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Critical labs

Christopher Goldring, Daniel J Antoine, Frank Bonner, Jonathan Crozier, Chris Denning, Robert J Fontana, Neil A Hanley, David C Hay, Magnus Ingelman-Sundberg, Satu Juhila, Neil Kitteringham, Beatriz Silva-Lima, Alan Norris, Chris Pridgeon, James A Ross, Rowena Sison Young, Danilo Tagle, Belen Tornesi, Bob van de Water, Richard J Weaver, Fang Zhang, B Kevin Park
Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalised toxicology to determine inter-individual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury (DILI) means that no current single cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human DILI...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Saad Mohammed Dahlawi, Samreen Siddiqui
Easy availability, preparation technique, and economic value make calcium polysulphide (CaS x ) a very useful inorganic chemical for various field and industrial applications. In this article, disparate applications of CaS x solution have been reviewed to suggest potential and future consolidation. This article also encompasses the physiochemical properties and production of CaS x solution, with critical appraisal on research focusing on CaS x application in agriculture industries and removal of potentially toxic elements (PTEs) from the environment...
October 19, 2016: Environmental Science and Pollution Research International
C Aeberhard, C Steuer, C Saxer, A Huber, Z Stanga, S Mühlebach
BACKGROUND: Parenteral antiepileptic drugs are frequently used in critically ill patients for seizure control therapy or prevention. Many of these patients require additional parenteral nutrition (PN). Therefore, a parallel infusion of the frequently used antiepileptic drug levetiracetam (LEV) is interesting in terms of the restricted i.v. lines (e.g., neonates). The potential interactions of the complex PN admixture with the drug product and the appropriate admixing of a drug at effective dosages require physicochemical lab assessments to obtain specific and reliable pharmaceutical documentation for the intended admixing...
October 11, 2016: European Journal of Pharmaceutical Sciences
Trevor A Graham, Andrea Sottoriva
The temporal dynamics of cancer evolution remain elusive because it is impractical to longitudinally observe cancers unperturbed by treatment. Consequently, our knowledge of how cancers grow largely derives from inferences made from a single point in time - the end point in the cancer's evolution when it is removed from the body and studied in the lab. Fortuitously however, the cancer genome, by virtue of on-going mutations that uniquely mark clonal lineages within the tumour, provides a rich yet surreptitious record of cancer development...
October 14, 2016: Journal of Pathology
Mara C Modest, Eric J Moore, Kathryn M Van Abel, Jeffrey R Janus, John R Sims, Daniel L Price, Kerry D Olsen
OBJECTIVES/HYPOTHESIS: Discuss current techniques utilizing the scapular tip and subscapular system for free tissue reconstruction of maxillary defects and highlight the impact of medical modeling on these techniques with a case series. STUDY DESIGN: Case review series at an academic hospital of patients undergoing maxillectomy + thoracodorsal scapula composite free flap (TSCF) reconstruction. Three-dimensional (3D) models were used in the last five cases. METHODS: 3D modeling, surgical, functional, and aesthetic outcomes were reviewed...
October 12, 2016: Laryngoscope
Tarig Elraiyah, Calvin R Jerde, Shikshya Shrestha, Rentian Wu, Qian Nie, Nasra H Giama, Vivekananda Sarangi, Lewis R Roberts, Steven M Offer, Robert B Diasio
Clinical studies have identified specific genetic variants in dihydropyrimidine dehydrogenase (DPD, DPYD gene) as predictors of severe adverse toxicity to the commonly used chemotherapeutic 5-fluorouracil; however, these studies have focused on European and European-American populations. Our lab recently demonstrated that additional variants in non-European haplotypes are predictive of 5-FU toxicity. The objective of this study was to identify potential risk variants in an under-studied East African population relevant to our institution's catchment area...
October 11, 2016: Clinical Pharmacology and Therapeutics
Citsabehsan Devendran, Thomas Albrecht, Jason Brenker, Tuncay Alan, Adrian Neild
The use of ultrasonic fields to manipulate particles, cells and droplets has become widespread in lab on a chip (LOC) systems. There are two dominant actuation methods, the use of bulk acoustic waves (BAW) or surface acoustic waves (SAW). The development of BAW actuated systems have been underpinned by a robust understanding of the link between the ultrasonic field and forces which can be generated. In this work, we examine this link for standing surface acoustic waves (SSAW) comparing the relative strengths of streaming induced drag and acoustic radiation forces on suspended particles...
September 21, 2016: Lab on a Chip
Isabelle Meyts, Barbara Bosch, Alexandre Bolze, Bertrand Boisson, Yuval Itan, Aziz Belkadi, Vincent Pedergnana, Leen Moens, Capucine Picard, Aurélie Cobat, Xavier Bossuyt, Laurent Abel, Jean-Laurent Casanova
The advent of next-generation sequencing (NGS) in 2010 has transformed medicine, particularly the growing field of inborn errors of immunity. NGS has facilitated the discovery of novel disease-causing genes and the genetic diagnosis of patients with monogenic inborn errors of immunity. Whole-exome sequencing (WES) is presently the most cost-effective approach for research and diagnostics, although whole-genome sequencing offers several advantages. The scientific or diagnostic challenge consists in selecting 1 or 2 candidate variants among thousands of NGS calls...
October 2016: Journal of Allergy and Clinical Immunology
Youtao Liu, Jesus Lacal, Richard A Firtel, Arjan Kortholt
The directional movement towards extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in the activated downstream signaling pathways. Studies with mainly Dictyostelium and mammalian neutrophils as experimental systems have shown that chemotaxis is mediated by a complex network of signaling pathways...
October 7, 2016: Small GTPases
Pauline Valois, Emilie Verneuil, Francois Lequeux, Laurence Talini
When a dry soluble polymer is put in contact with a large quantity of solvent, it swells and forms a transient gel, and eventually, yields a dilute solution of polymers. Everyday lab experience shows that when the molar mass is large, namely tens of times larger than entanglement mass, this dissolution process is slow and difficult and may require stirring. Here, in agreement with previous results, we found that the time needed to turn a dry grain into a dilute solution is not limited by water diffusion in the glassy or semi-crystalline dry polymer, but rather by the life-time of the transient gel made of entangled chains...
October 4, 2016: Soft Matter
Qi Zheng, Elizabeth A Grice
Accurate mapping of next-generation sequencing (NGS) reads to reference genomes is crucial for almost all NGS applications and downstream analyses. Various repetitive elements in human and other higher eukaryotic genomes contribute in large part to ambiguously (non-uniquely) mapped reads. Most available NGS aligners attempt to address this by either removing all non-uniquely mapping reads, or reporting one random or "best" hit based on simple heuristics. Accurate estimation of the mapping quality of NGS reads is therefore critical albeit completely lacking at present...
October 2016: PLoS Computational Biology
Kar M Ang, Leslie Y Yeo, Yew M Hung, Ming K Tan
The ability to drive microcentrifugation for efficient micromixing and particle concentration and separation on a microfluidic platform is critical for a wide range of lab-on-a-chip applications. In this work, we investigate the use of amplitude modulation to enhance the efficiency of the microcentrifugal recirculation flows in surface acoustic wave microfluidic systems, thus concomitantly reducing the power consumption in these devices for a given performance requirement-a crucial step in the development of miniaturized, integrated circuits for true portable functionality...
September 2016: Biomicrofluidics
Michael G Tassia, Johanna T Cannon, Charlotte E Konikoff, Noa Shenkar, Kenneth M Halanych, Billie J Swalla
Phylum Hemichordata, composed of worm-like Enteropneusta and colonial Pterobranchia, has been reported to only contain about 100 species. However, recent studies of hemichordate phylogeny and taxonomy suggest the species number has been largely underestimated. One issue is that species must be described by experts, and historically few taxonomists have studied this group of marine invertebrates. Despite this previous lack of coverage, interest in hemichordates has piqued in the past couple of decades, as they are critical to understanding the evolution of chordates-as acorn worms likely resemble the deuterostome ancestor more closely than any other extant animal...
2016: PloS One
Dinesh Kumar, Sandeep R Vemula, Narayanaganesh Balasubramanian, Gregory R Cook
Stereoselective indium-mediated organic reactions have enjoyed tremendous growth in the last 25 years. This is in part due to the insensitivity of allylindium to moisture, affording facile and practical reaction conditions coupled with outstanding functional group tolerance and minimal side reactions. Despite the plethora of articles about allylindium, there is much yet to be discovered and exploited for efficient and sustainable synthesis. In this Account, we describe indium-mediated synthetic methods for the preparation of chiral amines with the aim to present a balance of practical method development, novel asymmetric chemistry, and mechanistic understanding that impact multiple chemical and materials science disciplines...
October 4, 2016: Accounts of Chemical Research
Diego Lops, Edoardo Stellini, Luca Sbricoli, Niccolò Cea, Eugenio Romeo, Eriberto Bressan
PURPOSE: The aim of the present clinical trial was to analyze, through spectrophotometric digital technology, the influence of the abutment material on the color of the peri-implant soft tissue in patients with thin gingival biotype. MATERIAL AND METHODS: Thirty-seven patients received an endosseous dental implant in the anterior maxilla. At time of each definitive prosthesis delivery, an all-ceramic crown has been tried on gold, titanium and zirconia abutment. Peri-implant soft-tissue color has been measured through a spectrophotometer after the insertion of each single abutment...
October 3, 2016: Clinical Oral Implants Research
Rebecca B Price, Meredith Wallace, Jennie M Kuckertz, Nader Amir, Simona Graur, Logan Cummings, Paul Popa, Per Carlbring, Yair Bar-Haim
Computer-based approaches, such as Attention Bias Modification (ABM), could help improve access to care for anxiety. Study-level meta-analyses of ABM have produced conflicting findings and leave critical questions unresolved regarding ABM's mechanisms of action and clinical potential. We pooled patient-level datasets from randomized controlled trials of children and adults with high-anxiety. Attentional bias (AB) towards threat, the target mechanism of ABM, was tested as an outcome and a mechanistic mediator and moderator of anxiety reduction...
September 20, 2016: Clinical Psychology Review
Michael J Bernstein, Kiera Reifschneider, Ira Bennett, Jameson M Wetmore
Helping scientists and engineers challenge received assumptions about how science, engineering, and society relate is a critical cornerstone for macroethics education. Scientific and engineering research are frequently framed as first steps of a value-free linear model that inexorably leads to societal benefit. Social studies of science and assessments of scientific and engineering research speak to the need for a more critical approach to the noble intentions underlying these assumptions. "Science Outside the Lab" is a program designed to help early-career scientists and engineers understand the complexities of science and engineering policy...
September 28, 2016: Science and Engineering Ethics
Keita Nishiyama, Makoto Sugiyama, Takao Mukai
Lactic acid bacteria (LAB) are Gram-positive bacteria that are natural inhabitants of the gastrointestinal (GI) tracts of mammals, including humans. Since Mechnikov first proposed that yogurt could prevent intestinal putrefaction and aging, the beneficial effects of LAB have been widely demonstrated. The region between the duodenum and the terminal of the ileum is the primary region colonized by LAB, particularly the Lactobacillus species, and this region is covered by a mucus layer composed mainly of mucin-type glycoproteins...
September 20, 2016: Microorganisms
Timothy J Morris, Andrew Picken, Duncan M C Sharp, Nigel K H Slater, Christopher J Hewitt, Karen Coopman
With the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me2SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 °C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration...
September 20, 2016: Cryobiology
Maxim V Gerashchenko, Vadim N Gladyshev
Ribosome profiling has emerged as a powerful method to assess global gene translation, but methodological and analytical challenges often lead to inconsistencies across labs and model organisms. A critical issue in ribosome profiling is nuclease treatment of ribosome-mRNA complexes, as it is important to ensure both stability of ribosomal particles and complete conversion of polysomes to monosomes. We performed comparative ribosome profiling in yeast and mice with various ribonucleases including I, A, S7 and T1, characterized their cutting preferences, trinucleotide periodicity patterns and coverage similarities across coding sequences, and showed that they yield comparable estimations of gene expression when ribosome integrity is not compromised...
September 15, 2016: Nucleic Acids Research
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