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Abdulkadir Kocak, Ismail Erol, Muslum Yildiz, Hatice Can
Developing small compound based drugs targeting the β-secretase (BACE) enzyme is one of the most promising strategies in treatment of the Alzheimer's disease. As the enzyme shows the activity based on the acid-base reaction at a very narrow pH range, the protonation state of aspartic acids with the residue number 32 and 228 (Asp32 and Asp228), which forms the active site dyad, along with the protonation state of the ligand (substrate or inhibitor) play very critical role in interactions between the ligand and enzyme...
October 17, 2016: Journal of Molecular Graphics & Modelling
Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Qinghua Chen, Lulu Zhang, Siyao Chen, Yaqian Huang, Kun Li, Xiaoqi Yu, Huijuan Wu, Xiaoyu Tian, Chunyu Zhang, Chaoshu Tang, Junbao Du, Hongfang Jin
BACKGROUND: The study was designed to investigate if endogenous sulfur dioxide (SO2) was involved in cardiomyocyte autophagy and myocardial hypertrophy stimulated by angiotensin II (Ang II). METHODS: Thirty-two C57 mice were randomly divided into control, SO2, Ang II and Ang II+SO2 groups. Human myocardial cell line H9c2 was divided into four groups including control, SO2, Ang II and Ang II+SO2 groups. Blood pressure and myocardial hypertrophy of the mice were measured two weeks after Ang II administration...
September 30, 2016: International Journal of Cardiology
Felix Stibany, Stine Nørgaard Schmidt, Andreas Schäffer, Philipp Mayer
The aims of the present study were (1) to develop a passive dosing approach for aquatic toxicity testing of liquid substances with very high Kow values and (2) to apply this approach to the model substance dodecylbenzene (DDB, Log Kow = 8.65). The first step was to design a new passive dosing format for testing DDB exactly at its saturation limit. Silicone O-rings were saturated by direct immersion in pure liquid DDB, which resulted in swelling of >14%. These saturated O-rings were used to establish and maintain DDB exposure exactly at the saturation limit throughout 72-h algal growth inhibition tests with green algae Raphidocelis subcapitata...
October 18, 2016: Chemosphere
Margret Thorsteinsdottir, Unnur A Thorsteinsdottir, Finnur F Eiriksson, Hrafnhildur L Runolfsdottir, Inger M Sch Agustsdottir, Steinunn Oddsdottir, Baldur B Sigurdsson, Hordur K Hardarson, Nilesh R Kamble, Snorri Th Sigurdsson, Vidar O Edvardsson, Runolfur Palsson
Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA...
September 14, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Lotte H J M Lemmens, Viola N L S Müller, Arnoud Arntz, Marcus J H Huibers
We present a systematic empirical update and critical evaluation of the current status of research aimed at identifying a variety of psychological mediators in various forms of psychotherapy for depression. We summarize study characteristics and results of 35 relevant studies, and discuss the extent to which these studies meet several important requirements for mechanism research. Our review indicates that in spite of increased attention for the topic, advances in theoretical consensus about necessities for mechanism research, and sophistication of study designs, research in this field is still heterogeneous and unsatisfactory in methodological respect...
September 20, 2016: Clinical Psychology Review
Yong-Jun Ye, Xin-Tao Dai, De-Xin Ding, Ya-Li Zhao
In this study, a one-dimensional steady-state mathematical model of radon transport in fragmented uranium ore was established according to Fick's law and radon transfer theory in an air-water interface. The model was utilized to obtain an analytical solution for radon concentration in the air-water, two-phase system under steady state conditions, as well as a corresponding radon exhalation rate calculation formula. We also designed a one-dimensional experimental apparatus for simulating radon diffusion migration in the uranium ore with various water levels to verify the mathematical model...
October 19, 2016: Journal of Environmental Radioactivity
Karen P Hayhurst, Matthias Pierce, Matthew Hickman, Toby Seddon, Graham Dunn, John Keane, Tim Millar
BACKGROUND: Although evidence points to a strong link between illicit drug use and crime, robust evidence for temporal order in the relationship is scant. We carried out a systematic review to assess the evidence for pathways through opiate/crack cocaine use and offending to determine temporal order. METHODS: A systematic review sourced five databases, three online sources, bibliographies and citation mapping. Inclusion criteria were: focus on opiate/crack use, and offending; pre-drug use information; longitudinal design; corroborative official crime records...
October 19, 2016: International Journal on Drug Policy
Linda Rothman, Andrew Howard, Ron Buliung, Colin Macarthur, Sarah A Richmond, Alison Macpherson
BACKGROUND: Child pedestrian-motor vehicle collisions (PMVCs) have decreased in Canada in the past 20 years. Many believe this trend is explained by the rise in automobile use for all travel. Initiatives to increase walking to school need to consider PMVC risk. Potential risk factors related to walking to school, the built environment and social factors were examined for schools with historically high child PMVC rates. METHODS: Child PMVCs (age 4-12 years) from 2000 to 2013 and built environment features were mapped within school attendance boundaries in the City of Toronto, Canada...
October 19, 2016: Accident; Analysis and Prevention
Jie Wang, Helai Huang, Qiang Zeng
OBJECTIVES: This paper aimed to (i) differentiate the effects of contributory factors on crash risks related to different transportation modes, i.e., motor vehicle, bicycle and pedestrian; (ii) explore the potential contribution of zone-level factors which are traditionally excluded or omitted, so as to track the source of heterogeneous effects of certain risk factors in crash-frequency models by different modes. METHODS: Two analytical methods, i.e. negative binomial models (NB) and random parameters negative binomial models (RPNB), were employed to relate crash frequencies of different transportation modes to a variety of risk factors at intersections...
October 19, 2016: Accident; Analysis and Prevention
Tahereh Zargar, Taghi Khayamian, Mohammad T Jafari
A selective thin-film microextraction based on aptamer immobilized on cellulose paper was used as a paper spray ionization source for ion mobility spectrometry (PSI-IMS), for the first time. In this method, the paper is not only used as an ionization source but also it is utilized for the selective extraction of analyte, based on immobilized aptamer. This combination integrates both sample preparation and analyte ionization in a Whatman paper. To that end, an appropriate sample introduction system with a novel design was constructed for the paper spray ionization source...
October 17, 2016: Journal of Pharmaceutical and Biomedical Analysis
Elizabeth Hammond, Emma Shu, Karagin Sawchuk, Yvonne Myal, Afshin Raouf, Thomas Klonisch, Sabine Hombach-Klonisch, Etienne Leygue, Sam Kung, Janice Safneck, Michael Mowat, Wayne Xu, Leigh Murphy, Marshall Pitz
BACKGROUND: Few descriptive epidemiological studies on the incidence, treatment and survival can accurately reflect a whole population. Manitoba, Canada has an accurate cancer registry, a drug information program network and a breast screening program since 1995. This combined with a stable population provides true population data that can accurately describe the region. METHODS: Using a retrospective cohort design all Breast Cancer cases were obtained from 2004-2010 (N=5399) and grouped by Intrinsic sub-type...
October 19, 2016: Cancer Epidemiology
K Holstein, A Batorova, M Carvalho, K Fijnvandraat, P Holme, K Kavakli, T Lambert, A Rocino, V Jiménez-Yuste, J Astermark
INTRODUCTION: Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician. OBJECTIVES: To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice...
October 15, 2016: Thrombosis Research
Sunil Nath
As the chief energy source of eukaryotic cells, it is important to determine the thermodynamic efficiency of ATP synthesis in oxidative phosphorylation (OX PHOS). Previous estimates of the thermodynamic efficiency of this vital process have ranged from Lehninger's original back-of-the-envelope calculation of 38% to the often quoted value of 55-60% in current textbooks of biochemistry, to high values of 90% from recent information theoretic considerations, and reports of realizations of close to ideal 100% efficiencies by single molecule experiments...
October 15, 2016: Biophysical Chemistry
Carol Chu, Melanie A Hom, Megan L Rogers, Ian H Stanley, Fallon B Ringer-Moberg, Matthew C Podlogar, Jameson K Hirsch, Thomas E Joiner
BACKGROUND: Insomnia is a robust correlate of suicidal ideation and behavior. Preliminary research has identified thwarted belongingness (c.f. social disconnection) as an explanatory link between insomnia and suicidal ideation. OBJECTIVES: This study replicates and extends previous findings using both cross-sectional and longitudinal designs in four demographically diverse samples. Additionally, the specificity of thwarted belongingness was evaluated by testing anxiety as a rival mediator...
October 11, 2016: Journal of Affective Disorders
Nancy M Lee, Cevat Erisken, Thomas Iskratsch, Michael Sheetz, William N Levine, Helen H Lu
Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics critical for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation...
October 12, 2016: Biomaterials
Teresa V Mitchell
Deafness is known to affect processing of visual motion and information in the visual periphery, as well as the neural substrates for these domains. This study was designed to characterize the effects of early deafness and lifelong sign language use on visual category sensitivity of the N170 event-related potential. Images from nine categories of visual forms including upright faces, inverted faces, and hands were presented to twelve typically hearing adults and twelve adult congenitally deaf signers. Classic N170 category sensitivity was observed in both participant groups, whereby faces elicited larger amplitudes than all other visual categories, and inverted faces elicited larger amplitudes and slower latencies than upright faces...
October 19, 2016: Hearing Research
M David Keller, John M Ziriax, William Barns, Benjamin Sheffield, Douglas Brungart, Tony Thomas, Bobby Jaeger, Kurt Yankaskas
Noise, hearing loss, and electronic signal distortion, which are common problems in military environments, can impair speech intelligibility and thereby jeopardize mission success. The current study investigated the impact that impaired communication has on operational performance in a command and control environment by parametrically degrading speech intelligibility in a simulated shipborne Combat Information Center. Experienced U.S. Navy personnel served as the study participants and were required to monitor information from multiple sources and respond appropriately to communications initiated by investigators playing the roles of other personnel involved in a realistic Naval scenario...
October 19, 2016: Hearing Research
Bangrong Cai, Aimei Liao, Kyung-Ku Lee, Jae-Sam Ban, Hyun-Sam Yang, Young Jun Im, ChangJu Chun
A series of methotrexate-diosgenin conjugates was designed and synthesized to enhance the passive internalization of methotrexate (MTX) into transport-resistant cells. The inhibitory effects of these conjugates on dihydrofolate reductase (DHFR), and their anti-proliferation behaviors against a transport-resistant breast cancer cell line, MDA-MB-231, were investigated. All of the synthesized conjugates retained an ability to inhibit DHFR after the diosgenin substitution. The MTX conjugates were much more potent against methotrexate-resistant MDA-MB-231 cells than MTX...
October 19, 2016: Steroids
C Teljeur, P S Moran, S Walshe, S M Smith, F Cianci, L Murphy, P Harrington, M Ryan
AIMS: To systematically review the evidence on the costs and cost-effectiveness of self-management support interventions for people with diabetes. BACKGROUND: Self-management support is the provision of education and supportive interventions to increase patients' skills and confidence in managing their health problems, potentially leading to improvements in HbA1c levels in people with diabetes. METHODS: Randomized controlled trials, observational studies or economic modelling studies were eligible for inclusion in the review...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
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