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Yanli Wang, Yanling Wang, Ran Sun, Xingrao Wu, Xu Chu, Shuhu Zhou, Xibin Hu, Lingyun Gao, Qingxia Kong
BACKGROUND: Temporal lobe epilepsy (TLE) is a common and often refractory brain disease that is closely correlated with inflammation. Alpha-methyl-L-tryptophan (AMT) is recognized as a surrogate marker for epilepsy, characterized by high uptake in the epileptic focus. There are many advantages of using the magnetic targeting drug delivery system of superparamagnetic iron oxide nanoparticles (SPIONs) to treat many diseases, including epilepsy. We hypothesized that AMT and an IL-1β monoclonal antibody (anti-IL-1β mAb) chelated to SPIONs would utilize the unique advantages of SPIONs and AMT to deliver the anti-IL-1β mAb across the blood-brain barrier (BBB) as a targeted therapy...
December 4, 2018: Journal of Translational Medicine
Nils Kunze-Szikszay, Karoline Walliser, Jakob Luther, Barbara Cambiaghi, Verena Reupke, Christian Dullin, Wolfgang Vautz, Felix Bremmer, Ursula Telgheder, Cornelia Zscheppank, Michael Quintel, Thorsten Perl
OBJECTIVES: The detection of microbial volatile organic compounds or host response markers in the exhaled gas could give an earlier diagnosis of ventilator-associated pneumonia. Gas chromatography-ion mobility spectrometry enables noninvasive, rapid, and sensitive analysis of exhaled gas. Using a rabbit model of ventilator-associated pneumonia we determined if gas chromatography-ion mobility spectrometry is able to detect 1) ventilator-associated pneumonia specific changes and 2) bacterial species-specific changes in the exhaled gas...
November 30, 2018: Critical Care Medicine
Amparo Alvarez-Valdes, Ana I Matesanz, Josefina Perles, Célia Fernandes, João D G Correia, Filipa Mendes, Adoracion G Quiroga
Novel bisphosphonate platinum complexes: [Pt(isopropylamine)2 (BP)]NO3 (BP = pamidronate and alendronate) have been synthesized and characterized. Their monomeric structure contains a bisphosphonate acting as chelate ligand through its oxygen atom donors, conferring the compound's cationic structure with a good solubility in water. The study of the compounds in solution showed high stability up to 24 h. The cytotoxicity in cancer cell lines has been assessed. We also present preliminary studies on the evaluation of the affinity towards biological targets such as DNA (both calf thymus DNA and supercoiled plasmid DNA) and hydroxyapatite where the complexes showed a low DNA interaction, but a clear affinity for hydroxyapatite comparing to their precursors...
November 18, 2018: Journal of Inorganic Biochemistry
Sarah B Perl, Thomas G Merrill, Wilfredo Lopez, Mary T Bassett
We explore how a 1987 New York State court decision-Boreali v. Axelrod-affected public health rule-making nationally and, with considerable impact, locally in New York City (NYC). We discuss the history of the origin of the NYC Board of Health (BOH), and establish that legislatures can be challenging venues in which to enact public health-related laws. We describe how, as the NYC Department of Health and Mental Hygiene began to tackle modern public health problems (e.g., chronic diseases caused by food and tobacco), the regulatory power of its BOH was challenged...
November 29, 2018: American Journal of Public Health
Jennifer Townsend, Sara Keller, Martin Tibuakuu, Sameer Thakker, Bailey Webster, Maya Siegel, Kevin J Psoter, Omar Mansour, Trish M Perl
Background: In the United States, patients discharged on outpatient parenteral antimicrobial therapy (OPAT) are often treated by home health companies (HHCs) or skilled nursing facilities (SNFs). Little is known about differences in processes and outcomes between these sites of care. Methods: We performed a retrospective study of 107 patients with complicated Staphylococcus aureus infections discharged on OPAT from 2 academic medical centers. Clinical characteristics, site of posthospital care, process measures (lab test monitoring, clinic follow-up), adverse events (adverse drug events, Clostridium difficile infection, line events), and clinical outcomes at 90 days (cure, relapse, hospital readmission) were collected...
November 2018: Open Forum Infectious Diseases
Morgane Macheret, Thanos D Halazonetis
A better understanding of DNA replication initiation in human cells and how this process is altered upon DNA replication stress requires the ability to study origin firing genome wide. Previously described methods of mapping DNA replication origins in higher eukaryotes rely principally on fractionation of DNA fragments based on their size and, optionally, on the presence of ribonucleotides at their 5' end. Here, we describe a protocol for EdUseq-HU, a method for mapping early S-phase replication origins. Cells, synchronized by mitotic shake-off, are released in medium containing 5-ethynyl-2'-deoxyuridine (EdU; to label nascent DNA) and hydroxyurea (HU; to limit fork progression after origin firing)...
November 28, 2018: Nature Protocols
Ofer Yizhar-Barnea, Cristina Valensisi, Naresh Doni Jayavelu, Kamal Kishore, Colin Andrus, Tal Koffler-Brill, Kathy Ushakov, Kobi Perl, Yael Noy, Yoni Bhonker, Mattia Pelizzola, R David Hawkins, Karen B Avraham
The inner ear is a complex structure responsible for hearing and balance, and organ pathology is associated with deafness and balance disorders. To evaluate the role of epigenomic dynamics, we performed whole genome bisulfite sequencing at key time points during the development and maturation of the mouse inner ear sensory epithelium (SE). Our single-nucleotide resolution maps revealed variations in both general characteristics and dynamics of DNA methylation over time. This allowed us to predict the location of non-coding regulatory regions and to identify several novel candidate regulatory factors, such as Bach2, that connect stage-specific regulatory elements to molecular features that drive the development and maturation of the SE...
November 26, 2018: Scientific Reports
Axel Poulet, Ben Li, Tristan Dubos, Juan Carlos Rivera-Mulia, David M Gilbert, Zhaohui S Qin
Motivation: The replication timing (RT) program has been linked to many key biological processes including cell fate commitment, 3D chromatin organization and transcription regulation. Significant technology progress now allows to characterize the RT program in the entire human genome in a high-throughput and high-resolution fashion. These experiments suggest that RT changes dynamically during development in coordination with gene activity. Since RT is such a fundamental biological process, we believe that an effective quantitative profile of the local RT program from a diverse set of cell types in various developmental stages and lineages can provide crucial biological insights for a genomic locus...
November 22, 2018: Bioinformatics
Jing Zhu, Meili Lv, Nan Zhou, Dan Chen, Youjing Jiang, Li Wang, Wang He, Duo Peng, Zhilong Li, Shengqiu Qu, Yinji Wang, Hui Wang, Haibo Luo, Gang An, Weibo Liang, Lin Zhang
Microhaplotype markers are emerging forensic genetic markers that have received broad attention in forensics and may supplement existing genetic marker panels. Short tandem repeat polymorphisms (STRPs) and single nucleotide polymorphisms (SNPs) are the general genetic markers at present. Stutter and the high mutation rate of STR markers and the low polymorphism of SNP markers obstruct the solving of certain cases. Kidd proposed microhaplotype markers that encompass 2-4 SNPs. In this study, we screened microhaplotype loci through three criteria, and chose the Illumina® MiSeq platform to sequence the new markers...
November 16, 2018: Forensic Science International. Genetics
Sutthinee Wisutthathum, Céline Demougeot, Perle Totoson, Kannika Adthapanyawanich, Kornkanok Ingkaninan, Prapapan Temkitthawon, Krongkarn Chootip
BACKGROUND: Extract of the wild orchid, Eulophia macrobulbon (EM) inhibits phosphodiesterase5 (PDE5) suggesting it could preferentially dilate the pulmonary vasculature. PURPOSE AND STUDY DESIGN: To pharmacologically characterize the vascular actions of EM ethanolic extract and its active compound, 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol using isolated pulmonary arteries (PA) from rats having pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT)...
November 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
C T Yang, M Zuo, S J Wang, X Liu, R F Ma, Q Qi, H T Bi, Y M Li, G Z Zhang
OBJECTIVES: To observe the changes of the formation time of venous thrombus in rats, and to provide new ideas and methods for the estimation on thrombus formation time of the forensic cases died from thrombosis. METHODS: Totally 80 rats were randomly divided into 10 groups (0 h, 3 h, 6 h, 12 h, 1 d, 3 d, 1 week, 2 weeks, 3 weeks and 4 weeks after operation). A vein thrombosis model was established by the "narrow" method. The processes of thrombosis, organization, recanalization and the features of change on hemosiderin and calcium salt were observed by HE stain, Perls stain and Von Kossa stain...
August 2018: Fa Yi Xue za Zhi
Zach Rozenbaum, Yan Topilsky, Shafik Khoury, Milwidsky Assi, Asta Balchyunayte, Michal Laufer-Perl, Shlomo Berliner, David Pereg, Michal Entin-Meer, Ofer Havakuk
Studies performed in controlled laboratory conditions have shown that environmental thermal application may induce various circulatory changes. We aimed to demonstrate the effect of local climate on hemodynamics according to echocardiography . Echocardiographic studies conducted in ambulatory patients, 18 years of age or older, between January 2012 and July 2016 at our medical center were retrospectively included in case climate data on the day of the echocardiogram were available. Discomfort index, apparent temperature, temperature-humidity index, and thermal index were computed...
November 21, 2018: Journal of Applied Physiology
Hongyang Li, Shuai Hu, Nouri Neamati, Yuanfang Guan
Motivation: Combination therapy is widely used in cancer treatment to overcome drug resistance. High-throughput drug screening is the standard approach to study the drug combination effects, yet it becomes impractical when the number of drugs under consideration is large. Therefore, accurate and fast computational tools for predicting drug synergistic effects are needed to guide experimental design for developing candidate drug pairs. Results: Here, we present TAIJI, a high-performance software for fast and accurate prediction of drug synergism...
November 21, 2018: Bioinformatics
Paula Augusto Taunde, Matheus Viezzer Bianchi, Lívia Perles, Fernando Soares da Silva, Tainã Normanton Guim, Renan Alves Stadler, Marcos Rogério André, David Driemeier, Saulo Petinatti Pavarini
Avian malaria is a mosquito-borne disease that affects multiple avian species and is caused by protozoans of the genus Plasmodium. An avian malaria infection caused by Plasmodium sp. in Magellanic penguins (Spheniscus magellanicus) with high mortality is described in a zoo in Southern Brazil. Clinically, three birds presented signs of inappetence, anorexia, pale mucosa, dyspnea, and opisthotonus, with death in a clinical course of 5-8 h. At the necropsy, all birds exhibited pale mucosa, marked splenomegaly and hepatomegaly, in addition to moderate leptomeningeal blood vessels ingurgitation in the brain...
November 19, 2018: Parasitology Research
Sonia Medina, Ángel Gil-Izquierdo, Thierry Durand, Federico Ferreres, Raúl Domínguez-Perles
Structure-activity relationship (SAR) constitutes a crucial topic to discover new bioactive molecules. This approach initiates with the comparison of a target candidate with a molecule or a collection of molecules and their attributed biological functions to shed some light in the details of one or more SARs and subsequently using that information to outline valuable application of the newly identified compounds. Thus, while the empiric knowledge of medicinal chemistry is critical to these tasks, the results retrieved upon dedicated experimental demonstration retrieved resorting to modern high throughput analytical approaches and techniques allow to overwhelm the constraints adduced so far to the successful accomplishment of such tasks...
November 16, 2018: Antioxidants (Basel, Switzerland)
M Sobczak-Filipiak, T Męcik-Kronenberg, M Czopowicz, M Galanty, P Trębacz, J Frymus, I Badurek, J Szarek
Lipogranulomas are lesions found in histopathological liver examination in humans and in various animal species, including dogs, especially those with portosystemic shunts. They consist of macrophages and other inflammatory cells, and sometimes they contain iron salts (pigment granuloma). This study aimed at determining the number of granulomas and cellular composition of lipogranulomas in dogs with the congenital extrahepatic portosystemic shunt, and to identify factors associated with their development. 44 archival liver samples from dogs with portosystemic shunt were stained using HE, Perl's method and - in randomly-selected cases - immunohistochemically against CD56, CD20 and CD3 (DAKO)...
June 2018: Polish Journal of Veterinary Sciences
Jesús M Fernández-García, Paul J Evans, Samara Medina Rivero, Israel Fernandez, David García-Fresnadillo, Josefina Perles, Juan Casado, Nazario Martín
A geometrically-selective bottom-up synthesis of curved nanographenes is described. The synthetic methodology used involves the extension of the π-system of positively-curved corannulene by a [4+2] cycloaddition reaction followed by cyclodehydrogenation (Scholl oxidation). By selecting the conditions for the Scholl oxidation, the formation of a seven-membered ring that also confers negative curvature to the resulting nanographene can be activated offering two topologically distinct, curved nanographenes from a common precursor...
November 15, 2018: Journal of the American Chemical Society
Yan-Hang Gao, Jing-Yun Wang, Pei-Yan Liu, Jing Sun, Xiao-Mei Wang, Rui-Hong Wu, Xiu-Ting He, Zheng-Kun Tu, Chun-Guang Wang, Hong-Qin Xu, Jun-Qi Niu
AIM: To investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases. METHODS: This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed...
November 6, 2018: World Journal of Clinical Cases
Heather M Snyder, Roxana O Carare, Steven T DeKosky, Mony J de Leon, Derek Dykxhoorn, Li Gan, Raquel Gardner, Sidney R Hinds, Michael Jaffee, Bruce T Lamb, Susan Landau, Geoff Manley, Ann McKee, Daniel Perl, Julie A Schneider, Michael Weiner, Cheryl Wellington, Kristine Yaffe, Lisa Bain, Anthony M Pacifico, Maria C Carrillo
INTRODUCTION: In recent years, there has been growing discussion to better understand the pathophysiological mechanisms of traumatic brain injury and post-traumatic stress disorder and how they may be linked to an increased risk of neurodegenerative diseases including Alzheimer's disease in veterans. METHODS: Building on that discussion, and subsequent to a special issue of Alzheimer's & Dementia published in June 2014, which focused on military risk factors, the Alzheimer's Association convened a continued discussion of the scientific community on December 1, 2016...
November 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Perle Latré De Laté, Malak Haidar, Hifzur Ansari, Shahin Tajeri, Eszter Szarka, Anita Alexa, Kerry Woods, Attila Reményi, Arnab Pain, Gordon Langsley
Constitutive JNK activity characterizes bovine T and B cells infected with Theileria parva, and B cells and macrophages infected with T. annulata. Here, we show that T. annulata infection of macrophages manipulates JNK activation by recruiting JNK2 and not JNK1 to the parasite surface, whereas JNK1 is found predominantly in the host cell nucleus. At the parasite's surface JNK2 forms a complex with p104 a GPI-anchored T. annulata plasma membrane protein. Sequestration of JNK2 depended on PKA-mediated phosphorylation of a JNK-binding motif common to T...
November 9, 2018: Cellular Microbiology
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