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High throughout drug screening

Joseph F Levy, Marjorie A Rosenberg, Philip M Farrell
BACKGROUND: Previous estimates of the cost of care for pediatric Cystic fibrosis (CF) showed wide variation, without specific summary of pulmonary drug costs. METHODS: Enrolled CF children from the Wisconsin newborn screening trial were evaluated quarterly per protocol. Assessments systematically included all treatments, hospitalizations, and nutritional and pulmonary outcomes. Direct medical costs from hospital billing and medical records from 1989 to 2010 were used to describe costs by age-ranges and subgroups throughout follow-up...
October 14, 2016: Pediatric Pulmonology
Apurv Soni, Allison Earon, Anna Handorf, Nisha Fahey, Kandarp Talati, John Bostrom, Ki Chon, Craig Napolitano, Michael Chin, John Sullivan, Shyamsundar Raithatha, Robert Goldberg, Somashekhar Nimbalkar, Jeroan Allison, Sunil Thanvi, David McManus
BACKGROUND: Atrial fibrillation, the world's most common arrhythmia, is a leading risk factor for stroke, a disease striking nearly 1.6 million Indians annually. Early detection and management of atrial fibrillation is a promising opportunity to prevent stroke but widespread screening programs in limited resource settings using conventional methods is difficult and costly. OBJECTIVE: The objective of this study is to screen people for atrial fibrillation in rural western India using a US Food and Drug Administration-approved single-lead electrocardiography device, Alivecor...
October 13, 2016: JMIR Public Health and Surveillance
Alexander Aliper, Aleksey V Belikov, Andrew Garazha, Leslie Jellen, Artem Artemov, Maria Suntsova, Alena Ivanova, Larisa Venkova, Nicolas Borisov, Anton Buzdin, Polina Mamoshina, Evgeny Putin, Andrew G Swick, Alexey Moskalev, Alex Zhavoronkov
Populations in developed nations throughout the world are rapidly aging, and the search for geroprotectors, or anti-aging interventions, has never been more important. Yet while hundreds of geroprotectors have extended lifespan in animal models, none have yet been approved for widespread use in humans. GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition...
September 24, 2016: Aging
Santiago Ávila-Ríos, Claudia García-Morales, Margarita Matías-Florentino, Karla A Romero-Mora, Daniela Tapia-Trejo, Verónica S Quiroz-Morales, Helena Reyes-Gopar, Hezhao Ji, Paul Sandstrom, Jesús Casillas-Rodríguez, Juan Sierra-Madero, Eddie A León-Juárez, Marisol Valenzuela-Lara, Carlos Magis-Rodríguez, Patricia Uribe-Zuñiga, Gustavo Reyes-Terán
BACKGROUND: WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods. METHODS: Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey...
September 14, 2016: Lancet HIV
B T Cunningham, M Zhang, Y Zhuo, L Kwon, C Race
Photonic crystal surfaces that are designed to function as wavelength-selective optical resonators have become a widely adopted platform for label-free biosensing, and for enhancement of the output of photon-emitting tags used throughout life science research and in vitro diagnostics. While some applications, such as analysis of drug-protein interactions, require extremely high resolution and the ability to accurately correct for measurement artifacts, others require sensitivity that is high enough for detection of disease biomarkers in serum with concentrations less than 1 pg/ml...
May 15, 2016: IEEE Sensors Journal
Despina Bournele, Dimitris Beis
Cardiovascular disease (CVD) is one of the leading causes of death worldwide. The most significant risk factors associated with the development of heart diseases include genetic and environmental factors such as hypertension, high blood cholesterol levels, diabetes, smoking, and obesity. Coronary artery disease accounts for the highest percentage of CVD deaths and stroke, cardiomyopathies, congenital heart diseases, heart valve defects and arrhythmias follow. The causes, prevention, and treatment of all forms of cardiovascular disease remain active fields of biomedical research, with hundreds of scientific studies published on a weekly basis...
August 8, 2016: Heart Failure Reviews
S M Grist, S S Nasseri, T Poon, C Roskelley, K C Cheung
Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 μm depth, which is insufficient to image hypoxic spheroid cores...
July 2016: Biomicrofluidics
Archana Shubhakar, Radoslaw P Kozak, Karli R Reiding, Louise Royle, Daniel I R Spencer, Daryl L Fernandes, Manfred Wuhrer
Monitoring glycoprotein therapeutics for changes in glycosylation throughout the drug's life cycle is vital, as glycans significantly modulate the stability, biological activity, serum half-life, safety, and immunogenicity. Biopharma companies are increasingly adopting Quality by Design (QbD) frameworks for measuring, optimizing, and controlling drug glycosylation. Permethylation of glycans prior to analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is a valuable tool for glycan characterization and for screening of large numbers of samples in QbD drug realization...
September 6, 2016: Analytical Chemistry
Christopher M Coleman, Jeanne M Sisk, Rebecca M Mingo, Elizabeth A Nelson, Judith M White, Matthew B Frieman
UNLABELLED: The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane...
October 1, 2016: Journal of Virology
Jimena G Dancy, Aniket S Wadajkar, Craig S Schneider, Joseph R H Mauban, Olga G Goloubeva, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim
Therapeutic nanoparticles (NPs) approved for clinical use in solid tumor therapy provide only modest improvements in patient survival, in part due to physiological barriers that limit delivery of the particles throughout the entire tumor. Here, we explore the thresholds for NP size and surface poly(ethylene glycol) (PEG) density for penetration within tumor tissue extracellular matrix (ECM). We found that NPs as large as 62nm, but less than 110nm in diameter, diffused rapidly within a tumor ECM preparation (Matrigel) and breast tumor xenograft slices ex vivo...
September 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Daniela Remane, Dirk K Wissenbach, Frank T Peters
Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) is a well-established and widely used technique in clinical and forensic toxicology as well as doping control especially for quantitative analysis. In recent years, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in biological matrices have been developed. Such methods have proven particularly useful for analysis of so-called new psychoactive substances that have appeared on recreational drug markets throughout the world...
September 2016: Clinical Biochemistry
Vanessa Cordeiro Dias, Claudio Galuppo Diniz, Ana Claudia De Oliveira Peter, Andre Netto Bastos, Victor Quinnet de Andrade Bastos, Lucas Quinnet de Andrade Bastos, Vania Lucia Da Silva
INTRODUCTION: Non-fermenting Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii are widespread in the environment and are increasingly associated with nosocomial infections. Extensive and indiscriminate use of antibiotics in hospitals has contributed to an increased number of infections caused by these microorganisms, that are resistant to a wide variety of antimicrobials, including β-lactams. This study aimed to isolate and identify carbapenem-resistant Acinetobacter spp...
2016: Journal of Infection in Developing Countries
Jun Zhang, Xin Liu, Xian-Bin Xie, Xian-Chao Cheng, Run-Ling Wang
Type 2 diabetes took insulin resistance as the main clinical manifestation. PPARs have been reported to be the therapeutic targets of metabolic disorders, such as obesity, hypertension, diabetes and cardiovascular disease. Previously, PPARγ agonist rosiglitazone was restricted in clinic due to cardiomyocytes infarction, weight gain and other serious side effects, which were mainly due to the single and selective PPARγ agonism. In recent years, multi-target directed PPARs agonists with synergistic reaction as well as fewer side-effect have been the hot topic in designing promising agents...
June 18, 2016: Chemical Biology & Drug Design
Lei Tian, Xuhui Zhu, Zhongju Chen, Weiyong Liu, Song Li, Weiting Yu, Wenqian Zhang, Xu Xiang, Ziyong Sun
BACKGROUND: Acute diarrhea is a leading cause of morbidity and mortality in children, particularly in those under the age of 5 years. Rotavirus is recognized as the leading cause of acute diarrhea in children, however, the contribution of bacterial pathogens as causative agents varies throughout the world. Here we report a hospital-based prospective study to analyze the characteristics of bacterial pathogens associated with acute diarrhea in children under 5 years of age. METHODS: Stool samples were collected from 508 patients with acute diarrhea under 5 years of age who presented at our hospital...
2016: BMC Infectious Diseases
Gabriel J Culbert, Veena Pillai, Joseph Bick, Haider A Al-Darraji, Jeffrey A Wickersham, Martin P Wegman, Alexander R Bazazi, Enrico Ferro, Michael Copenhaver, Adeeba Kamarulzaman, Frederick L Altice
Throughout Southeast Asia, repressive drug laws have resulted in high rates of imprisonment in people who inject drugs (PWID) and people living with HIV (PLH), greatly magnifying the harm associated with HIV, tuberculosis, and addiction. We review findings from Malaysia's largest prison to describe the negative synergistic effects of HIV, tuberculosis, addiction, and incarceration that contribute to a 'perfect storm' of events challenging public and personal health and offer insights into innovative strategies to control these converging epidemics...
September 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Monique J Windley, Stefan A Mann, Jamie I Vandenberg, Adam P Hill
Drug block of voltage-gated potassium channel subtype 11.1 human ether-a-go-go related gene (Kv11.1) (hERG) channels, encoded by the KCNH2 gene, is associated with reduced repolarization of the cardiac action potential and is the predominant cause of acquired long QT syndrome that can lead to fatal cardiac arrhythmias. Current safety guidelines require that potency of KV11.1 block is assessed in the preclinical phase of drug development. However, not all drugs that block KV11.1 are proarrhythmic, meaning that screening on the basis of equilibrium measures of block can result in high attrition of potentially low-risk drugs...
July 2016: Molecular Pharmacology
A V Lebedev, M Kaelen, M Lövdén, J Nilsson, A Feilding, D J Nutt, R L Carhart-Harris
Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I...
September 2016: Human Brain Mapping
Daniela Ferreira, Ana M L Seca, Diana C G A, Artur M S Silva
UNLABELLED: Human bacterial infections are still a major public health problem throughout the world. Therefore it is fundamental to understand how pathogenic bacteria interact with their human host and to develop more advanced drugs or vaccines in response to the increasing bacterial resistance. Since iron is essential to bacterial survival and growth inside the host tissues, these microorganisms have developed highly efficient iron-acquisition systems; the most common one involves the secretion of iron chelators into the extracellular environment, known as siderophores, and the corresponding siderophore-membrane receptors or transporters responsible for the iron uptake...
August 11, 2016: Journal of Proteomics
Changhe Wang, Cynthia X Shi, Keming Rou, Yan Zhao, Xiaobin Cao, Wei Luo, Enwu Liu, Zunyou Wu
BACKGROUND: Hepatitis C virus (HCV) is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT) program. METHODS: Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution...
2016: PloS One
Patrick A Smith
BACKGROUND: Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded. PURPOSE: To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA)...
April 2016: American Journal of Sports Medicine
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