At different time intervals, the delay group was compared with the normal group according to link pattern and temperature on each region. Results IR thermal imaging showed that a white hotspot existed on the surface of each angiosome; the true anastomotic vessels manifested a continuous white band linking the white hotspots on angiosomes, whereas the choke vessels presented a red zone in between adjacent hotspots. After delay, the dilation of the choke vessels manifested itself as the replacement of the red zone between adjacent hotspots by the white band on IR thermography. In addition, the delayed flap presented a phenomenon of rise and fall in temperature over time. Conclusion IR thermography can accurately visualize the process of the dilation of choke vessels after a surgical delay. The chronological change in the IR thermal imaging combined with the temperature change in the delayed flap might be useful to determine the optimal delay period.
[...]

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One versus Two Venous Anastomoses in Microvascular Upper Extremity Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0037-1602759

Background Free tissue transfers are routinely performed for reconstruction of the upper limb. Main complication in free flap surgery still stems from vascular compromise and many technical controversies exist regarding the technical details of how to perform the microvascular anastomosis. This study evaluates outcomes regarding the execution of one versus two venous anastomoses for upper limb reconstruction. Methods In this study, 79 patients underwent 86 free anterolateral thigh (ALT) or groin flaps for upper limb reconstruction after trauma, infection, or malignancies. The data were retrospectively screened for patients' demographics, perioperative details, flap survival, and surgical complications. The cases were divided into two groups regarding the number of performed venous anastomoses: one versus two veins. Results No significant differences existed between the two groups regarding preoperative comorbidities (ALT: 16 one, 21 two veins; groin: 16 one, 33 two veins). Overall, there was no significant difference regarding the rate of major (1 vein: 18.8% vs. 2 veins: 20.4%; p > 0.05) and minor (1 vein: 3.1% vs. 2 veins: 3.7%; p > 0.05) surgical complications during the 3-month follow-up period. Major complications included total flap losses of 9.4% (1 vein) versus 7.4% (2 veins) (p > 0.05). Conclusion This study analyzed a series of microsurgical reconstructions with a focus on the impact of the number of performed venous anastomoses. The findings suggest that successful free tissue transfer for upper limb reconstruction can be achieved independent of the number of venous anastomoses. However, to promote additional safety, a second vein should be performed whenever technically possible.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Donor-Site Morbidity of Free Muscle and Perforator Flaps: Comparison of the Gracilis Muscle Flap and the Anterolateral Thigh Flap

J reconstr Microsurg
DOI: 10.1055/s-0037-1602724

Background Both the gracilis muscle flap and the anterolateral thigh (ALT) flap have been described as successful reconstructive options for defect coverage after trauma or tumor resection. In general, free perforator flaps are considered to generate less donor-site morbidity than muscle flaps. Here, we put this hypothesis to the test. Methods In this study, 193 patients who had undergone free flap reconstruction with either free gracilis muscle flaps (n = 131) or ALT flaps (n = 62) were included. Subjective patient satisfaction with the aesthetic and functional outcome of the donor sites was assessed using a self-report questionnaire as well as the Lower Extremity Functional Scale (LEFS). Results Comparing the donor-site morbidity of free ALT and gracilis flaps, the LEFS revealed no significant differences in functional impairment (p = 0.6447) of the lower extremity. The donor-site scar was significantly longer after ALT flap harvest (mean: 21.16 cm) than after gracilis muscle flap harvest (mean: 14.17 cm; p < 0.0001). Furthermore, donor-site numbness was significantly greater in the ALT group than in the gracilis group (p = 0.0068). Conclusion No significant differences in functional impairment of the lower extremity were reported after gracilis muscle and ALT flap harvest. Regarding scar length and level of numbness of the donor site, the gracilis muscle flap was shown to be superior to the ALT flap.
[...]

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Development and Evaluation of a Simulation Model for Microvascular Anastomosis Training

J reconstr Microsurg
DOI: 10.1055/s-0037-1602760

Background Many plastic surgery training programs have implemented microvascular preparatory courses. However, these courses vary in length across institutions, lack formal assessment, and trainees receive certificates of completion rather than competency. In addition, many institutions use animate tissues as practice models which may not be readily available, require special treatment or storage, and lack consistency across vessel segments. In this study, we developed a proficiency-based training microvascular anastomosis curriculum using a synthetic model. In addition, we developed and validated a scoring rubric and patency testing apparatus. Methods Proficiency benchmarks were developed by evaluating four plastic surgeons performing interrupted end-to-end anastomoses on synthetic vessels mounted superficially and at depth. Using a pretest–posttest design, seven plastic surgery residents from two institutions were asked to train to proficiency on the superficial exercise. Skills transfer was evaluated using a vessel mounted at depth. Each anastomosis was scored on 11 metrics of mechanics, completion time, stenosis, and leakage. Results Experts outperformed residents prior to engaging in the training curriculum, confirming construct validity. Residents' skills significantly improved on 10 of 14 metrics after training, confirming curriculum effectiveness. Only one resident was able to achieve all proficiency benchmarks on two consecutive training trials. Skills learned on the superficially mounted vessel moderately transferred to the vessel mounted at depth as evidenced by significant pre- to posttest learning gains for 4 of the 14 metrics. Conclusion The proficiency goals may have been overly stringent; however, residents improved microvascular anastomosis skills on the majority of metrics by engaging in simulation-based training using a readily available synthetic model.
[...]

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Lycopene Improves Insulin Sensitivity through Inhibition of STAT3/Srebp-1c-Mediated Lipid Accumulation and Inflammation in Mice fed a High-Fat Diet

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-101919

In the past few years, metabolic disorders, such as type 2 diabetes and metabolic syndrome, has reached global prevalence. Lycopene is one of the major carotenoids in tomatoes, watermelons, red grapefruits, and guava. In the current study, using high fat diet (HFD)-fed mice, we investigated the effect of Lycopene on insulin resistance. We showed that diet containing Lycopene significantly prevented HFD-induced increase of fasting blood glucose and insulin level, glucose and insulin intolerance, and decrease of hepatic glycogen content. We found that Lycopene notably prevented the increase of IL-1β, TNFα and CRP levels in mice fed HFD. We showed that Lycopene improved the lipid profiles in HFD-fed mice, as evidenced by decrease of systemic and hepatic TC, TG and LDL, and increase of HDL. Lycopene suppressed the increase of the expression of Srebp-1c, FAS and ACC-1 in mice fed HFD. The administration of Lycopene notably prevented the expression and phosphorylation of STAT3 in livers of mice induced by HFD. The treatment of adenovirus carrying STAT3 significantly suppressed the decrease of Srebp-1c expression induced by Lycopene. Furthermore, enhancement of STAT3 signaling by adenovirus markedly blocked the reduction of fasting blood glucose and insulin level. In conclusion, in the current study, we found that Lycopene prevented STAT3 signaling and inhibited Srebp-1c and downstream gene expression, resulting in inhibition of lipid accumulation, inflammation, insulin resistance and metabolic dysfunction. Overall, the data in the study provide better understanding of the beneficial effects of Lycopene against insulin resistance and metabolic disorder.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Direct radiocarbon dating and DNA analysis of the Darra-i-Kur (Afghanistan) human temporal bone

Publication date: June 2017
Source:Journal of Human Evolution, Volume 107
Author(s): Katerina Douka, Viviane Slon, Chris Stringer, Richard Potts, Alexander Hübner, Matthias Meyer, Fred Spoor, Svante Pääbo, Tom Higham
The temporal bone discovered in the 1960s from the Darra-i-Kur cave in Afghanistan is often cited as one of the very few Pleistocene human fossils from Central Asia. Here we report the first direct radiocarbon date for the specimen and the genetic analyses of DNA extracted and sequenced from two areas of the bone. The new radiocarbon determination places the find to ∼4500 cal BP (∼2500 BCE) contradicting an assumed Palaeolithic age of ∼30,000 years, as originally suggested. The DNA retrieved from the specimen originates from a male individual who carried mitochondrial DNA of the modern human type. The petrous part yielded more endogenous ancient DNA molecules than the squamous part of the same bone. Molecular dating of the Darra-i-Kur mitochondrial DNA sequence corroborates the radiocarbon date and suggests that the specimen is younger than previously thought. Taken together, the results consolidate the fact that the human bone is not associated with the Pleistocene-age deposits of Darra-i-Kur; instead it is intrusive, possibly re-deposited from upper levels dating to much later periods (Neolithic). Despite its Holocene age, the Darra-i-Kur specimen is, so far, the first and only ancient human from Afghanistan whose DNA has been sequenced.



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Australopithecus sediba and the emergence of Homo: Questionable evidence from the cranium of the juvenile holotype MH 1

Publication date: June 2017
Source:Journal of Human Evolution, Volume 107
Author(s): William H. Kimbel, Yoel Rak
Malapa Hominin (MH) 1, an immature individual whose second permanent molars had recently reached occlusion at the time of death, is the holotype of Australopithecus sediba, a 2-myr-old South African taxon that has been hypothesized to link phylogenetically australopith-grade hominins to the Homo clade. Given the existence of 2.8 myr-old fossils of Homo in eastern Africa, this hypothesis implies a ghost lineage spanning at least 800 kyr. An alternative hypothesis posits a unique relationship between A. sediba and Australopithecus africanus, which predates the Malapa hominins in southern Africa and whose phylogenetic relationships remain ambiguous. The craniofacial morphology of MH 1 looms large in the framing of the two hypotheses. We evaluated these alternatives in two ways. First, we investigated whether the craniofacial morphology of MH 1 was ontogenetically stable at death. Based on data from a late-growth series of chimpanzee, gorilla, and modern human crania, we found that key aspects of MH 1's resemblance to Homo can be accounted for by its immaturity. Second, we studied MH 1 with an eye to identifying craniofacial synapomorphies shared with A. africanus. In this case, MH 1 shows unambiguous affinities in its zygomaticomaxillary and supraorbital morphology to crania from Sterkfontein Member 4, which we found to exhibit unusual derived morphology compared to Homo and other australopiths. We argue that MH 1 provides clear evidence that A. sediba was uniquely related to A. africanus and that the hypothesis of an extensive ghost lineage connecting A. sediba to the root of the Homo clade is unwarranted.



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Interpretation of footprints from Site S confirms human-like bipedal biomechanics in Laetoli hominins

Publication date: Available online 4 May 2017
Source:Journal of Human Evolution
Author(s): David A. Raichlen, Adam D. Gordon




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Local injection to sciatic nerve of DEX reduces pain behaviors, SGCs activation, NGF expression and sympathetic sprouting in CCI rats

Publication date: Available online 4 May 2017
Source:Brain Research Bulletin
Author(s): Jing-ru Wu, Hui Chen, Deng-xin Zhang, Kai Jiang, Ying-ying Yao, Ming-ming Zhang, Bo Zhou, Jie Wang
Neuropathic pain has become an intractable health threat, with its profound effect on quality of life. Dorsal root ganglia (DRG) is evidenced to play a crucial role in neuropathic pain. The peripheral nociceptive afferents seem to be essential not only to initiate the process of neuropathic pain, but also to maintain and modulate it. Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptor (α2-AR), has provided significant analgesia in neuropathic pain. In the present study, we found that local injection to sciatic nerve of DEX alleviated heat hypersensitivity induced by chronic constriction injury (CCI). Western blotting revealed that DEX inhibited the over-expression of nerve growth factor (NGF) significantly. Immunohistofluorescence results showed that DEX inhibited glia cells activation and sympathetic sprouting simultaneously in DRG. Our study suggests that DEX attenuates neuropathic pain in CCI rats by down-regulation of satellite glial cell (SGC) activation, NGF expression and sympathetic sprouting.



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The protective effect of astaxanthin on learning and memory deficits and oxidative stress in a mouse model of repeated cerebral ischemia/reperfusion

Publication date: Available online 4 May 2017
Source:Brain Research Bulletin
Author(s): Yan Xue, Zhenzhen Qu, Jian Fu, Junli Zhen, Wenjing Wang, Yunlei Cai, Weiping Wang
Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorders, such as vascular cognitive impairment (VCI). The present study was performed to investigate the potential neuroprotective effect of the antioxidant astaxanthin (ATX) in a mouse model of VCI. VCI was induced in male ICR mice by repeated occlusion of the bilateral common carotid artery, leading to repeated cerebral ischemia/reperfusion (IR) injury. After surgery, the mice received ATX or an equal volume of vehicle by daily intragastric administration for 28 days. The results showed that ATX treatment ameliorated learning and memory deficits after repeated cerebral IR. ATX administration rescued the number of surviving pyramidal neurons in the CA1 and CA3 regions. The concentration of malondialdehyde was decreased, and the levels of reduced glutathione and superoxide dismutase in the hippocampus were increased. Electron microphotography revealed that damage to the ultrastructure of neurons was also reduced by ATX administration. In addition, the expression levels of Cytochrome C (Cyt C), cleaved Caspase-3 and Bax were lower and the expression of Bcl-2 was higher compared to control IR mice. Our findings demonstrate that ATX is able to suppresse learning and memory impairment caused by repeated cerebral IR and that this effect is associated with attenuation of oxidative stress.



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Subcutaneous implant breast reconstruction: time to reconsider?

Publication date: Available online 4 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Marios – Konstantinos Tasoulis, Fahad Mujtaba Iqbal, Simon Cawthorn, Fiona MacNeill, Raghavan Vidya
Improvements in breast surgery techniques such as skin and nipple preserving mastectomy and innovative prosthetics (implants, acellular dermal matrices and meshes) is renewing interest in subcutaneous (pre-pectoral) implant reconstruction. The aim of this paper is to review the current literature in an attempt to provide a rationale that may support a return to subcutaneous implant placement, so minimising the pain and functional problems resulting from submuscular breast reconstruction.



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Is neoadjuvant chemoradiotherapy always necessary for mid/high local advanced rectal cancer: A comparative analysis after propensity score matching

Publication date: Available online 4 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Yiyi Zhang, Yanwu Sun, Zongbin Xu, Pan Chi, Xingrong Lu
AimThis study was aimed to compare perioperative and oncological outcomes of mid/high locally advanced midrectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (NCRT) vs. surgery alone, and to identify risk factors for local recurrence in mid/high LARC.MethodA total of 471 mid/high LARC patients treated with surgery alone or NCRT (50.4 Gy in 28 fractions) with concurrent FOLFOX/XELOX followed by TME in 6–8 weeks from 2008 to 2014 were matched 1:1 by using propensity score analysis. Perioperative and survival outcome was compared between groups. Multivariate analyse was performed to identify risk factors for local recurrence.ResultsTwo hundred and two patients were matched for the analysis. Postoperative morbidity was similar between groups. With a mean follow-up of 57 months, the 5-year overall survival (NCRT vs. surgery alone: 80.4% vs. 81.4%; p = 0.978), 5-year local recurrence rate (3.1% vs. 5%; p = 0.467), and 5-year distant metastasis rates between two groups (29.5% vs. 23.7%; p = 0.140) was similar between two groups. Cox regression analysis showed that the circumferential resection margin (CRM) involvement (OR = 5.205, p = 0.005) was the only risk factor for local recurrence in mid/high LARC patients.ConclusionIn matched cohorts of mid/high LARC patients, surgery alone provided comparable oncological outcome, when compared with NCRT. CRM involvement was the only risk factor for local recurrence in mid/high rectal cancer. NCRT may not be always needed in mid/high LARC. A threatened CRM could be diagnosed up front and prevented by selecting CRT for these patients.



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Survival after breast cancer local recurrence according to therapeutic strategies

Publication date: Available online 4 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): G. Houvenaeghel, J.M. Boher, V. Michel, M. Bannier, M. Minsat, A. Tallet, M. Cohen, M. Butarelli, M. Resbeut, E. Lambaudie
AimsTo compare survival outcomes after mastectomy (Mt) and lumpectomy plus interstitial brachytherapy (LpIB) in the treatment of breast cancer local recurrence (LR) occurring after conservative surgery.MethodsMedical records of patients treated for an isolated LR from January 1, 1981 to December 31, 2009 were reviewed. To overcome the bias due to the fact that treatment choice (Mt or LpIB) was based on prognostic factors with LpIB proposed preferentially to women with good prognosis, Mt and LpIB populations were matched and compared with regard to overall survival (OS) and metastasis free survival (MFS).ResultsAmong 348 patients analyzed, 66.7 % underwent Mt, 17.8 % LpIB and 15.5% Lp alone. After a median follow-up of 73.3 months, 65 patients had died (42/232 Mt, 8/62 LpIB, 15/54 Lp). Before matching, OS and MFS at 5 years were significantly better in the LpIB compared to the Mt group, due to significantly more frequent poor prognostic factors in the latter (p=0,07 and p=0,09 respectively, log-rank significance limit of 10%). After matching, the benefits of LpIB disappeared since MFS and OS rates were not significantly different in both groups (p=0.68 and 0.88 respectively). After LpIB, the second LR rate was 17% at 5 years and 30% at 10 years.ConclusionA second conservative breast cancer treatment associating lumpectomy and interstitial brachytherapy is possible for selected patients with LR, without decrease in neither OS nor MFS compared to mastectomy.



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TLR2 mediates autophagy through ERK signaling pathway in Mycoplasma gallisepticum-infected RAW264.7 cells

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Ziyin Lu, Daoyuan Xie, Ying Chen, Erjie Tian, Ishfaq Muhammad, Xueping Chen, Yusong Miao, Wanjun Hu, Ziyong Wu, Huili Ni, Jiuqing Xin, Yuan Li, Jichang Li
Toll-like receptor 2 (TLR2) plays a crucial role in early innate immune response of host to various microorganisms. Mycoplasma gallisepticum (MG) is one of the major pathogen that can cause chronic respiratory diseases in chickens, but the molecular mechanism of MG infection still remained unclear. In this study, we examined the typical hallmarks of autophagy and multiple signaling pathways by western blot, immunofluorescence microscopy and electron microscopy. The results indicated that infection of mouse macrophage cell line RAW264.7 with MG activated autophagy and mitogen-activated protein kinases (MAPKs). Silencing of TLR2 by siRNA substantially down-regulated MG-triggered autophagy in macrophages, and markedly reduced MG-induced extracellular regulated protein kinase (ERK) in macrophages but did not down-regulate c-Jun N-terminal kinase (JNK) and p38. Importantly, in macrophages, inhibition of ERK by PD98059 (ERK inhibitor) also significantly attenuated the level of autophagy upon MG infection, and the simultaneous treatment of TLR2 siRNA and PD98059 showed a similar effect on MG-induced autophagy as compared with TLR2 siRNA treatment alone. These findings thus demonstrate that TLR2 may mediate MG-induced autophagy through ERK signaling pathway in macrophage.



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