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Ghaith Altawallbeh, Laura Smith, Stephen J Lewis, Simon Authier, Kim Bujold, Benjamin Gaston, Ilya Bederman
CONTEXT: Sudaxine is a novel respiratory stimulant that increases ventilatory drive via NO+ -thiolate signaling and is under development for reversal of opioid-induced respiratory depression and other critical care indications. OBJECTIVE: This study investigates the pharmacokinetic characteristics after intravenous administration of Sudaxine by using a simple LC-MS/MS method. MATERIALS AND METHODS: A sensitive LC-MS/MS method was validated to determine the concentration of Sudaxine in beagle dog plasma after intravenous administration of Sudaxine at (3, 10, 30 and 100 mg/kg)...
September 22, 2018: Drug Testing and Analysis
Xialiang Li, Haitao Lei, Jieyu Liu, Xueli Zhao, Shuping Ding, Zongyao Zhang, Xixi Tao, Wei Zhang, Weichao Wang, Xiaohong Zheng, Rui Cao
Water splitting is promising to realize a hydrogen-based society. The practical use of molecular water splitting catalysts relies on their integration onto electrode materials. We describe here the immobilization of Co corroles on carbon nanotubes (CNTs) by four strategies and compare the performance of the resulted hybrids for H2 and O2 evolution. Co corroles can be covalently attached to CNTs with short conjugated linkers (the hybrid is denoted as H1) or with long alkane chains (H2), or can be grafted to CNTs via strong π-π interactions (H3) or via simple adsorption (H4)...
September 22, 2018: Angewandte Chemie
Anne E Kazak, Michele A Scialla, Andrea F Patenaude, Kimberly Canter, Anna C Muriel, Mary Jo Kupst, Fang Fang Chen, Lori Wiener
OBJECTIVE: This paper presents data on licensure/certification status, supervision of multidisciplinary pediatric psychosocial staff, and training opportunities in pediatric cancer programs in the United States (U.S.), data that is critical to provide care aligned with the Standards of Psychosocial Care in Pediatric Cancer (Psychosocial Standards). METHODS: An online survey of psychosocial care consistent with the Psychosocial Standards was completed from a national sample of pediatric cancer programs (144/200)...
September 22, 2018: Psycho-oncology
Vincenzo Carbone, Linley R Schofield, Carrie Sang, Andrew J Sutherland-Smith, Ron S Ronimus
The crystal structure of UDP-N-acetylglucosamine 4-epimerase (UDP-GlcNAc 4-epimerase; WbpP; EC, from the archaeal methanogen Methanobrevibacter ruminantium strain M1, was determined to a resolution of 1.65 Å. The structure, with a single monomer in the crystallographic asymmetric unit, contained a conserved N-terminal Rossmann fold for nucleotide binding and an active site positioned in the C-terminus. UDP-GlcNAc 4-epimerase is a member of the short-chain dehydrogenases/reductases superfamily, sharing sequence motifs and structural elements characteristic of this family of oxidoreductases and bacterial 4-epimerases...
September 22, 2018: Proteins
Sushma Yadav, Claudia M Kowolik, Min Lin, Darren Zuro, Susanta K Hui, Arthur D Riggs, David A Horne
Prostate cancer is one of the most commonly diagnosed cancers and a pressing health challenge in men worldwide. Radiation therapy (RT) is widely considered a standard therapy advanced as well as localised prostate cancer. Although this primary therapy is associated with high cancer control rates, up to one third of patients undergoing radiation therapy becomes radio-resistant and/or has tumor-relapse/recurrence. Therefore, focus on new molecular targets and pathways is essential to develop novel radio-sensitizing agents for the effective and safe treatment of prostate cancer...
September 22, 2018: Molecular Carcinogenesis
Ruiqi Zhu, Wenyi Lin, Weiwei Zhao, Fengjuan Fan, Liang Tang, Yu Hu
Acute myeloid leukemia (AML) is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs (miRNAs) play a critical role in AML diagnosis, pathogenesis, and prognosis of AML. Little has been done to identify a miRNA signature in pediatric and adolescent patients for predicting overall survival. This study aims to identify a panel of miRNA signature that could predict the prognosis of all younger AML patients with all subtypes of AML by analyzing data from The Cancer Genome Atlas (TCGA). A total of 229 patients under 23 years with miRNA data and corresponding clinical data from TCGA database were enrolled in this study...
September 22, 2018: Journal of Cellular Biochemistry
Hsueh-Chun Wang, Shau-Ku Huang
Metformin, an anti-diabetic drug, possesses anti-inflammatory property beyond its glucose-lowering activity, but its regulatory effect on mast cells and allergic responses remains unknown, wherein the aryl hydrocarbon receptor (AhR)-ligand axis is critical in controlling mast cell activation. Herein, we provide evidence supporting the role of metformin in modulating mast cell activation by FcεR1-, AhR-mediated signaling or their combination. Metformin at relatively low doses was shown to suppress FcεR1-mediated degranulation, IL-13, TNF-α and sphingosine-1-phosphate (S1P) secretion in murine bone marrow-derived mast cells (BMMCs)...
September 22, 2018: European Journal of Immunology
Jakub Fronczek, Kamil Jurand Polok, Ilona Nowak-Kózka, Anna Włudarczyk, Jacek Górka, Mirosław Czuczwar, Paweł Krawczyk, Mirosław Ziętkiewicz, Łukasz R Nowak, Maciej Żukowski, Katarzyna Kotfis, Katarzyna Cwyl, Ryszard Gajdosz, Romuald Bohatyrewicz, Jowita Biernawska, Paweł Grudzień, Paweł Nasiłowski, Natalia Popek, Waldemar Cyrankiewicz, Katarzyna Wawrzyniak, Marek Wnuk, Dariusz Maciejewski, Dorota Studzińska, Szymon Bernas, Mariusz Piechota, Waldemar Machała, Marta Serwa, Maria Wujtewicz, Jan Stefaniak, Małgorzata Szymkowiak, Ryszard Gawda, Barbara Adamik, Natalia Kozera, Waldemar Goździk, Hans Flaatten, Wojciech Szczeklik
BACKGROUND: The increasing population of very old intensive care patients (VIPs) is a major challenge currently faced by clinicians and policymakers. Reliable indicators of VIPs' prognosis and purposefulness of their admission to the intensive care unit (ICU) are urgently needed. METHODS: This is a report from the Polish sample of the VIP1 multicentre cohort study (NCT03134807). Patients ≥ 80 years of age admitted to the ICU were included in the study. Information on the type and reason for admission, demographics, utilisation of ICU procedures, ICU length of stay, organ dysfunction and the decision to apply end-of-life care was collected...
September 22, 2018: Anaesthesiology Intensive Therapy
Tomasz Jasiński, Radosław Owczuk, Magdalena Wujtewicz
BACKGROUND: Salbutamol is a short acting beta-2 mimetic commonly used among intensive care unit patients. There are data suggesting that his mechanism of action can be a potential factor triggering arrhythmias. The aim of this study was to assess whether nebulized salbutamol causes systemic effects resulting in electrocardiographic alterations associated with atrial fibrillation occurrence in mechanically ventilated patients. METHODS: 50 individuals were randomly allocated to receive either 2...
September 22, 2018: Anaesthesiology Intensive Therapy
(no author information available yet)
BACKGROUND: Although oversedation has been associated with increased morbidity in ventilated critically ill patients, it is unclear whether prevention of oversedation improves mortality. We aimed to assess 90-day mortality in patients receiving a bundle of interventions to prevent oversedation as compared to usual care. METHODS: In this randomized multicentre trial, all adult patients requiring mechanical ventilation for more than 48 h were included. Two groups were compared: patients managed according to usual sedation practices (control), and patients receiving sedation according to an algorithm which provided a gradual multilevel response to pain, agitation, and ventilator dyssynchrony with no specific target to alter consciousness and no use of sedation scale and promoted the use of alternatives to continuous infusion of midazolam or propofol (intervention)...
September 21, 2018: Annals of Intensive Care
Sebastian Ocklenburg, Catrona Anderson, Wanda M Gerding, Christoph Fraenz, Caroline Schlüter, Patrick Friedrich, Maximilian Raane, Burkhard Mädler, Lara Schlaffke, Larissa Arning, Jörg T Epplen, Onur Güntürkün, Christian Beste, Erhan Genç
Myelination of axons in the central nervous system is critical for human cognition and behavior. The predominant protein in myelin is proteolipid protein-making PLP1, the gene that encodes for proteolipid protein, one of the primary candidate genes for white matter structure in the human brain. Here, we investigated the relation of genetic variation within PLP1 and white matter microstructure as assessed with myelin water fraction imaging, a neuroimaging technique that has the advantage over conventional diffusion tensor imaging in that it allows for a more direct assessment of myelin content...
September 21, 2018: Molecular Neurobiology
Beth H Rice Bradley
PURPOSE OF REVIEW: It is estimated that over 400 million people worldwide are living with diabetes. Excess adiposity is the strongest risk factor for non-insulin-dependent diabetes, type 2. Lifestyle interventions have demonstrated that diet plays a critical role in preventing the onset of type 2 diabetes. Dietary fat is not only a source of energy and nutrients, but also bioactive fatty acids. The purpose of this review was to examine data from recent prospective cohort studies and dietary interventions to determine if there are benefits to fat consumption on diabetes risk...
September 21, 2018: Current Nutrition Reports
Amit Fulzele, Eric J Bennett
Protein ubiquitylation is one of the most prevalent posttranslational modifications (PTM) within cells. Ubiquitin modification of target lysine residues typically marks substrates for proteasome-dependent degradation. However, ubiquitylation can also alter protein function through modulation of protein complexes, localization, or activity, without impacting protein turnover. Taken together, ubiquitylation imparts critical regulatory control over nearly every cellular, physiological, and pathophysiological process...
2018: Methods in Molecular Biology
Spencer Hill, Connor Hill, Gary Kleiger
Ubiquitin ligases (E3s) function by binding to both a protein substrate and to ubiquitin-conjugating enzymes (E2s) bound to ubiquitin. E3s facilitate the transfer of ubiquitin from the E2 active site to an E3-bound substrate. Thus, the affinity of the interaction of an E2 with its E3 partner is of considerable interest. The purpose of this work is to (1) provide protocols for the purification of the human E2 Cdc34, as well as for some additional protein components needed for the assays described here whose purification protocols haven't been described elsewhere in detail; (2) provide the researcher with critical information regarding the proper long-term storage of these enzymes to retain maximal activity; (3) provide a protocol to benchmark Cdc34 activity with previously described activity levels in the literature; and (4) provide a simple and rapid means of measuring E2 affinity for an E3...
2018: Methods in Molecular Biology
Qiong Wang, Cheng-Yu Chung, Julian N Rosenberg, Geng Yu, Michael J Betenbaugh
Genetic engineering plays an essential role in the development of cell lines for biopharmaceutical manufacturing. Advanced gene editing tools can improve both the productivity of recombinant cell lines as well as the quality of therapeutic antibodies. Antibody glycosylation is a critical quality attribute for therapeutic biologics because the glycan patterns on the antibody fragment crystallizable (Fc) region can alter its clinical efficacy and safety as a therapeutic drug. As an example, recombinant antibodies derived from Chinese hamster ovary (CHO) cells are generally highly fucosylated; the absence of fucose significantly enhances antibody dependent cell-mediated cytotoxicity (ADCC) against cancer cells...
2018: Methods in Molecular Biology
Sufeng Wang, Shuang Qiu, Shijian Ge, Jia Liu, Zhanglin Peng
The environmental-economic focus of wastewater treatment and management attracts growing attentions in recent years. The static efficiencies and their dynamic changes are helpful to systematically assess the environmental performance of the water agencies and wastewater treatment plants (WWTPs). Additionally, identifying key factors of efficiencies is critical to improve the operation of WWTPs. In this study, the window method of data envelopment analysis (DEA) was applied to estimate the annual efficiency for four Canadian WWTPs and to explore the variations of annual efficiency under different window lengths...
September 21, 2018: Environmental Science and Pollution Research International
Francesca Becherini, Caterina Durante, Elsa Bourguignon, Mario Li Vigni, Vincent Detalle, Adriana Bernardi, Patrizia Tomasin
BACKGROUND AND METHODS: Wall paintings and architectural surfaces in outdoor environments are exposed to several physical, chemical and biological agents, hence they are often treated with different products to prevent or slow down their deterioration. Among the factors that have to be taken into account in the selection of the most suitable treatment for decorated surfaces, the aesthetic compatibility with the substrate is of great importance in the cultural heritage field; minimizing colour variation after treatment application is a crucial issue in particular for painted surfaces...
September 21, 2018: Chemistry Central Journal
Alain Nathan Sahin, Anne Sarah Sahin, Frank Schwenter, Herawaty Sebajang
YouTube is the second most visited website in the world. No studies to date have characterized and evaluated YouTube videos on colorectal cancer (CRC) although these videos could influence patient decision-making, notably regarding screening and prevention. This study aims to report the characteristics and quality of these videos as patient education resources for CRC. YouTube's search engine was queried with different search phrases relating to CRC. The first two pages of each search result were analyzed. Two specialists devised a critical appraisal tool with a list of criteria to assess the videos...
September 21, 2018: Journal of Cancer Education: the Official Journal of the American Association for Cancer Education
Ying Zhang, Jacques Vanneste, Jiaxin Xu, Xiaoxing Liu
Currently, a high percentage of China's households face financial catastrophe as a direct result of excessive out-of-pocket (OOP) health expenditures. To alleviate this, China has set up the Critical Illness Insurance (CII) program since 2012. However, the current CII is still in an experimental phase and tested in 8 (out of 34) provinces, which has not been proved to be effective. This paper develops a health financing system for reducing catastrophic medical spending using a two-layer model for CII. This model partly compensates expenses exceeding the cap line of the Social Resident Basic Medical Insurance scheme to maintain the ratio of OOP expenses to total medical expenditure approximately at 20%...
September 21, 2018: International Journal of Health Economics and Management
D García-Azorin, N Yamani, L M Messina, I Peeters, M Ferrili, D Ovchinnikov, M L Speranza, V Marini, A Negro, S Benemei, M Barloese
BACKGROUND: Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review. METHODS: We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline...
September 21, 2018: Journal of Headache and Pain
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