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https://www.readbyqxmd.com/read/28922811/a-programme-to-create-short-course-chemotherapy-for-pulmonary-mycobacterium-avium-disease-based-on-pharmacokinetics-pharmacodynamics-and-mathematical-forecasting
#1
Devyani Deshpande, Shashikant Srivastava, Tawanda Gumbo
Objectives: Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. Methods: We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922810/a-shock-and-awe-thioridazine-and-moxifloxacin-combination-based-regimen-for-pulmonary-mycobacterium-avium-intracellulare-complex-disease
#2
Shashikant Srivastava, Devyani Deshpande, Carleton M Sherman, Tawanda Gumbo
Objectives: To develop a thioridazine/moxifloxacin-based combination regimen for treatment of pulmonary infection due to Mycobacterium avium-intracellulare complex (MAC) that kills bacteria faster than the standard treatment regimen. Methods: Monocytes were infected with MAC and inoculated into the hollow-fibre system model for pulmonary MAC disease (HFS-MAC). We co-administered ethambutol plus azithromycin daily for 28 days, to achieve the same human concentration-time profiles that result from standard doses, in three HFS-MAC systems...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#3
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922808/the-discovery-of-ceftazidime-avibactam-as-an-anti-mycobacterium-avium-agent
#4
Devyani Deshpande, Shashikant Srivastava, Moti L Chapagain, Pooi S Lee, Kayle N Cirrincione, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To determine if ceftaroline and ceftazidime combined with avibactam are efficacious against pulmonary Mycobacterium avium complex (MAC) disease. Methods: First, we performed a concentration-effect study of ceftaroline and ceftaroline/avibactam against extracellular MAC in test tubes. Given the difficulty of obtaining avibactam at the time of experimentation, we used a single concentration of commercial ceftazidime/avibactam, and two sets of non-treated controls, one with ceftazidime/avibactam and the other without...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922807/tedizolid-is-highly-bactericidal-in-the-treatment-of-pulmonary-mycobacterium-avium-complex-disease
#5
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. Methods: We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922805/failure-of-the-azithromycin-and-ethambutol-combination-regimen-in-the-hollow-fibre-system-model-of-pulmonary-mycobacterium-avium-infection-is-due-to-acquired-resistance
#6
Shashikant Srivastava, Devyani Deshpande, Tawanda Gumbo
Objectives: To investigate the performance of the two backbone drugs in the standard combination therapy regimen in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) infection. Methods: Six HFS were inoculated with human-derived monocytes infected with MAC, and treated with 15 mg/kg of ethambutol and 500 mg of azithromycin daily for 28 days to recapitulate the concentration-time profiles seen in the lungs of humans treated with these drugs and doses...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922803/micropredator-niche-differentiation-between-bulk-soil-and-rhizosphere-of-an-agricultural-soil-depends-on-bacterial-prey
#7
Lu Zhang, Tillmann Lueders
Predation is a fundamental mechanism of all food webs, but its drivers and organismic connectivities, especially at microbial level, are still poorly understood. Specifically, competitive carbon flows in the presence of multiple micropredators, as well as trophic links within and between microbial kingdoms have rarely been resolved. Here, using maize-planted agricultural soil as a model system, we have investigated the predation of amended bacterial prey by both prokaryotic and eukaryotic micropredators. We have queried how soil compartment (rhizosphere vs bulk soil) and nature of prey (Gram-positive vs Gram-negative) influence predation outcomes...
September 1, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28922741/genomic-and-biochemical-characterization-of-sialic-acid-acetylesterase-siae-in-zebrafish
#8
Viola Ravasio, Eufemia Damiati, Daniela Zizioli, Flavia Orizio, Edoardo Giacopuzzi, Marta Manzoni, Roberto Bresciani, Giuseppe Borsani, Eugenio Monti
Sialic acid acetylesterase (SIAE) removes acetyl moieties from the carbon 9 and 4 hydroxyl groups of sialic acid and recently a debate has been opened on its association to autoimmunity. Trying to get new insights on this intriguing enzyme we have studied siae in zebrafish (Danio rerio). In this teleost siae encodes for a polypeptide with a high degree of sequence identity to human and mouse counterparts. Zebrafish Siae behavior upon transient expression in COS7 cells is comparable to human enzyme concerning pH optimum of enzyme activity, subcellular localization and glycosylation...
October 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28922732/physcion-8-o-%C3%AE-glucopyranosideregulates-cell-cycle-apoptosis-and-invasion-in-glioblastoma-cells-through-modulating-skp2
#9
Wen Li, Fuxia Li, Yanfang Zhu, Daqing Song
Glioblastoma multiforme (GBM) is the most common malignant glioma in the central nervous system. This study aimed to investigate the anti-tumor activity of physcion 8-O-β-glucopyranoside (PG) in GBM cells. This showed that PG could significantly block cell cycle progression, induce apoptosis, and suppress invasion in both model GBM cell lines (U87 and U251). At the molecular level, PG repressed the expression of S-phase kinase protein 2 (Skp2), which was responsible for the anti-tumor effect of PG in GBM cells...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922718/tanshinone-iia-protects-against-chronic-intermittent-hypoxia-induced-myocardial-injury-via-activating-the-endothelin-1-pathway
#10
Na Wang, Yue Chang, Lingling Chen, Ya-Jing Guo, Ya-Shuo Zhao, Qiu-Hong Guo, En-Sheng Ji
Tanshinone IIA (Tan IIA) may exert significant protective effects against heart oxidative stress damage in obstructive sleep apnoea (OSA) syndrome. Chronic intermittent hypoxia (CIH)-triggered left ventricular dysfunction is used in a rat model to mimic CIH in OSA patients. 48 rats were randomly divided into three groups: normal control (NC) group, CIH group and CIH+Tan IIA group with 16 rats in each group. At the end of experiment (day 21), the blood pressure, Plasma ET-1 and NO content, hemodynamic indexes, heart histology, myocardial apoptosis as well as the expression of eNOS, ET-1, ETA receptor and ETB receptor were compared among different groups...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922716/quaternary-ammonium-groups-modified-starch-microspheres-for-instant-hemorrhage-control
#11
Fangping Chen, Xiaoyan Cao, Junxia Yu, Huantong Su, Shuda Wei, Hua Hong, Changsheng Liu
Instant rapid hemostasis is crucial not only for decreasing mortality in these conditions, but also for optimal recovery. The hemostatic agents on the market suffer from inefficiency hemostasis, nondegradability, high cost and potential safety issues. It is necessary to develop a hemostatic agent with rapid hemostatic performance, potent biodegradation and improved biocompatibility. The aim of this work was to develop a novel type of cationic modified starch microspheres (CS) and investigate its hemostatic performance...
August 24, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28922664/patchy-particles-made-by-colloidal-fusion
#12
Zhe Gong, Theodore Hueckel, Gi-Ra Yi, Stefano Sacanna
Patches on the surfaces of colloidal particles provide directional information that enables the self-assembly of the particles into higher-order structures. Although computational tools can make quantitative predictions and can generate design rules that link the patch motif of a particle to its internal microstructure and to the emergent properties of the self-assembled materials, the experimental realization of model systems of particles with surface patches (or 'patchy' particles) remains a challenge. Synthetic patchy colloidal particles are often poor geometric approximations of the digital building blocks used in simulations and can only rarely be manufactured in sufficiently high yields to be routinely used as experimental model systems...
September 18, 2017: Nature
https://www.readbyqxmd.com/read/28922654/student-s-perception-about-innovative-teaching-learning-practices-in-forensic-medicine
#13
Sanjay Gupta, Utsav N Parekh, Jaishree D Ganjiwale
BACKGROUND: Since decades, Forensic Medicine is mainly taught by didactic methods but in last couple of years some other teachinglearning and assessment methods are also introduced at some places which also lacks uniformity. Feedback from learners is most fundamental aspect to assess effectiveness of applied methods, but is not implemented in practice at most medical schools in India. Unfortunately, medical students are deprived of this practical empowerment and thus may not be efficient enough to contribute potentially to the justice system during their professional life...
September 11, 2017: Journal of Forensic and Legal Medicine
https://www.readbyqxmd.com/read/28922651/evaluating-the-effect-of-smoking-cessation-treatment-on-a-complex-dynamical-system
#14
Korkut Bekiroglu, Michael A Russell, Constantino M Lagoa, Stephanie T Lanza, Megan E Piper
OBJECTIVE: To understand the dynamic relations among tobacco withdrawal symptoms to inform the development of effective smoking cessation treatments. Dynamical system models from control engineering are introduced and utilized to evaluate complex treatment effects. We demonstrate how dynamical models can be used to examine how distinct withdrawal-related processes are related over time and how treatment influences these relations. METHOD: Intensive longitudinal data from a randomized placebo-controlled smoking cessation trial (N=1504) are used to estimate a dynamical model of withdrawal-related processes including momentary craving, negative affect, quitting self-efficacy, and cessation fatigue for each of six treatment conditions (nicotine patch, nicotine lozenge, bupropion, patch + lozenge, bupropion + lozenge, and placebo)...
August 25, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28922648/a-theoretical-and-empirical-modeling-of-anxiety-integrated-with-rdoc-and-temporal-dynamics
#15
Brandon Frank, Nicholas C Jacobson, Landon Hurley, Dean McKay
The newly launched Research Domain Criteria (RDoC) emphasize specific mechanisms over diagnostic categories of psychopathology. In our view, RDoC provides a useful heuristic for mental health disorders, but does not capture the complexity of psychological data when proposed mechanisms are viewed as static entities. However, temporal and complex system dynamics may advance RDoC's utility. By investigating temporal patterns within trajectories and the interaction of complex networks, we propose that dynamic modeling provides comprehensive methods with which to investigate the etiopathology and maintenance of mental health disorders...
September 8, 2017: Journal of Anxiety Disorders
https://www.readbyqxmd.com/read/28922619/identification-of-angiogenesis-inhibitors-using-a-co-culture-cell-model-in-a-high-content-and-high-throughput-screening-platform
#16
Shuaizhang Li, Chia-Wen Hsu, Srilatha Sakamuru, Chaozhong Zou, Ruili Huang, Menghang Xia
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28922577/functional-n-formyl-peptide-receptor-2-fpr2-antagonists-based-on-ureidopropanamide-scaffold-have-potential-to-protect-against-inflammation-associated-oxidative-stress
#17
Madia Letizia Stama, Enza Lacivita, Liliya N Kirpotina, Mauro Niso, Roberto Perrone, Igor A Schepetkin, Mark T Quinn, Marcello Leopoldo
Formyl peptide receptor-2 (FPR2) is a G protein-coupled receptor belonging to the N-formyl peptide receptor (FPR) family that plays critical roles in peripheral and brain inflammatory responses. FPR2 has been proposed as a target for the development of drugs that could facilitate the resolution of chronic inflammatory reactions by enhancing endogenous anti-inflammation systems. Starting from the structure of the FPR2 agonists (R)- and (S)-4 and 2, we designed a new series of ureidopropanamide derivatives with the goal of converting functional activity from agonism to antagonism and to develop new FPR2 antagonists...
September 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28922541/effects-of-collagen-peptides-intake-on-skin-ageing-and-platelet-release-in-chronologically-aged-mice-revealed-by-cytokine-array-analysis
#18
Hongdong Song, Ling Zhang, Yongkang Luo, Siqi Zhang, Bo Li
Action mechanisms underlying various biological activities of collagen peptides (CPs) remained to be elucidated. Cytokines may play an important role in mediating these health benefits of CPs. This study aimed to systemically examine the cytokines in skin and blood regulated by CPs intake. Thirteen-month-old female Kunming mice were administered with CPs for 2 months (0 or 400 mg/kg bodyweight/day). The cytokines in skin and plasma were analysed using a 53-cytokine array and corresponding ELISA kits. In skin, CPs intake significantly down-regulated placenta growth factor (PIGF-2), insulin-like growth factor (IGF)-binding protein (IGFBP) -2 and IGFBP-3, and up-regulated platelet factor 4 (PF4), serpin E1 and transforming growth factor (TGF)-β1 ...
September 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28922520/a-review-of-joint-attention-and-social-cognitive-brain-systems-in-typical-development-and-autism-spectrum-disorder
#19
Peter Mundy
This article provides a review of the increasingly detailed literature on the neurodevelopment of joint attention. Many findings from this literature support and inform the hypothesis that the neurodevelopment of joint attention contributes to the functional development of neural systems for human social cognition. Joint attention begins to develop by 5 months of age and is tantamount to the ability to adopt a common perspective with another person. It involves a whole-brain system with nodes in the: (a) dorsal and medial frontal cortex, (b) orbital frontal/insula cortex, (c) anterior/ posterior cingulate cortex, (d) superior temporal cortex, (e) precuneus/parietal cortex, and (f) amygdala and striatum...
September 18, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28922513/purpose-processes-partnerships-and-products-4ps-to-advance-participatory-socio-environmental-modeling
#20
Steven Gray, Alexey Voinov, Michael Paolisso, Rebecca Jordan, Todd BenDor, Pierre Bommel, Pierre Glynn, Beatrice Hedelin, Klaus Hubacek, Josh Introne, Nagesh Kolagani, Bethany Laursen, Christina Prell, Laura Schmitt-Olabisi, Alison Singer, Eleanor Sterling, Moira Zellner
Including stakeholders in environmental model building and analysis is an increasingly popular approach to understanding ecological change. This is because stakeholders often hold valuable knowledge about socio-environmental dynamics and collaborative forms of modeling produce important boundary objects used to collectively reason about environmental problems. Although the number of participatory modeling (PM) case studies and the number of researchers adopting these approaches has grown in recent years, the lack of standardized reporting and limited reproducibility have prevented PM's establishment and advancement as a cohesive field of study...
September 18, 2017: Ecological Applications: a Publication of the Ecological Society of America
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