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https://www.readbyqxmd.com/read/28644392/development-of-bone-targeting-drugs
#1
REVIEW
Molly Stapleton, Kazuki Sawamoto, Carlos J Alméciga-Díaz, William G Mackenzie, Robert W Mason, Tadao Orii, Shunji Tomatsu
The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca(2+)...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28644196/cebranopadol-a-novel-first-in-class-analgesic-drug-candidate-first-experience-in-patients-with-chronic-low-back-pain-in-a-randomized-clinical-trial
#2
Annette Christoph, Marie-Henriette Eerdekens, Maurits Kok, Gisela Volkers, Rainer Freynhagen
Chronic low back pain (LBP) is a common condition, usually with involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first Phase II, randomized, doubleblind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate to severe chronic LBP with and without neuropathic pain component...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28643100/perceived-devaluation-and-sti-testing-uptake-among-a-cohort-of-street-involved-youth-in-a-canadian-setting
#3
Mohammad Karamouzian, Jean Shoveller, Huiru Dong, Mark Gilbert, Thomas Kerr, Kora DeBeck
Perceived devaluation has been shown to have adverse effects on the mental and physical health outcomes of people who use drugs. However, the impact of perceived devaluation on sexually transmitted infections (STI) testing uptake among street-involved youth, who face multiple and intersecting stigmas due to their association with drug use and risky sexual practices, has not been fully characterized. Data were obtained between December 2013 and November 2014 from a cohort of street-involved youth who use illicit drugs aged 14-26 in Vancouver, British Columbia...
June 22, 2017: Archives of Sexual Behavior
https://www.readbyqxmd.com/read/28642041/interaction-of-polyhedral-oligomeric-silsesquioxanes-and-dipalmitoylphosphatidylcholine-at-the-air-water-interface-thermodynamic-and-rheological-study
#4
M Skrzypiec, G As Georgiev, M Rojewska, K Prochaska
Polyhedral oligomeric silsesquioxanes (POSS) derivatives containing open silsesquioxane cage bear great potential for biomedical applications and therefore their lateral interactions with phospholipids, major biomembranes and drug vehicles constituent, should be studied in detail. That is why the properties of surface films by two POSS-derivatives, POSS-polyethylene glycol (POSS-PEG) and POSS-perfluoroalkyl (POSS-OFP), pure and in presence of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) were studied using Langmuir surface balance...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641596/types-and-prevalence-of-extended-spectrum-beta-lactamase-producing-enterobacteriaceae-in-poultry
#5
Eva-Maria Saliu, Wilfried Vahjen, Jürgen Zentek
For several billion years, bacteria have developed mechanisms to resist antibacterial substances. In modern time, antibiotics are frequently used in veterinary and human medicine for prevention and treatment of diseases, globally still also for their growth promoting effects as feed additives. This complex situation has evolved in accelerating development and prevalence of multi-drug resistant bacteria in livestock and people. Extended-spectrum beta-lactamase (ESBL) producing bacteria are resistant to a wide range of ß-lactam antibiotics...
June 23, 2017: Animal Health Research Reviews
https://www.readbyqxmd.com/read/28641032/targeting-rho-gtpase-effector-p21-activated-kinase-4-pak4-suppresses-p-bad-microrna-drug-resistance-axis-leading-to-inhibition-of-pancreatic-ductal-adenocarcinoma-proliferation
#6
Ramzi M Mohammad, Yiwei Li, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Philip A Philip, Asfar S Azmi
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and therapy resistant malignancy. Mutant K-Ras, found in >90% of refractory PDAC, acts as a molecular switch activating Rho GTPase signaling that in turn promotes a plethora of pro-survival molecules and oncogenic microRNAs. We investigated the impact of Rho GTPase effector protein p21 activated kinase 4 (PAK4) inhibition on pro-survival p-Bad and oncogenic miRNA signaling. We demonstrate that the dual NAMPT and PAK4 modulators (KPT-9274 and KPT-9307) inhibit PDAC cell proliferation through down-regulation of Bad phosphorylation and up-regulation tumor suppressive miRNAs (miR-145, let-7c, let-7d, miR-34c, miR320 and miR-100)...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28640970/prevalence-of-new-psychoactive-substances-and-prescription-drugs-in-the-belgian-driving-under-the-influence-of-drugs-population
#7
S M R Wille, C Richeval, M Nachon-Phanithavong, J M Gaulier, V Di Fazio, L Humbert, N Samyn, D Allorge
Driving under the influence of drugs (DUID) is a worldwide problem. Several countries adopted DUID legislations which prove their deterrent effect and impact on road safety. However, use of new psychoactive substances (NPS) and prescription drugs is not known as the applied roadside screening tests are not yet adapted for these compounds. In this study, 558 blood samples obtained during roadside controls in Belgium (January to August 2015) after a positive Drugwipe 5S® test and 199 oral fluid (OF) samples obtained from negatively screened test pads were analyzed...
June 22, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28640948/high-level-%C3%AE-iii-tubulin-overexpression-occurs-in-most-head-and-neck-cancers-but-is-unrelated-to-clinical-outcome
#8
Julie C Nienstedt, Alexander Gröbe, Till Clauditz, Ronald Simon, Adrian Muenscher, Rainald Knecht, Guido Sauter, Christoph Moebius, Marco Blessmann, Max Heiland, Christina Pflug
BACKGROUND: βIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, the present study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC...
June 22, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28640746/a-chromosome-4-trisomy-contributes-to-increased-fluconazole-resistance-in-a-clinical-isolate-of-candida-albicans
#9
Matthew Z Anderson, Amrita Saha, Abid Haseeb, Richard J Bennett
Candida albicans is an important opportunistic fungal pathogen capable of causing both mucosal and disseminated disease. Infections are often treated with fluconazole, a front-line antifungal drug that targets the biosynthesis of ergosterol, a major component of the fungal cell membrane. Resistance to fluconazole can arise through a variety of mechanisms, including gain-of-function mutations, loss of heterozygosity events and aneuploidy. The clinical isolate P60002 was found to be highly resistant to azole-class drugs, yet lacked mutations or chromosomal rearrangements known to be associated with azole resistance...
June 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28639472/micrornas-as-a-tool-to-aid-stratification-of-colorectal-cancer-patients-and-to-guide-therapy
#10
Matthew Goblirsch, Georg Richtig, Ondrej Slaby, Ioana Berindan-Neagoe, Armin Gerger, Martin Pichler
Colorectal cancer is a common type of malignant disease with high rates of morbidity and mortality. Although treatment options have been expanded over the last years, the mainstay of curative treatment remains surgical removal of the tumor-bearing organ. Systemic treatment options include classic cytotoxic drugs as well as some biological agents. Noncoding RNAs are an evolving field in cancer diagnosis, prognosis and possible treatment. Noncoding miRNAs are small molecules with huge impact on gene expression...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28639058/geospatial-analysis-of-drug-poisoning-deaths-involving-heroin-in-the-usa-2000-2014
#11
Kathleen Stewart, Yanjia Cao, Margaret H Hsu, Eleanor Artigiani, Eric Wish
We investigate the geographic patterns of drug poisoning deaths involving heroin by county for the USA from 2000 to 2014. The county-level patterns of mortality are examined with respect to age-adjusted rates of death for different classes of urbanization and racial and ethnic groups, while rates based on raw counts of drug poisoning deaths involving heroin are estimated for different age groups and by gender. To account for possible underestimations in these rates due to small areas or small numbers, spatial empirical Baye's estimation techniques have been used to smooth the rates of death and alleviate underestimation when analyzing spatial patterns for these different groups...
June 21, 2017: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/28639034/ageing-health-status-and-coverage-rate-effects-on-community-prescription-costs-in-ireland
#12
Martin Kenneally, Brenda Lynch
AIMS AND OBJECTIVES: This paper aims to explore how GMS drug costs depend on age, gender, income, health status, community drug scheme coverage rates and whether they display significant differences across regions of Ireland. We also aim to find out whether the GMS drug costs of high and low income cohorts respond similarly to changes in their health status. The paper projects GMS drug costs in 2026 and examines the separate cost of population ageing and population growth over the period...
June 21, 2017: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
https://www.readbyqxmd.com/read/28638857/development-of-the-fda-tobacco-credibility-scale-fda-tcs
#13
Allison M Schmidt, Leah M Ranney, Seth M Noar, Adam O Goldstein
OBJECTIVES: Messages from organizations with high, compared to low, credibility may be more persuasive. Whereas the tobacco industry has long recognized the importance of credibility in promoting its messages and public image, the source credibility of key tobacco control organizations has gone largely unmeasured. To assess credibility of a key tobacco regulator, we developed a scale of the US Food and Drug Administration (FDA) tobacco-related credibility. METHODS: We developed and tested 30 items reflective of the dimensions of source credibility (trust, expertise, and public interest) and FDA's tobacco regulatory roles in a sample of 1353 US adults and assessed reliability and validity...
January 2017: Tobacco Regulatory Science
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#14
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638698/atypical-antipsychotic-therapy-in-parkinson-s-disease-psychosis-a-retrospective-study
#15
Mei Yuan, Laura Sperry, Norika Malhado-Chang, Alexandra Duffy, Vicki Wheelock, Sarah Farias, Kevin O'Connor, John Olichney, Kiarash Shahlaie, Lin Zhang
OBJECTIVE: Parkinson's disease psychosis (PDP) is a frequent complication of idiopathic Parkinson's disease (iPD) with significant impact on quality of life and association with poorer outcomes. Atypical antipsychotic drugs (APDs) are often used for the treatment of PDP; however, their use is often complicated by adverse drug reactions (ADRs). In this study, we present patients with PDP who were treated with the most commonly used atypical antipsychotic agents and review their respective ADRs...
June 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28635907/-the-problem-of-obstructive-sleep-apnea-syndrome-in-asthmatic-patients
#16
E G Sheludko, D E Naumov, Yu M Perelman, V P Kolosov
Asthma and obstructive sleep apnea syndrome (OSAS) are one of the most common chronic respiratory diseases. These have common risk factors that include obesity, gastroesophageal reflux disease (GERD) and impaired nasal breathing (allergic rhinitis, sinusitis). At the same time, experimental evidence demonstrates common pathophysiological mechanisms of these diseases, such as involvement in the process of the respiratory tract, a systemic inflammatory response, and implementation of neuromechanical reflexes...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#17
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28630205/the-impact-of-gyrb-and-eis-mutations-in-improving-second-line-drug-resistance-detection-among-mycobacterium-tuberculosis-isolates-from-georgia
#18
N Bablishvili, N Tukvadze, E Shashkina, B Mathema, N R Gandhi, H M Blumberg, R R Kempker
SETTING: The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB).OBJECTIVE: To evaluate whether the detection of mutations in gyrB and eis genes increased the sensitivity of detecting phenotypic resistance to ofloxacin and kanamycin or capreomycin as compared to use of the first generation MTBDRsl assay alone which evaluates for mutations in gyrA and rrs genes.DESIGN: A retrospective study of storedMycobacterium tuberculosis isolates. All isolates underwent DNA sequencing of resistance determining regions...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630195/topical-antimicrobial-treatments-can-elicit-shifts-to-resident-skin-bacterial-communities-and-reduce-colonization-by-staphylococcus-aureus-competitors
#19
Adam J SanMiguel, Jacquelyn S Meisel, Joseph Horwinski, Qi Zheng, Elizabeth A Grice
The skin microbiome is a complex ecosystem with important implications for cutaneous health and disease. Topical antibiotics and antiseptics are often employed to preserve the balance of this population, and inhibit colonization by more pathogenic bacteria. Despite their widespread use, however, the impact of these interventions on broader microbial communities remains poorly understood. Here we report the longitudinal effects of topical antibiotics and antiseptics on skin bacterial communities and their role in Staphylococcus aureus colonization resistance...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28629581/impact-of-a-teamstepps-trauma-nurse-academy-at-a-level-1-trauma-center
#20
V Kristen Peters, Ellen M Harvey, Andi Wright, Jennifer Bath, Dan Freeman, Bryan Collier
PROBLEM: Nurses are crucial members of the team caring for the acutely injured trauma patient. Until recently, nurses and physicians gained an understanding of leadership and supportive roles separately. With the advent of a multidisciplinary team approach to trauma care, formal team training and simulation has transpired. METHODS: Since 2007, our Level I trauma system has integrated TeamSTEPPS (Team Strategies & Tools to Enhance Performance & Patient Safety; Agency for Healthcare Research and Quality, Rockville, MD) into our clinical care, joint training of nurses and physicians, using simulations with participation of all health care providers...
June 16, 2017: Journal of Emergency Nursing: JEN: Official Publication of the Emergency Department Nurses Association
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