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https://www.readbyqxmd.com/read/28732272/screening-of-the-open-scaffolds-collection-from-compounds-australia-identifies-a-new-chemical-entity-with-anthelmintic-activities-against-different-developmental-stages-of-the-barber-s-pole-worm-and-other-parasitic-nematodes
#1
Sarah Preston, Yaqing Jiao, Jonathan B Baell, Jennifer Keiser, Simon Crawford, Anson V Koehler, Tao Wang, Moana M Simpson, Ray M Kaplan, Karla J Cowley, Kaylene J Simpson, Andreas Hofmann, Abdul Jabbar, Robin B Gasser
The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the 'Open Scaffolds' collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the 'Open Scaffolds' collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays...
May 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28730751/tuberculosis-and-biologics-in-rheumatology-india-a-special-situation
#2
REVIEW
Rohini Handa, Sundeep Upadhyaya, Sanjiv Kapoor, Ramesh Jois, Bimlesh D Pandey, Anuj K Bhatnagar, Ashwani Khanna, Vishal Goyal, Kamal Kumar
India has a huge patient burden of rheumatic diseases (RDs) including rheumatoid arthritis. The use of biologics has transformed the treatment paradigm for RD; however, biologic treatment-related infections (especially tuberculosis [TB]) are an area of potential concern for TB-endemic nations like India. Anti-tumor necrosis factor (TNF) therapy impairs the physiological TNF-mediated signaling and may cause reactivation and dissemination of latent TB infection (LTBI). Careful screening is, thus, crucial in RD patients who are about to commence anti-TNF treatment...
July 21, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28729851/development-and-validation-of-an-enzyme-linked-immunosorbent-assay-for-the-detection-of-binding-anti-drug-antibodies-against-interferon-beta
#3
Kathleen Ingenhoven, Daniel Kramer, Poul Erik Jensen, Christina Hermanrud, Malin Ryner, Florian Deisenhammer, Marc Pallardy, Til Menge, Hans-Peter Hartung, Bernd C Kieseier, Elisa Bertotti, Paul Creeke, Anna Fogdell-Hahn, Clemens Warnke
OBJECTIVE: To develop and validate a method for the detection of binding anti-drug antibodies (ADAs) against interferon beta (IFN-β) in human serum as part of a European initiative (ABIRISK) aimed at the prediction and analysis of clinical relevance of anti-biopharmaceutical immunization to minimize the risk. METHOD: A two-tiered bridging enzyme-linked immunosorbent assay (ELISA) format was selected and validated according to current recommendations. Screening assay: ADA in serum samples form complexes with immobilized IFN-β and biotinylated IFN-β, which are then detected using HRP labeled Streptavidin and TMB substrate...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#4
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28706384/antimicrobial-susceptibility-risk-factors-and-prevalence-of-bla-cefotaximase-temoneira-and-sulfhydryl-variable-genes-among-escherichia-coli-in-community-acquired-pediatric-urinary-tract-infection
#5
Kallyadan V Nisha, Shetty A Veena, Shenoy D Rathika, Shenoy M Vijaya, Shetty K Avinash
INTRODUCTION: The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). OBJECTIVES: The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E...
July 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28701572/clinical-application-of-targeted-deep-sequencing-in-solid-cancer-patients-utility-of-targeted-deep-sequencing-for-biomarker-selected-clinical-trial
#6
Seung Tae Kim, Kyoung-Mee Kim, Nayoung K D Kim, Joon Oh Park, Soomin Ahn, Jae-Won Yun, Kyu-Tae Kim, Se Hoon Park, Peter J Park, Hee Cheol Kim, Tae Sung Sohn, Dong Il Choi, Jong Ho Cho, Jin Seok Heo, Wooil Kwon, Hyuk Lee, Byung-Hoon Min, Sung No Hong, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Woong-Yang Park, Jeeyun Lee
Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular-screening program was intended to route participants to different candidate drugs in trials based on clinical-sequencing reports. In this screening program, we used a custom target-enrichment panel consisting of cancer-related genes to interrogate single-nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions...
July 12, 2017: Oncologist
https://www.readbyqxmd.com/read/28698171/natural-compounds-for-the-treatment-of-psoriatic-arthritis-a-proposal-based-on-multi-targeted-osteoclastic-regulation-and-on-a-preclinical-study
#7
Shiqiang Deng, Jianwen Cheng, Jinmin Zhao, Felix Yao, Jiake Xu
BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting approximately 2% to 3% of the population globally, and is characterized by both peripheral articular manifestations and axial skeletal involvement. Conventional therapies for PsA have not been fully satisfactory, though natural products (NPs) have been shown to be highly effective and represent important treatment options for psoriasis. PsA is a multigenic autoimmune disease with both environmental and genetic factors contributing to its pathogenesis...
July 11, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28685696/an-in-vivo-rat-d-glucose-stable-isotope-homeostasis-drug-discovery-screen-a-targeted-metabolomics-approach
#8
G Caldwell, Wensheng Lang
We have developed a targeted metabolomics screen which consists of using two isotopically labeled glucose compounds to conduct a dual oral glucose tolerance test in rats. This dual isotopic oral glucose tolerance test (DIS-OGTT) can be used to select drug candidates that have "on"-target or have "off"-target effects on oral glucose absorption, hepatic glucose production or glucose disposal. The DIS-OGTT assay utilized intravenously administered [6-13C1-6, 6'-2H2]-glucose and orally administered [U-13C6] glucose to monitor glucose homeostasis...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28680970/nbiochip-a-lab-on-a-chip-platform-of-mono-and-polymicrobial-biofilms-for-high-throughput-downstream-applications
#9
Anand Srinivasan, Nelson S Torres, Kai P Leung, Jose L Lopez-Ribot, Anand K Ramasubramanian
Current in vitro techniques for the culture of microorganisms, and particularly of delicate microbial biofilms, are still mostly limited to low-density plates and manual labor and are not amenable to automation and true high-throughput (HT) applications. We have developed a novel fully automated platform for the formation of mono- and polymicrobial biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans at the nanoscale level. The nBioChip is robotically printed, robustly handled, and scanned using a standard microarray reader...
May 2017: MSphere
https://www.readbyqxmd.com/read/28677274/examining-the-effect-of-social-bonds-on-the-relationship-between-adhd-and-past-arrest-in-a-representative-sample-of-adults
#10
Mark van der Maas, Nathan J Kolla, Patricia G Erickson, Christine M Wickens, Robert E Mann, Evelyn Vingilis
BACKGROUND: Several studies have found a connection between attentional deficit hyperactivity disorder (ADHD) and criminal behaviour in clinical and prison samples of adults, but there is a lack of representative general population data on this. AIM: To test relationships between histories of ADHD and arrest. Our main research question was whether any such relationship is direct or best explained by co-occurring variables, especially indicators of social bonds. METHOD: Data were from a sample of 5,376 adults (18+) representative of the general population of Ontario, Canada...
July 5, 2017: Criminal Behaviour and Mental Health: CBMH
https://www.readbyqxmd.com/read/28671522/molecular-epidemiology-of-beta-lactamase-producing-nosocomial-gram-negative-pathogens-from-north-and-south-indian-hospitals
#11
Surbhi Khurana, Purva Mathur, Arti Kapil, Chithra Valsan, Bijayini Behera
PURPOSE: Resistant Gram-negative bacterial (GNB) infections, apart from tremendously escalating the cost of treatment, are a cause for substantial morbidity and mortality among hospitalized patients. Such bacteria are rapidly acquiring resistance to many antimicrobial agents, especially the beta-lactams which are the most frequently prescribed antimicrobials in hospital and community patient care settings, and now also to colistin; a last-line drug to treat infections with such bacteria...
July 3, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28670884/low-incidence-of-the-dpd-ivs14-1g-a-polymorphism-in-jordanian-breast-and-colorectal-cancer-patients
#12
Mohammad Al-Khateeb, Abdalla Awidi, Kamal Al-Hadidi, Abdelkader Battah
Background: Dihydropyrimidine dehydrogenase (DPD) is a crucial enzyme in the catabolism of 5-fluorouracil (5-FU), a drug that is frequently used in cancer therapy. Patients with deficient DPD activity are at risk of developing severe 5-FU–associated toxicity. One possible cause of deficiency is genetic polymorphisms in the DPD gene, such as IVS14+1G>A. Aim: The present study was conducted to screen for the IVS14+1G>A polymorphism in cancer patients receiving 5-FU and a control group. Methods: A total of 40 cancer patients (30 colorectal cancer (CRC) and 10 breast cancer patients) were enrolled in this study...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28668282/brain-infusion-of-%C3%AE-synuclein-oligomers-induces-motor-and-non-motor-parkinson-s-disease-like-symptoms-in-mice
#13
Juliana T S Fortuna, Matthias Gralle, Danielle Beckman, Fernanda S Neves, Luan P Diniz, Paula S Frost, Fernanda Barros-Aragão, Luís E Santos, Rafaella A Gonçalves, Luciana Romão, Daniele C Zamberlan, Felix A A Soares, Carolina Braga, Debora Foguel, Flávia C A Gomes, Fernanda G De Felice, Sergio T Ferreira, Julia R Clarke, Cláudia P Figueiredo
Parkinson's disease (PD) is characterized by motor dysfunction, which is preceded by a number of non-motor symptoms including olfactory deficits. Aggregation of α-synuclein (α-syn) gives rise to Lewy bodies in dopaminergic neurons and is thought to play a central role in PD pathology. However, whether amyloid fibrils or soluble oligomers of α-syn are the main neurotoxic species in PD remains controversial. Here, we performed a single intracerebroventricular (i.c.v.) infusion of α-syn oligomers (α-SYOs) in mice and evaluated motor and non-motor symptoms...
June 29, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28666180/history-of-cannabis-use-is-associated-with-altered-gait
#14
Verity Pearson-Dennett, Gabrielle Todd, Robert A Wilcox, Adam P Vogel, Jason M White, Dominic Thewlis
BACKGROUND: Despite evidence that cannabinoid receptors are located in movement-related brain regions (e.g., basal ganglia, cerebral cortex, and cerebellum), and that chronic cannabis use is associated with structural and functional brain changes, little is known about the long-term effect of cannabis use on human movement. The aim of the current study was to investigate balance and walking gait in adults with a history of cannabis use. We hypothesised that cannabis use is associated with subtle changes in gait and balance that are insufficient in magnitude for detection in a clinical setting...
June 21, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28662530/dna-barcoding-for-industrial-quality-assurance
#15
Tiziana Sgamma, Claire Lockie-Williams, Marco Kreuzer, Sarah Williams, Ulrike Scheyhing, Egon Koch, Adrian Slater, Caroline Howard
DNA barcoding methods originally developed for the identification of plant specimens have been applied to the authentication of herbal drug materials for industrial quality assurance. These methods are intended to be complementary to current morphological and chemical methods of identification. The adoption of these methods by industry will be accelerated by the introduction of DNA-based identification techniques into regulatory standards and monographs. The introduction of DNA methods into the British Pharmacopoeia is described, along with a reference standard for use as a positive control for DNA extraction and polymerase chain reaction (PCR)...
June 29, 2017: Planta Medica
https://www.readbyqxmd.com/read/28662177/a-new-approach-for-the-assessment-of-the-toxicity-of-polyphenol-rich-compounds-with-the-use-of-high-content-screening-analysis
#16
Magdalena Boncler, Jacek Golanski, Magdalena Lukasiak, Malgorzata Redzynia, Jaroslaw Dastych, Cezary Watala
The toxicity of in vitro tested compounds is usually evaluated based on AC50 values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating AC50. In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay...
2017: PloS One
https://www.readbyqxmd.com/read/28649306/decreasing-prevalence-of-transmitted-drug-resistance-among-art-naive-hiv-1-infected-patients-in-iceland-1996-2012
#17
Malik Sallam, Gülşen Özkaya Şahin, Hlynur Indriðason, Joakim Esbjörnsson, Arthur Löve, Anders Widell, Magnus Gottfreðsson, Patrik Medstrand
Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches...
2017: Infection Ecology & Epidemiology
https://www.readbyqxmd.com/read/28640970/prevalence-of-new-psychoactive-substances-and-prescription-drugs-in-the-belgian-driving-under-the-influence-of-drugs-population
#18
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/28636694/placebo-response-and-practice-effects-in-schizophrenia-cognition-trials
#19
Richard S E Keefe, Vicki G Davis, Philip D Harvey, Alexandra S Atkins, George M Haig, Owen Hagino, Stephen Marder, Dana C Hilt, Daniel Umbricht
Importance: Patients' previous experience with performance-based cognitive tests in clinical trials for cognitive impairment associated with schizophrenia can create practice-related improvements. Placebo-controlled trials for cognitive impairment associated with schizophrenia are at risk for these practice effects, which can be difficult to distinguish from placebo effects. Objectives: To conduct a systematic evaluation of the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) in cognitive impairment associated with schizophrenia and to examine which demographic, clinical, and cognitive characteristics were associated with improvement in placebo conditions...
June 21, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28633752/rituximab-administration-in-a-patient-with-pemphigus-vulgaris-following-reactivation-of-occult-hepatitis-b-virus-infection
#20
Soheil Tavakolpour, Tahereh Soori, Pedram Noormohammadpour, Kamran Balighi, Hamidreza Mahmoudi, Maryam Daneshpazhooh
Immunosuppressive drugs are the milestone of treatment of autoimmune diseases, but they can lead to serious complications, including hepatitis B virus reactivation in HBV carriers as well as in patients with occult HBV infection (OBI). A 36-year-old man with OBI was diagnosed with pemphigus vulgaris. He was prescribed prednisolone and his hepatitis B surface antigen turned positive. Viral replication was successfully controlled by lamivudine and adefovir. Mycophenolate mofetil and intravenous immunoglobulin  were not effective in controlling the pemphigus vulgaris...
June 20, 2017: Dermatology Online Journal
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