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Find video protocols related to scientific articles indexed in Pubmed.
Discovery of Desketoraloxifene Analogues as Inhibitors of Mammalian, Pseudomonas aeruginosa, and NAPE Phospholipase D Enzymes.
ACS Chem. Biol.
PUBLISHED: 11-11-2014
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Phospholipase D (PLD) hydrolyses cellular lipids to produce the important lipid second messenger phosphatidic acid. A PLD enzyme expressed by Pseudomonas aeruginosa (PldA) has been shown to be important in bacterial infection, and NAPE-PLD has emerged as being key in the synthesis of endocannabinoids. In order to better understand the biology and therapeutic potential of these less explored PLD enzymes, small molecule tools are required. Selective estrogen receptor modulators (SERMs) have been previously shown to inhibit mammalian PLD (PLD1 and PLD2). By targeted screening of a library of SERM analogues, additional parallel synthesis, and evaluation in multiple PLD assays, we discovered a novel desketoraloxifene-based scaffold that inhibited not only the two mammalian PLDs but also structurally divergent PldA and NAPE-PLD. This finding represents an important first step toward the development of small molecules possessing universal inhibition of divergent PLD enzymes to advance the field.
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Canadian demand for highly qualified personnel for therapeutic evaluation: an opportunity for academic institutions.
J Popul Ther Clin Pharmacol
PUBLISHED: 10-19-2014
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Achievement of optimal therapeutics requires individuals with analytic skills appropriate to the balancing of enterprise, innovation and the need for rigorous scientific validation. A synergistic convergence of discovery research, clinical investigation, evaluative, regulatory and implementation sciences will be essential. None of the needed research capacities are likely to prove obtainable on demand. On the contrary, they require accurate projection of future needs and careful planning of post-secondary training programs. A survey conducted for Health Canada in 2010 revealed significant shortfalls in research skills available outside government and industry. This commentary argues that such an environment represents an outstanding opportunity for the academic community to demonstrate that it is eager to meet the needs of the Canadian public. University leaders should be assertive about their commitment to the ideals of patient oriented research and all governments should be clear about deliverables anticipated in return for consistent post-secondary funding.  
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Post-market drug evaluation research training capacity in Canada: an environmental scan of canadian educational institutions.
J Popul Ther Clin Pharmacol
PUBLISHED: 10-19-2014
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Background Ongoing efforts by Health Canada intended to modernize the legislation and regulation of pharmaceuticals will help improve the safety and effectiveness of drug products. It will be imperative to ensure that comprehensive and specialized training sites are available to train researchers to support the regulation of therapeutic products.  ObjectivesThe objective of this educational institution inventory was to conduct an environmental scan of educational institutions in Canada able to train students in areas of post-market drug evaluation research. MethodsA systematic web-based environmental scan of Canadian institutions was conducted. The website of each university was examined for potential academic programs.  Six core programmatic areas were determined a priori as necessary to train competent post-market drug evaluation researchers. These included biostatistics, epidemiology, pharmacoepidemiology, health economics or pharmacoeconomics, pharmacogenetics or pharmacogenomics and patient safety/pharmacovigilance. Results Twenty-three academic institutions were identified that had the potential to train students in post-market drug evaluation research. Overall, 23 institutions taught courses in epidemiology, 22 in biostatistics, 17 in health economics/pharmacoeconomics, 5 in pharmacoepidemiology, 5 in pharmacogenetics/pharmacogenomics, and 3 in patient safety/pharmacovigilance. Of the 23 institutions, only the University of Ottawa offered six core courses. Two institutions offered five, seven offered four and the remaining 14 offered three or fewer. It is clear that some institutions may offer programs not entirely reflected in the nomenclature used for this review. Conclusions As Heath Canada moves towards a more progressive licensing framework, augmented training to increase research capacity and expertise in drug safety and effectiveness is timely and necessary.   
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Long-Range C-H Bond Activation by Rh(III)-Carboxylates.
J. Am. Chem. Soc.
PUBLISHED: 10-10-2014
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Traditional C-H bond activation by a concerted metalation-deprotonation (CMD) mechanism involves precoordination of the C-H bond followed by deprotonation from an internal base. Reported herein is a "through-arene" activation of an uncoordinated benzylic C-H bond that is 6 bonds away from a Rh(III) ion. The mechanism, which was investigated by experimental and DFT studies, proceeds through a dearomatized xylene intermediate. This intermediate was observed spectroscopically upon addition of a pyridine base to provide a thermodynamic trap.
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Acculturation and the prevalence of diabetes in US Latino Adults, National Health and Nutrition Examination Survey 2007-2010.
Prev Chronic Dis
PUBLISHED: 10-10-2014
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US Latinos are growing at the fastest rate of any racial/ethnic group in the United States and have the highest lifetime risk of diabetes. Acculturation may increase the risk of diabetes among all Latinos, but this hypothesis has not been studied in a nationally representative sample. The objective of this study was to test the hypothesis that acculturation was associated with an increased risk of diabetes in such a sample.
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Exploring a 2-Naphthoic Acid Template for the Structure-Based Design of P2Y14 Receptor Antagonist Molecular Probes.
ACS Chem. Biol.
PUBLISHED: 10-10-2014
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The P2Y14 receptor (P2Y14R), one of eight P2Y G protein-coupled receptors (GPCR), is involved in inflammatory, endocrine, and hypoxic processes and is an attractive pharmaceutical target. The goal of this research is to develop high-affinity P2Y14R fluorescent probes based on the potent and highly selective antagonist 4-(4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl)-2-naphthoic acid (6, PPTN). A model of hP2Y14R based on recent hP2Y12R X-ray structures together with simulated antagonist docking suggested that the piperidine ring is suitable for fluorophore conjugation while preserving affinity. Chain-elongated alkynyl or amino derivatives of 6 for click or amide coupling were synthesized, and their antagonist activities were measured in hP2Y14R-expressing CHO cells. Moreover, a new Alexa Fluor 488 (AF488) containing derivative 30 (MRS4174, Ki = 80 pM) exhibited exceptionally high affinity, as compared to 13 nM for the alkyne precursor 22. A flow cytometry assay employing 30 as a fluorescent probe was used to quantify specific binding to P2Y14R. Known P2Y receptor ligands inhibited binding of 30 with properties consistent with their previously established receptor selectivities and affinities. These results illustrate that potency in this series of 2-naphthoic acid derivatives can be preserved by chain functionalization, leading to highly potent fluorescent molecular probes for P2Y14R. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. This approach demonstrates the predictive power of GPCR homology modeling and the relevance of newly determined X-ray structures to GPCR medicinal chemistry.
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A pilot randomized control trial: testing a transitional care model for acute psychiatric conditions.
J Am Psychiatr Nurses Assoc
PUBLISHED: 10-08-2014
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People with multiple and persistent mental and physical health problems have high rates of transition failures when transferring from a hospital level of care to home. The transitional care model (TCM) is evidence-based and demonstrated to improve posthospital outcomes for elderly with physical health conditions, but it has not been studied in the population with serious mental illness.
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Tricuspid Annular Plane Systolic Excursion Is Reduced in Infants with Pulmonary Hypertension.
Echocardiography
PUBLISHED: 10-08-2014
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Right ventricular (RV) function is reduced in infants with pulmonary hypertension (PH) but echocardiographic assessment can be challenging. We sought to determine the role of tricuspid annular plane systolic excursion (TAPSE) in infants with PH and compared it with other markers such as tricuspid annular S' and RV fractional area change (RVFAC).
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Age-Related Normative Changes in Phasic Orthostatic Blood Pressure in a Large Population Study: Findings From The Irish Longitudinal Study on Ageing (TILDA).
Circulation
PUBLISHED: 10-02-2014
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In this report, we provide the first normative reference data and prevalence estimates of impaired orthostatic blood pressure (BP) stabilization, initial orthostatic hypotension, and orthostatic hypotension based on beat-to-beat blood pressure methods in a population-representative sample.
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A new active cavitation mapping technique for pulsed HIFU applications--bubble Doppler.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 09-30-2014
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In this work, a new active cavitation mapping technique for pulsed high-intensity focused ultrasound (pHIFU) applications termed bubble Doppler is proposed and its feasibility is tested in tissue-mimicking gel phantoms. pHIFU therapy uses short pulses, delivered at low pulse repetition frequency, to cause transient bubble activity that has been shown to enhance drug and gene delivery to tissues. The current gold standard for detecting and monitoring cavitation activity during pHIFU treatments is passive cavitation detection (PCD), which provides minimal information on the spatial distribution of the bubbles. B-mode imaging can detect hyperecho formation, but has very limited sensitivity, especially to small, transient microbubbles. The bubble Doppler method proposed here is based on a fusion of the adaptations of three Doppler techniques that had been previously developed for imaging of ultrasound contrast agents-color Doppler, pulse-inversion Doppler, and decorrelation Doppler. Doppler ensemble pulses were interleaved with therapeutic pHIFU pulses using three different pulse sequences and standard Doppler processing was applied to the received echoes. The information yielded by each of the techniques on the distribution and characteristics of pHIFU-induced cavitation bubbles was evaluated separately, and found to be complementary. The unified approach-bubble Doppler-was then proposed to both spatially map the presence of transient bubbles and to estimate their sizes and the degree of nonlinearity.
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Membrane-induced Allosteric Control of Phospholipase C-? Isozymes.
J. Biol. Chem.
PUBLISHED: 09-05-2014
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All peripheral membrane proteins must negotiate unique constraints intrinsic to the biological interface of lipid bilayers and the cytosol. Phospholipase C-? (PLC-?) isozymes hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. PLC-? isozymes are autoinhibited, and several proteins, including G?q, G??, and Rac1, directly engage distinct regions of these phospholipases to release autoinhibition. To understand this process, we used a novel, soluble analog of PIP2 that increases in fluorescence upon cleavage to monitor phospholipase activity in real time in the absence of membranes or detergents. High concentrations of G?q or G?1?2 did not activate purified PLC-?3 under these conditions despite their robust capacity to activate PLC-?3 at membranes. In addition, mutants of PLC-?3 with crippled autoinhibition dramatically accelerated the hydrolysis of PIP2 in membranes without an equivalent acceleration in the hydrolysis of the soluble analog. Our results illustrate that membranes are integral for the activation of PLC-? isozymes by diverse modulators, and we propose a model describing membrane-mediated allosterism within PLC-? isozymes.
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Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.
Addict Biol
PUBLISHED: 08-19-2014
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Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and ?-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.
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Simultaneous In Situ Quantification of Two Cellular Lipid Pools Using Orthogonal Fluorescent Sensors.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-11-2014
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Lipids regulate a wide range of biological activities. Since their local concentrations are tightly controlled in a spatiotemporally specific manner, the simultaneous quantification of multiple lipids is essential for elucidation of the complex mechanisms of biological regulation. Here, we report a new method for the simultaneous in situ quantification of two lipid pools in mammalian cells using orthogonal fluorescent sensors. The sensors were prepared by incorporating two environmentally sensitive fluorophores with minimal spectral overlap separately into engineered lipid-binding proteins. Dual ratiometric analysis of imaging data allowed accurate, spatiotemporally resolved quantification of two different lipids on the same leaflet of the plasma membrane or a single lipid on two opposite leaflets of the plasma membrane of live mammalian cells. This new imaging technology should serve as a powerful tool for systems-level investigation of lipid-mediated cell signaling and regulation.
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Discovery of a Highly Selective PLD2 Inhibitor (ML395): A New Probe with Improved Physiochemical Properties and Broad-Spectrum Antiviral Activity against Influenza Strains.
ChemMedChem
PUBLISHED: 08-04-2014
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Further chemical optimization of the halopemide-derived family of dual phospholipase?D1/2 (PLD1/2) inhibitors afforded ML395 (VU0468809), a potent, >80-fold PLD2 selective allosteric inhibitor (cellular PLD1, IC50 >30?000?nM; cellular PLD2, IC50 =360?nM). Moreover, ML395 possesses an attractive in vitro DMPK profile, improved physiochemical properties, ancillary pharmacology (Eurofins Panel) cleaner than any other reported PLD inhibitor, and has been found to possess interesting activity as an antiviral agent in cellular assays against a range of influenza strains (H1, H3, H5 and H7).
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Ventricular assist devices in children.
Curr. Opin. Cardiol.
PUBLISHED: 08-02-2014
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Ventricular assist devices (VADs) have revolutionized heart failure management in adults. Recently, VADs have similarly taken a prominent role in the management of end-stage heart failure in children. The purpose of this review is to describe the indications for VADs in children, types of devices available, current outcomes, and future directions of VAD therapy.
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Characteristics and thirty-day outcomes of emergency department patients with elevated creatine kinase.
Acad Emerg Med
PUBLISHED: 07-22-2014
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Rhabdomyolysis, as defined by an elevation in creatine kinase (CK), may lead to hemodialysis and death in emergency department (ED) patients, but the patient characteristics, associated conditions, and 30-day outcomes of patients with CK values over 1,000 U/L have not been described.
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Center of mass mechanics of chimpanzee bipedal walking.
Am. J. Phys. Anthropol.
PUBLISHED: 07-16-2014
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Center of mass (CoM) oscillations were documented for 81 bipedal walking strides of three chimpanzees. Full-stride ground reaction forces were recorded as well as kinematic data to synchronize force to gait events and to determine speed. Despite being a bent-hip, bent-knee (BHBK) gait, chimpanzee walking uses pendulum-like motion with vertical oscillations of the CoM that are similar in pattern and relative magnitude to those of humans. Maximum height is achieved during single support and minimum height during double support. The mediolateral oscillations of the CoM are more pronounced relative to stature than in human walking when compared at the same Froude speed. Despite the pendular nature of chimpanzee bipedalism, energy recoveries from exchanges of kinetic and potential energies are low on average and highly variable. This variability is probably related to the poor phasic coordination of energy fluctuations in these facultatively bipedal animals. The work on the CoM per unit mass and distance (mechanical cost of transport) is higher than that in humans, but lower than that in bipedally walking monkeys and gibbons. The pronounced side sway is not passive, but constitutes 10% of the total work of lifting and accelerating the CoM. CoM oscillations of bipedally walking chimpanzees are distinctly different from those of BHBK gait of humans with a flat trajectory, but this is often described as "chimpanzee-like" walking. Human BHBK gait is a poor model for chimpanzee bipedal walking and offers limited insights for reconstructing early hominin gait evolution. Am J Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.
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Trianionic pincer and pincer-type metal complexes and catalysts.
Chem Soc Rev
PUBLISHED: 06-14-2014
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Trianionic pincer and pincer-type ligands are the focus of this review. Metal ions from across the periodic table, from main group elements, transition metals, and the rare earths, are combined with trianionic pincer ligands to produce some of the most interesting complexes to appear in the literature over the past decade. This review provides a comprehensive examination of the synthesis, characterization, properties, and catalytic applications of trianionic pincer metal complexes. Some of the interesting applications employing trianionic pincer and pincer-type complexes include: (1) catalyzed aerobic oxidation, (2) alkene isomerization, (3) alkene and alkyne polymerization, (4) nitrene and carbene group transfer, (5) fundamental transformations such as oxygen-atom transfer, (6) nitrogen-atom transfer, (7) O2 activation, (8) C-H bond activation, (9) disulfide reduction, and (10) ligand centered storage of redox equivalents (i.e. redox active ligands). Expansion of the architecture, type of donor atoms, chelate ring size, and steric and electronic properties of trianionic pincer ligands has occurred rapidly over the past ten years. This review is structured according to the type of pincer donor atoms that bind to the metal ion. The type of donor atoms within trianionic pincer and pincer-type ligands to be discussed include: NCN(3-), OCO(3-), CCC(3-), redox active NNN(3-), NNN(3-), redox active ONO(3-), ONO(3-), and SNS(3-). Since this is the first review of trianionic pincer and pincer-type ligands, an emphasis is placed on providing the reader with in-depth discussion of synthetic methods, characterization data, and highlights of these complexes as catalysts.
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Opioid attentional bias and cue-elicited craving predict future risk of prescription opioid misuse among chronic pain patients.
Drug Alcohol Depend
PUBLISHED: 06-13-2014
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Some chronic pain patients receiving long-term opioid analgesic pharmacotherapy are at risk for misusing opioids. Like other addictive behaviors, risk of opioid misuse may be signaled by an attentional bias (AB) towards drug-related cues. The purpose of this study was to examine opioid AB as a potential predictor of opioid misuse among chronic pain patients following behavioral treatment.
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Radial basis functions for combining shape and speckle tracking in 4D echocardiography.
IEEE Trans Med Imaging
PUBLISHED: 06-04-2014
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Quantitative analysis of left ventricular deformation can provide valuable information about the extent of disease as well as the efficacy of treatment. In this work, we develop an adaptive multi-level compactly supported radial basis approach for deformation analysis in 3D+time echocardiography. Our method combines displacement information from shape tracking of myocardial boundaries (derived from B-mode data) with mid-wall displacements from radio-frequency-based ultrasound speckle tracking. We evaluate our methods on open-chest canines (N=8) and show that our combined approach is better correlated to magnetic resonance tagging-derived strains than either individual method. We also are able to identify regions of myocardial infarction (confirmed by postmortem analysis) using radial strain values obtained with our approach.
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Neurophysiological evidence for remediation of reward processing deficits in chronic pain and opioid misuse following treatment with Mindfulness-Oriented Recovery Enhancement: exploratory ERP findings from a pilot RCT.
J Behav Med
PUBLISHED: 06-03-2014
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Dysregulated processing of natural rewards may be a central pathogenic process in the etiology and maintenance of prescription opioid misuse and addiction among chronic pain patients. This study examined whether a Mindfulness-Oriented Recovery Enhancement (MORE) intervention could augment natural reward processing through training in savoring as indicated by event-related brain potentials (ERPs). Participants were chronic pain patients at risk for opioid misuse who were randomized to 8 weeks of MORE (n = 11) or a support group control condition (n = 18). ERPs to images representing naturally rewarding stimuli (e.g., beautiful landscapes, intimate couples) and neutral images were measured before and after 8 weeks of treatment. Analyses focused on the late positive potential (LPP)-an ERP response in the 400-1,000 ms time window thought to index allocation of attention to emotional information. Treatment with MORE was associated with significant increases in LPP response to natural reward stimuli relative to neutral stimuli which were correlated with enhanced positive affective cue-responses and reductions in opioid craving from pre- to post-treatment. Findings suggest that cognitive training regimens centered on strengthening attention to natural rewards may remediate reward processing deficits underpinning addictive behavior.
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NDT of fiber-reinforced composites with a new fiber-optic pump-probe laser-ultrasound system.
Photoacoustics
PUBLISHED: 06-01-2014
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Laser-ultrasonics is an attractive and powerful tool for the non-destructive testing and evaluation (NDT&E) of composite materials. Current systems for non-contact detection of ultrasound have relatively low sensitivity compared to contact peizotransducers. They are also expensive, difficult to adjust, and strongly influenced by environmental noise. Moreover, laser-ultrasound (LU) systems typically launch only about 50 firings per second, much slower than the kHz level pulse repetition rate of conventional systems. As demonstrated here, most of these drawbacks can be eliminated by combining a new generation of compact, inexpensive, high repetition rate nanosecond fiber lasers with new developments in fiber telecommunication optics and an optimally designed balanced probe beam detector. In particular, a modified fiber-optic balanced Sagnac interferometer is presented as part of a LU pump-probe system for NDT&E of aircraft composites. The performance of the all-optical system is demonstrated for a number of composite samples with different types and locations of inclusions.
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A qualitative study of acculturation and diabetes risk among urban immigrant Latinas: implications for diabetes prevention efforts.
Diabetes Educ
PUBLISHED: 05-28-2014
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The purpose of this qualitative study was to understand how acculturation influences diabetes risk among urban immigrant Latinas (Hispanic women).
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Laser-induced cavitation in nanoemulsion with gold nanospheres for blood clot disruption: in vitro results.
Opt Lett
PUBLISHED: 05-03-2014
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Optically activated cavitation in a nanoemulsion contrast agent is proposed for therapeutic applications. With a 56°C boiling point perfluorohexane core and highly absorptive gold nanospheres at the oil-water interface, cavitation nuclei in the core can be efficiently induced with a laser fluence below medical safety limits (70 mJ/cm2 at 1064 nm). This agent is also sensitive to ultrasound (US) exposure and can induce inertial cavitation at a pressure within the medical diagnostic range. Images from a high-speed camera demonstrate bubble formation in these nanoemulsions. The potential of using this contrast agent for blood clot disruption is demonstrated in an in vitro study. The possibility of simultaneous laser and US excitation to reduce the cavitation threshold for therapeutic applications is also discussed.
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4-Alkyloxyimino derivatives of uridine-5'-triphosphate: distal modification of potent agonists as a strategy for molecular probes of P2Y2, P2Y4, and P2Y6 receptors.
J. Med. Chem.
PUBLISHED: 04-18-2014
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Extended N(4)-(3-arylpropyl)oxy derivatives of uridine-5'-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N(4)-(3-phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N(4)-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y2R, 47 nM; P2Y4R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y2/4/6Rs, respectively, and specifically labeled cells expressing the P2Y6R. Thus, an extended N(4)-(3-arylpropyl)oxy group accessed a structurally permissive region on three Gq-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs.
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Robust estimates of environmental effects on population vital rates: an integrated capture-recapture model of seasonal brook trout growth, survival and movement in a stream network.
J Anim Ecol
PUBLISHED: 04-16-2014
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1.Modeling the effects of environmental change on populations is a key challenge for ecologists, particularly as the pace of change increases. Currently, modeling efforts are limited by difficulties in establishing robust relationships between environmental drivers and population responses. 2.We developed an integrated capture-recapture state-space model to estimate the effects of two key environmental drivers (stream flow and temperature) on demographic rates (body growth, movement, and survival) using a long-term (11 years), high resolution (individually tagged, sampled seasonally) dataset of brook trout (Salvelinus fontinalis) from four sites in a stream network. Our integrated model provides an effective context within which to estimate environmental driver effects because it takes full advantage of data by estimating (latent) state values for missing observations, because it propagates uncertainty among model components and because it accounts for the major demographic rates and interactions that contribute to annual survival. 3.We found that stream flow and temperature had strong effects on brook trout demography. Some effects, such as reduction in survival associated with low stream flow and high temperature during the summer season, were consistent across sites and age-classes, suggesting that they may serve as robust indicators of vulnerability to environmental change. Other survival effects varied across ages, sites, and seasons, indicating that flow and temperature may not be the primary drivers of survival in those cases. Flow and temperature also affected body growth rates; these responses were consistent across sites but differed dramatically between age-classes and seasons. Finally, we found that tributary and mainstem sites responded differently to variation in flow and temperature. 4.Annual survival (combination of survival and body growth across seasons) was insensitive to body growth and was most sensitive to flow (positive) and temperature (negative) in the summer and fall. 5.These observations, combined with our ability to estimate the occurrence, magnitude and direction of fish movement between these habitat types, indicated that heterogeneity in response may provide a mechanism providing potential resilience to environmental change. Given that the challenges we faced in our study are likely to be common to many intensive datasets, the integrated modeling approach could be generally applicable and useful. This article is protected by copyright. All rights reserved.
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Reductive functionalization of a rhodium(III)-methyl bond by electronic modification of the supporting ligand.
Dalton Trans
PUBLISHED: 04-10-2014
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Net reductive elimination (RE) of MeX (X = halide or pseudo-halide: Cl(-), CF3CO2(-), HSO4(-), OH(-)) is an important step during Pt-catalyzed hydrocarbon functionalization. Developing Rh(I/III)-based catalysts for alkane functionalization is an attractive alternative to Pt-based systems, but very few examples of RE of alkyl halides and/or pseudo-halides from Rh(III) complexes have been reported. Here, we compare the influence of the ligand donor strength on the thermodynamic potentials for oxidative addition and reductive functionalization using [(t)Bu3terpy]RhCl (1) {(t)Bu3terpy = 4,4',4''-tri-tert-butylpyridine} and [(NO2)3terpy]RhCl (2) {(NO2)3terpy = 4,4',4''-trinitroterpyridine}. Complex 1 oxidatively adds MeX {X = I(-), Cl(-), CF3CO2(-) (TFA(-))} to afford [(t)Bu3terpy]RhMe(Cl)(X) {X = I(-) (3), Cl(-) (4), TFA(-) (5)}. By having three electron-withdrawing NO2 groups, complex 2 does not react with MeCl or MeTFA, but reacts with MeI to yield [(NO2)3terpy]RhMe(Cl)(I) (6). Heating 6 expels MeCl along with a small quantity of MeI. Repeating this experiment but with excess [Bu4N]Cl exclusively yields MeCl, while adding [Bu4N]TFA yields a mixture of MeTFA and MeCl. In contrast, 3 does not reductively eliminate MeX under similar conditions. DFT calculations successfully predict the reaction outcome by complexes 1 and 2. Calorimetric measurements of [(t)Bu3terpy]RhI (7) and [(t)Bu3terpy]RhMe(I)2 (8) were used to corroborate computational models. Finally, the mechanism of MeCl RE from 6 was investigated via DFT calculations, which supports a nucleophilic attack by either I(-) or Cl(-) on the Rh-CH3 bond of a five-coordinate Rh complex.
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The association between obesity and health-related quality of life among urban Latinos.
Ethn Dis
PUBLISHED: 03-14-2014
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To examine differences in health-related quality of life (HRQL) by obesity status in a community-based sample of urban Latinos. To determine if sex moderates the relationship between HRQL and obesity status in this cohort.
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Enhanced osseous implant fixation with strontium-substituted bioactive glass coating.
Tissue Eng Part A
PUBLISHED: 03-07-2014
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The use of endosseous implants is firmly established in skeletal reconstructive surgery, with rapid and permanent fixation of prostheses being a highly desirable feature. Implant coatings composed of hydroxyapatite (HA) have become the standard and have been used with some success in prolonging the time to revision surgery, but aseptic loosening remains a significant issue. The development of a new generation of more biologically active coatings is a promising approach for tackling this problem. Bioactive glasses are an ideal candidate material due to the osteostimulative properties of their dissolution products. However, to date, they have not been formulated with stability to devitrification or thermal expansion coefficients (TECs) that are suitable for stable coating onto metal implants while still retaining their bioactive properties. Here, we present a strontium-substituted bioactive glass (SrBG) implant coating which has been designed to encourage peri-implant bone formation and with a TEC similar to that of HA. The coating can be successfully applied to roughened Ti6Al4V and after implantation into the distal femur and proximal tibia of twenty-seven New Zealand White rabbits for 6, 12, or 24 weeks, it produced no adverse tissue reaction. The glass dissolved over a 6 week period, stimulating enhanced peri-implant bone formation compared with matched HA coated implants in the contralateral limb. Furthermore, superior mechanical fixation was evident in the SrBG group after 24 weeks of implantation. We propose that this coating has the potential to enhance implant fixation in a variety of orthopedic reconstructive surgery applications.
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Mindfulness-Oriented Recovery Enhancement Ameliorates the Impact of Pain on Self-Reported Psychological and Physical Function Among Opioid-Using Chronic Pain Patients.
J Pain Symptom Manage
PUBLISHED: 03-03-2014
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Chronic pain impacts one-third of the U.S. population, and its effects are debilitating for individuals and costly to the medical system. Although opioids are commonly prescribed to address chronic pain, they confer risk for misuse and addiction in some patients and may not fully restore life function-particularly with regard to psychosocial factors. Because of the multiplicity of impacts that chronic pain may have on daily functioning, broad-spectrum behavioral interventions are needed.
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A new fiber-optic non-contact compact laser-ultrasound scanner for fast non-destructive testing and evaluation of aircraft composites.
J Appl Phys
PUBLISHED: 03-03-2014
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Laser ultrasonic (LU) inspection represents an attractive, non-contact method to evaluate composite materials. Current non-contact systems, however, have relatively low sensitivity compared to contact piezoelectric detection. They are also difficult to adjust, very expensive, and strongly influenced by environmental noise. Here, we demonstrate that most of these drawbacks can be eliminated by combining a new generation of compact, inexpensive fiber lasers with new developments in fiber telecommunication optics and an optimally designed balanced probe scheme. In particular, a new type of a balanced fiber-optic Sagnac interferometer is presented as part of an all-optical LU pump-probe system for non-destructive testing and evaluation of aircraft composites. The performance of the LU system is demonstrated on a composite sample with known defects. Wide-band ultrasound probe signals are generated directly at the sample surface with a pulsed fiber laser delivering nanosecond laser pulses at a repetition rate up to 76?kHz rate with a pulse energy of 0.6 mJ. A balanced fiber-optic Sagnac interferometer is employed to detect pressure signals at the same point on the composite surface. A- and B-scans obtained with the Sagnac interferometer are compared to those made with a contact wide-band polyvinylidene fluoride transducer.
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Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography.
Opt Lett
PUBLISHED: 02-25-2014
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We report on the use of phase-sensitive optical coherence tomography (PhS-OCT) to detect and track temporal and spatial shear wave propagation within tissue, induced by ultrasound radiation force. Kilohertz-range shear waves are remotely generated in samples using focused ultrasound emission and their propagation is tracked using PhS-OCT. Cross-sectional maps of the local shear modulus are reconstructed from local estimates of shear wave speed in tissue-mimicking phantoms. We demonstrate the feasibility of combining ultrasound radiation force and PhS-OCT to perform high-resolution mapping of the shear modulus.
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Synthesis of extended uridine phosphonates derived from an allosteric P2Y2 receptor ligand.
Molecules
PUBLISHED: 02-24-2014
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In this study we report the synthesis of C5/C6-fused uridine phosphonates that are structurally related to earlier reported allosteric P2Y2 receptor ligands. A silyl-Hilbert-Johnson reaction of six quinazoline-2,4-(1H,3H)-dione-like base moieties with a suitable ribofuranosephosphonate afforded the desired analogues after full deprotection. In contrast to the parent 5-(4-fluoropheny)uridine phosphonate, the present extended-base uridine phosphonates essentially failed to modulate the P2Y2 receptor.
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The disrupted basal ganglia and behavioural control: An integrative cross-domain perspective of spontaneous stereotypy.
Behav. Brain Res.
PUBLISHED: 02-19-2014
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Spontaneous stereotypic behaviour (SB) is common in many captive animal species, as well as in humans with some severe psychiatric disorders, and is often cited as being related to general basal ganglia dysfunction. Despite this assertion, there is little in the literature examining SB specifically in terms of the basal ganglia mechanics. In this review, we attempt to fill this gap by offering an integrative, cross-domain perspective of SB by linking what we currently understand about the SB phenotype with the ever-growing literature on the anatomy and functionality of the basal ganglia. After outlining current models of SB from different theoretical perspectives, we offer a broad but detailed overview of normally functioning basal ganglia mechanics, and attempt to link this with current neurophysiological evidence related to spontaneous SB. Based on this we present an empirically derived theoretical framework, which proposes that SB is the result of a dysfunctional action selection system that may reflect dysregulation of excitatory (direct) and inhibitory (indirect and hyperdirect) pathways as well as alterations in mechanisms of behavioural switching. This approach also suggests behaviours that specifically become stereotypic may reflect inbuilt low selection threshold behavioural sequences associated with early development and the species-specific ethogram or, low threshold behavioural sequences that are the result of stress-induced dopamine exposure at the time of performance.
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Effects of Mindfulness-Oriented Recovery Enhancement on reward responsiveness and opioid cue-reactivity.
Psychopharmacology (Berl.)
PUBLISHED: 02-08-2014
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Dysregulated reward processing is a hallmark feature of drug addiction; however, scant research has evaluated restructuring reward processing in the context of addiction treatment.
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Mindfulness-oriented recovery enhancement for chronic pain and prescription opioid misuse: results from an early-stage randomized controlled trial.
J Consult Clin Psychol
PUBLISHED: 02-03-2014
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Opioid pharmacotherapy is now the leading treatment for chronic pain, a problem that affects nearly one third of the U.S. population. Given the dramatic rise in prescription opioid misuse and opioid-related mortality, novel behavioral interventions are needed. The purpose of this study was to conduct an early-stage randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE), a multimodal intervention designed to simultaneously target mechanisms underpinning chronic pain and opioid misuse.
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Atomoxetine reduces anticipatory responding in a 5-choice serial reaction time task for adult zebrafish.
Psychopharmacology (Berl.)
PUBLISHED: 01-31-2014
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Deficits in impulse control are related to a number of psychiatric diagnoses, including attention deficit hyperactivity disorder, addiction, and pathological gambling. Despite increases in our knowledge about the underlying neurochemical and neuroanatomical correlates, understanding of the molecular and cellular mechanisms is less well established. Understanding these mechanisms is essential in order to move towards individualized treatment programs and increase efficacy of interventions. Zebrafish are a very useful vertebrate model for exploring molecular processes underlying disease owing to their small size and genetic tractability. Their utility in terms of behavioral neuroscience, however, hinges on the validation and publication of reliable assays with adequate translational relevance. Here, we report an initial pharmacological validation of a fully automated zebrafish version of the commonly used five-choice serial reaction time task using a variable interval pre-stimulus interval. We found that atomoxetine reduced anticipatory responses (0.6 mg/kg), whereas a high-dose (4 mg/kg) methylphenidate increased anticipatory responses and the number of trials completed in a session. On the basis of these results, we argue that similar neurochemical processes in fish as in mammals may control impulsivity, as operationally defined by anticipatory responses on a continuous performance task such as this, making zebrafish potentially a good model for exploring the molecular basis of impulse control disorders and for first-round drug screening.
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Primary purulent pericarditis and secondary endocarditis: a case report.
Cardiol Young
PUBLISHED: 01-31-2014
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Purulent pericarditis is a rare diagnosis to be made. It is exceedingly rare as a primary infection. We describe the case of an 18-month-old boy who presented with primary purulent pericarditis and developed a secondary endocarditis. Current literature on the subject is reviewed and discussed.
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The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 01-27-2014
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Exposure to moderate levels of ethanol during brain development has a number of effects on social behavior but the molecular mechanisms that mediate this are not well understood. Gaining a better understanding of these factors may help to develop therapeutic interventions in the future. Zebrafish offer a potentially useful model in this regard. Here, we introduce a zebrafish model of moderate prenatal ethanol exposure. Embryos were exposed to 20mM ethanol for seven days (48hpf-9dpf) and tested as adults for individual social behavior and shoaling. We also tested their basal anxiety with the novel tank diving test. We found that the ethanol-exposed fish displayed reductions in social approach and shoaling, and an increase in anxiety in the novel tank test. These behavioral differences corresponded to differences in hrt1aa, slc6a4 and oxtr expression. Namely, acute ethanol caused a spike in oxtr and ht1aa mRNA expression, which was followed by down-regulation at 7dpf, and an up-regulation in slc6a4 at 72hpf. This study confirms the utility of zebrafish as a model system for studying the molecular basis of developmental ethanol exposure. Furthermore, it proposes a putative developmental mechanism characterized by ethanol-induced OT inhibition leading to suppression of 5-HT and up-regulation of 5-HT1A, which leads, in turn, to possible homeostatic up-regulation of 5-HTT at 72hpf and subsequent imbalance of the 5-HT system.
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Shear wave pulse compression for dynamic elastography using phase-sensitive optical coherence tomography.
J Biomed Opt
PUBLISHED: 01-21-2014
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Assessing the biomechanical properties of soft tissue provides clinically valuable information to supplement conventional structural imaging. In the previous studies, we introduced a dynamic elastography technique based on phase-sensitive optical coherence tomography (PhS-OCT) to characterize submillimetric structures such as skin layers or ocular tissues. Here, we propose to implement a pulse compression technique for shear wave elastography. We performed shear wave pulse compression in tissue-mimicking phantoms. Using a mechanical actuator to generate broadband frequency-modulated vibrations (1 to 5 kHz), induced displacements were detected at an equivalent frame rate of 47 kHz using a PhS-OCT. The recorded signal was digitally compressed to a broadband pulse. Stiffness maps were then reconstructed from spatially localized estimates of the local shear wave speed. We demonstrate that a simple pulse compression scheme can increase shear wave detection signal-to-noise ratio (>12??dB gain) and reduce artifacts in reconstructing stiffness maps of heterogeneous media.
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Brief communication: Cineradiographic analysis of the chimpanzee (Pan troglodytes) talonavicular and calcaneocuboid joints.
Am. J. Phys. Anthropol.
PUBLISHED: 01-15-2014
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During terrestrial locomotion, chimpanzees exhibit dorsiflexion of the midfoot between midstance and toe-off of stance phase, a phenomenon that has been called the "midtarsal break." This motion is generally absent during human bipedalism, and in chimpanzees is associated with more mobile foot joints than in humans. However, the contribution of individual foot joints to overall foot mobility in chimpanzees is poorly understood, particularly on the medial side of the foot. The talonavicular (TN) and calcaneocuboid (CC) joints have both been suggested to contribute significantly to midfoot mobility and to the midtarsal break in chimpanzees. To evaluate the relative magnitude of motion that can occur at these joints, we tracked skeletal motion of the hindfoot and midfoot during passive plantarflexion and dorsiflexion manipulations using cineradiography. The sagittal plane range of motion was 38?±?10° at the TN joint and 14?±?8° at the CC joint. This finding indicates that the TN joint is more mobile than the CC joint during ankle plantarflexion-dorsiflexion. We suggest that the larger range of motion at the TN joint during dorsiflexion is associated with a rotation (inversion-eversion) across the transverse tarsal joint, which may occur in addition to sagittal plane motion.
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Primate energy expenditure and life history.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-13-2014
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Humans and other primates are distinct among placental mammals in having exceptionally slow rates of growth, reproduction, and aging. Primates' slow life history schedules are generally thought to reflect an evolved strategy of allocating energy away from growth and reproduction and toward somatic investment, particularly to the development and maintenance of large brains. Here we examine an alternative explanation: that primates' slow life histories reflect low total energy expenditure (TEE) (kilocalories per day) relative to other placental mammals. We compared doubly labeled water measurements of TEE among 17 primate species with similar measures for other placental mammals. We found that primates use remarkably little energy each day, expending on average only 50% of the energy expected for a placental mammal of similar mass. Such large differences in TEE are not easily explained by differences in physical activity, and instead appear to reflect systemic metabolic adaptation for low energy expenditures in primates. Indeed, comparisons of wild and captive primate populations indicate similar levels of energy expenditure. Broad interspecific comparisons of growth, reproduction, and maximum life span indicate that primates' slow metabolic rates contribute to their characteristically slow life histories.
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Mindfulness training targets neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface.
Front Psychiatry
PUBLISHED: 01-10-2014
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Prominent neuroscience models suggest that addictive behavior occurs when environmental stressors and drug-relevant cues activate a cycle of cognitive, affective, and psychophysiological mechanisms, including dysregulated interactions between bottom-up and top-down neural processes, that compel the user to seek out and use drugs. Mindfulness-based interventions (MBIs) target pathogenic mechanisms of the risk chain linking stress and addiction. This review describes how MBIs may target neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Empirical evidence is presented suggesting that MBIs ameliorate addiction by enhancing cognitive regulation of a number of key processes, including: clarifying cognitive appraisal and modulating negative emotions to reduce perseverative cognition and emotional arousal; enhancing metacognitive awareness to regulate drug-use action schema and decrease addiction attentional bias; promoting extinction learning to uncouple drug-use triggers from conditioned appetitive responses; reducing cue-reactivity and increasing cognitive control over craving; attenuating physiological stress reactivity through parasympathetic activation; and increasing savoring to restore natural reward processing. Treatment and research implications of our neurocognitive framework are presented. We conclude by offering a temporally sequenced description of neurocognitive processes targeted by MBIs through a hypothetical case study. Our neurocognitive framework has implications for the optimization of addiction treatment with MBIs.
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Nonlinear contrast enhancement in photoacoustic molecular imaging with gold nanosphere encapsulated nanoemulsions.
Appl Phys Lett
PUBLISHED: 01-05-2014
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A composite contrast agent, a nanoemulsion bead with assembled gold nanospheres at the interface, is proposed to improve the specific contrast of photoacoustic molecular imaging. A phase transition in the bead's core is induced by absorption of a nanosecond laser pulse with a fairly low laser fluence (?3.5 mJ/cm(2)), creating a transient microbubble through dramatically enhanced thermal expansion. This generates nonlinear photoacoustic signals with more than 10 times larger amplitude compared to that of a linear agent with the same optical absorption. By applying a differential scheme similar to ultrasound pulse inversion, more than 40?dB contrast enhancement is demonstrated with suppression of background signals.
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Parallel mechanisms for visual search in zebrafish.
PLoS ONE
PUBLISHED: 01-01-2014
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Parallel visual search mechanisms have been reported previously only in mammals and birds, and not animals lacking an expanded telencephalon such as bees. Here we report the first evidence for parallel visual search in fish using a choice task where the fish had to find a target amongst an increasing number of distractors. Following two-choice discrimination training, zebrafish were presented with the original stimulus within an increasing array of distractor stimuli. We found that zebrafish exhibit no significant change in accuracy and approach latency as the number of distractors increased, providing evidence of parallel processing. This evidence challenges theories of vertebrate neural architecture and the importance of an expanded telencephalon for the evolution of executive function.
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Trends and future challenges in sampling the deep terrestrial biosphere.
Front Microbiol
PUBLISHED: 01-01-2014
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Research in the deep terrestrial biosphere is driven by interest in novel biodiversity and metabolisms, biogeochemical cycling, and the impact of human activities on this ecosystem. As this interest continues to grow, it is important to ensure that when subsurface investigations are proposed, materials recovered from the subsurface are sampled and preserved in an appropriate manner to limit contamination and ensure preservation of accurate microbial, geochemical, and mineralogical signatures. On February 20th, 2014, a workshop on "Trends and Future Challenges in Sampling The Deep Subsurface" was coordinated in Columbus, Ohio by The Ohio State University and West Virginia University faculty, and sponsored by The Ohio State University and the Sloan Foundation's Deep Carbon Observatory. The workshop aims were to identify and develop best practices for the collection, preservation, and analysis of terrestrial deep rock samples. This document summarizes the information shared during this workshop.
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Endoscopic, Transoral, Reduction of Epiglottic Entrapment Via Wire Snare Technique.
Vet Surg
PUBLISHED: 01-01-2014
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To describe the use of a wire snare technique for epiglottic entrapment.
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Training medical students in the social determinants of health: the Health Scholars Program at Puentes de Salud.
Adv Med Educ Pract
PUBLISHED: 01-01-2014
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Given the large influence of social conditions on health, physicians may be more effective if they are trained to identify and address social factors that impact health. Despite increasing interest in teaching the social determinants of health in undergraduate medical education, few models exist.
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The Middle Miocene ape Pierolapithecus catalaunicus exhibits extant great ape-like morphometric affinities on its patella: inferences on knee function and evolution.
PLoS ONE
PUBLISHED: 01-01-2014
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The mosaic nature of the Miocene ape postcranium hinders the reconstruction of the positional behavior and locomotion of these taxa based on isolated elements only. The fossil great ape Pierolapithecus catalaunicus (IPS 21350 skeleton; 11.9 Ma) exhibits a relatively wide and shallow thorax with moderate hand length and phalangeal curvature, dorsally-oriented metacarpophalangeal joints, and loss of ulnocarpal articulation. This evidence reveals enhanced orthograde postures without modern ape-like below-branch suspensory adaptations. Therefore, it has been proposed that natural selection enhanced vertical climbing (and not suspension per se) in Pierolapithecus catalaunicus. Although limb long bones are not available for this species, its patella (IPS 21350.37) can potentially provide insights into its knee function and thus on the complexity of its total morphological pattern. Here we provide a detailed description and morphometric analyses of IPS 21350.37, which are based on four external dimensions intended to capture the overall patellar shape. Our results reveal that the patella of Pierolapithecus is similar to that of extant great apes: proximodistally short, mediolaterally broad and anteroposteriorly thin. Previous biomechanical studies of the anthropoid knee based on the same measurements proposed that the modern great ape patella reflects a mobile knee joint while the long, narrow and thick patella of platyrrhine and especially cercopithecoid monkeys would increase the quadriceps moment arm in knee extension during walking, galloping, climbing and leaping. The patella of Pierolapithecus differs not only from that of monkeys and hylobatids, but also from that of basal hominoids (e.g., Proconsul and Nacholapithecus), which display slightly thinner patellae than extant great apes (the previously-inferred plesiomorphic hominoid condition). If patellar shape in Pierolapithecus is related to modern great ape-like knee function, our results suggest that increased knee mobility might have originally evolved in relation to enhanced climbing capabilities in great apes (such as specialized vertical climbing).
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Formal aminocyanation of ?,?-unsaturated cyclic enones for the efficient synthesis of ?-amino ketones.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-01-2014
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Installation of amino functionality on organic molecules through direct C?N bond formation is an important research objective. To achieve this goal, a 1,2-aminocyanation reaction was developed. The reaction occurs through the formation of pyrazolines by means of a formal dipolar cycloaddition of cyclic ?,?-unsaturated ketones with lithium trimethylsilyldiazomethane followed by novel protonolytic N-N bond cleavage under mild conditions. This two-step process provides a diverse array of structurally complex free and mono-alkylated ?-amino ketones in excellent yields.
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The relationship between increased body mass index and frailty on falls in community dwelling older adults.
BMC Geriatr
PUBLISHED: 11-26-2013
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The global population is becoming older and more overweight. The inter-relationship between frailty and falls is often seen in the older adult and is associated with poor health outcomes. Little is known about this relationship for those with excess body mass. This study aimed to assess the relationships between BMI, frailty and falls.
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Implementing an E-prescribing system in outpatient mental health programs.
Adm Policy Ment Health
PUBLISHED: 11-20-2013
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This study describes the implementation and evaluation of an electronic prescription ordering system and feedback report in three community-based mental health outpatient agencies and the usefulness of the system in improving psychiatrists prescribing behavior. Using the e-prescribing system as a data collection tool, feedback on evidence based prescribing practices for patients diagnosed with schizophrenia spectrum disorder or major affective disorder was provided to agency directors and prescribers via a monthly report. The results of the project were that e-prescribing tools can be installed at a reasonable cost with a short start up period. Although the feedback intervention did not show a significant reduction in questionable prescribing patterns, we should continue to investigate how to best use HIT to improve safety, reduce costs, and enhance the quality of healthcare. A better understanding of what prescribers find useful and the reasons why they are prescribing non-evidenced based medications is needed if interventions of this type are to be effective. Given the availability of administrative claims data and electronic prescribing technology, considerable potential exists to provide useful information for monitoring and clinical decision making in public mental health systems.
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Cardiac diagnoses, procedures, and healthcare utilisation in inpatients with Ellis-van Creveld syndrome.
Cardiol Young
PUBLISHED: 10-31-2013
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Introduction Ellis-van Creveld syndrome is a rare condition associated with a very high incidence of congenital malformations of the heart. Prior reports have suggested increased morbidity and mortality following surgery for congenital malformations of the heart in patients with Ellis-van Creveld syndrome. Materials and methods The Pediatric Health Information System database, an administrative database containing data from 43 free-standing paediatric hospitals in North America, was queried to search for patients with the diagnostic code for Ellis-van Creveld syndrome between 2004 and 2011. Those patients who underwent cardiac procedures were compared with those who did not with respect to measures of healthcare utilisation.
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Alcohol exposure among pregnant women in sub-saharan Africa: a systematic review.
J Popul Ther Clin Pharmacol
PUBLISHED: 10-18-2013
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The prevalence of general alcohol use in many countries of sub-Saharan Africa (SSA) is high. However, research examining alcohol use in among pregnant women within this population is limited. A review of the current status of research examining the prevalence of alcohol exposed pregnancies (AEP) is required to inform future research aiming to decrease this occurrence and its subsequent socio-economic complications.
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A general, enantioselective synthesis of ?- and ?-fluoroamines.
Tetrahedron Lett.
PUBLISHED: 09-17-2013
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In this Letter, we describe a short, high yielding protocol for the enantioselective (87-96% ee) and general synthesis of ?-fluoroamines and previously difficult to access ?-fluoroamines from commercial aldehydes via organocatalysis.
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A three-dimensional musculoskeletal model of the chimpanzee (Pan troglodytes) pelvis and hind limb.
J. Exp. Biol.
PUBLISHED: 09-06-2013
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Musculoskeletal models have become important tools for studying a range of muscle-driven movements. However, most work has been in modern humans, with few applications in other species. Chimpanzees are facultative bipeds and our closest living relatives, and have provided numerous important insights into our own evolution. A chimpanzee musculoskeletal model would allow integration across a wide range of laboratory-based experimental data, providing new insights into the determinants of their locomotor performance capabilities, as well as the origins and evolution of human bipedalism. Here, we described a detailed three-dimensional (3D) musculoskeletal model of the chimpanzee pelvis and hind limb. The model includes geometric representations of bones and joints, as well as 35 muscle-tendon units that were represented using 44 Hill-type muscle models. Muscle architecture data, such as muscle masses, fascicle lengths and pennation angles, were drawn from literature sources. The model permits calculation of 3D muscle moment arms, muscle-tendon lengths and isometric muscle forces over a wide range of joint positions. Muscle-tendon moment arms predicted by the model were generally in good agreement with tendon-excursion estimates from cadaveric specimens. Sensitivity analyses provided information on the parameters that model predictions are most and least sensitive to, which offers important context for interpreting future results obtained with the model. Comparisons with a similar human musculoskeletal model indicate that chimpanzees are better suited for force production over a larger range of joint positions than humans. This study represents an important step in understanding the integrated function of the neuromusculoskeletal systems in chimpanzee locomotion.
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Three-dimensional moment arms and architecture of chimpanzee (Pan troglodytes) leg musculature.
J. Anat.
PUBLISHED: 09-05-2013
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The muscular and skeletal morphology of the chimpanzee ankle and foot differs from that of humans in many important respects. However, little information is available on the moment arms and architecture of the muscles that function around chimpanzee ankle and foot joints. The main goals of this study were to determine the influence of changes in leg and foot position on the moment arms of these muscle-tendon units (MTUs), and provide new measurements of their architecture. Three-dimensional moment arm data were collected from two adult, cadaveric Pan troglodytes specimens for 11 MTUs that cross the ankle and foot joints. Tendon-excursion measurements were made throughout the full range of plantarflexion-dorsiflexion (PF-DF) and eversion-inversion (EV-IN), including repeated measurements for mm. gastrocnemius at 0?°, 45?°, 90?° and 135?° of knee flexion. The total range of motion was calculated from three-dimensional joint motion data while ensuring that foot movement was restricted to a single plane. Measurements of muscle mass, fascicle length, pennation angle and physiological cross-sectional area were then collected for each MTU. Our results demonstrate that joint position has a significant effect on moment arm lengths, and that in some cases this effect is counterintuitive. These new data contribute to filling a significant gap in previously published chimpanzee moment arm data, providing a comprehensive characterization of the MTUs that move the chimpanzee ankle and foot joints. They also provide empirical support to the notion that chimpanzees have larger ranges of motion at these joints than humans. Comparison of osteometric estimates of moment arm lengths to direct tendon-excursion measures provides some guidance for the use of skeletal features in estimations of PF-DF moment arms. Finally, muscle architecture data are consistent with the findings of previous studies, and increase the sample size of the chimpanzee data that are currently available.
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Overshadowing of geometric cues by a beacon in a spatial navigation task.
Learn Behav
PUBLISHED: 08-13-2013
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In three experiments, we examined whether overshadowing of geometric cues by a discrete landmark (beacon) is due to the relative saliences of the cues. Using a virtual water maze task, human participants were required to locate a platform marked by a beacon in a distinctively shaped pool. In Experiment 1, the beacon overshadowed geometric cues in a trapezium, but not in an isosceles triangle. The longer escape latencies during acquisition in the trapezium control group with no beacon suggest that the geometric cues in the trapezium were less salient than those in the triangle. In Experiment 2, we evaluated whether generalization decrement, caused by the removal of the beacon at test, could account for overshadowing. An additional beacon was placed in an alternative corner. For the control groups, the beacons were identical; for the overshadow groups, they were visually unique. Overshadowing was again found in the trapezium. In Experiment 3, we tested whether the absence of overshadowing in the triangle was due to the geometric cues being more salient than the beacon. Following training, the beacon was relocated to a different corner. Participants approached the beacon rather than the trained platform corner, suggesting that the beacon was more salient. These results suggest that associative processes do not fully explain cue competition in the spatial domain.
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Behavioural phenotyping of casper mutant and 1-pheny-2-thiourea treated adult zebrafish.
Zebrafish
PUBLISHED: 07-20-2013
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Abstract The ability to visualise neural circuits in zebrafish in vivo is one of the most useful aspects of this model organism in neuroscience. To maintain the transparency of embryos, however, drugs, such as 1-pheyl-2-thiourea (PTU) must be added, or researchers can use mutants that do not develop pigment (e.g., the casper). The behavioural characteristics of such strains, however, have not been documented. Here, we tested adult zebrafish from the casper line, as well as wild-type (Tübingen, TU) and wild-types treated as embryos with PTU on three commonly used behavioural endpoints in neuroscience: novel tank test (similar to open-field in rodents), conditioned place preference for nicotine, and social cohesion (using a new method of cluster analysis). We found no differences between the casper and the TU, but the adult TU treated with PTU as embryos showed a marked increase in anxiety during the novel tank test. These data suggest that where possible, labs interested in analysis of developmental processes involved in adult phenotypes should avoid the use of PTU in favour of transparent mutants, such as casper.
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Emerging applications of conjugated polymers in molecular imaging.
Phys Chem Chem Phys
PUBLISHED: 07-18-2013
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In recent years, conjugated polymers have attracted considerable attention from the imaging community as a new class of contrast agent due to their intriguing structural, chemical, and optical properties. Their size and emission wavelength tunability, brightness, photostability, and low toxicity have been demonstrated in a wide range of in vitro sensing and cellular imaging applications, and have just begun to show impact in in vivo settings. In this Perspective, we summarize recent advances in engineering conjugated polymers as imaging contrast agents, their emerging applications in molecular imaging (referred to as in vivo uses in this paper), as well as our perspectives on future research.
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The downward spiral of chronic pain, prescription opioid misuse, and addiction: Cognitive, affective, and neuropsychopharmacologic pathways.
Neurosci Biobehav Rev
PUBLISHED: 07-02-2013
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Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction.
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Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients With Allergic Reactions or Anaphylaxis.
Ann Emerg Med
PUBLISHED: 07-01-2013
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Allergic reactions are common presentations to the emergency department (ED). An unknown proportion of patients will develop biphasic reactions, and patients are often monitored for prolonged periods to manage potential reactions. We seek to determine the incidence of clinically important biphasic reactions.
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Quantification, identification, and relevance of anti-human leukocyte antigen antibodies formed in association with the berlin heart ventricular assist device in children.
Transplantation
PUBLISHED: 06-20-2013
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Ventricular assist devices (VADs) are increasingly being used in pediatric patients to provide long-term cardiac support. One potential complication of VAD therapy is the development of antibodies directed against human leukocyte antigens (HLA). This phenomenon has not been well described with the Berlin Heart EXCOR VAD, the most commonly used VAD in pediatric patients.
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Shear modulus imaging by direct visualization of propagating shear waves with phase-sensitive optical coherence tomography.
J Biomed Opt
PUBLISHED: 06-03-2013
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We propose an integrated method combining low-frequency mechanics with optical imaging to map the shear modulus within the biological tissue. Induced shear wave propagating in tissue is tracked in space and time using phase-sensitive optical coherence tomography (PhS-OCT). Local estimates of the shear-wave speed obtained from tracking results can image the local shear modulus. A PhS-OCT system remotely records depth-resolved, dynamic mechanical waves at an equivalent frame rate of ?47??kHz with the high spatial resolution. The proposed method was validated by examining tissue-mimicking phantoms made of agar and light scattering material. Results demonstrate that the shear wave imaging can accurately map the elastic moduli of these phantoms.
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Regulation of phospholipase D activity and phosphatidic acid production after purinergic (P2Y6) receptor stimulation.
J. Biol. Chem.
PUBLISHED: 05-30-2013
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Phosphatidic acid (PA) is a lipid second messenger located at the intersection of several lipid metabolism and cell signaling events including membrane trafficking, survival, and proliferation. Generation of signaling PA has long been primarily attributed to the activation of phospholipase D (PLD). PLD catalyzes the hydrolysis of phosphatidylcholine into PA. A variety of both receptor-tyrosine kinase and G-protein-coupled receptor stimulations have been shown to lead to PLD activation and PA generation. This study focuses on profiling the PA pool upon P2Y6 receptor signaling manipulation to determine the major PA producing enzymes. Here we show that PLD, although highly active, is not responsible for the majority of stable PA being produced upon UDP stimulation of the P2Y6 receptor and that PA levels are tightly regulated. By following PA flux in the cell we show that PLD is involved in an initial increase in PA upon receptor stimulation; however, when PLD is blocked, the cell compensates by increasing PA production from other sources. We further delineate the P2Y6 signaling pathway showing that phospholipase C?3 (PLC?3), PLC?1, DGK? and PLD are all downstream of receptor activation. We also show that DGK? is a novel negative regulator of PLD activity in this system that occurs through an inhibitory mechanism with PKC?. These results further define the downstream events resulting in PA production in the P2Y6 receptor signaling pathway.
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Sequential Reactions of Trimethylsilyldiazomethane with 4-Alkenyl Ketones and Aldehydes Catalyzed by Lewis Bases.
Org. Lett.
PUBLISHED: 05-30-2013
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A sequence of a carbonyl addition between 4-alkenyl ketones and aldehydes with trimethylsilyldiazomethane followed by a 1,3-Brook rearrangement and an intramolecular 1,3-dipolar cycloaddition was promoted by Lewis bases tetrabutylammonium triphenyldifluorosilicate (TBAT) or potassium tert-butoxide (KO-t-Bu). Through these concatenated bond-forming processes, a variety of novel bi- and tricyclic ?(1)-pyrazolines were synthesized.
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Assessing empathy in antisocial youth: factor analytic and validation findings.
Psychol Rep
PUBLISHED: 05-10-2013
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Relatively few researchers have examined empathy among antisocial youth, although adolescents may differ greatly in the nature and frequency of their offending behavior. In this investigation, exploratory and confirmatory factor analysis were used (1) to derive a brief empathy scale from the Psychopathic Personality Inventory-Short Version; (2) to assess the construct validity, internal consistency, and potential clinical utility of the derived empathy subscale; and (3) to identify key sociodemographic, psychosocial, and behavioral correlates of empathy in delinquent youth. The 707 adolescent residents of 27 Missouri Division of Youth Services rehabilitation facilities had a mean age of 15.5 yr. (SD = 1.2) and most (87%) were boys. Analysis suggested that the new measure possesses adequate psychometric properties and may be a useful addition to clinical assessments of antisocial youth.
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Can molecular imaging enable personalized diagnostics? An example using magnetomotive photoacoustic imaging.
Ann Biomed Eng
PUBLISHED: 04-26-2013
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The advantages of photoacoustic (PA) imaging, including low cost, non-ionizing operation, and sub-mm spatial resolution at centimeters depth, make it a promising modality to probe nanoparticle-targeted abnormalities in real time at cellular and molecular levels. However, detecting rare cell types in a heterogeneous background with strong optical scattering and absorption remains a big challenge. For example, differentiating circulating tumor cells in vivo (typically fewer than 10 cells/mL for an active tumor) among billions of erythrocytes in the blood is nearly impossible. In this paper, a newly developed technique, magnetomotive photoacoustic (mmPA) imaging, which can greatly increase the sensitivity and specificity of sensing targeted cells or molecular interactions, is reviewed. Its primary advantage is suppression of background signals through magnetic enrichment/manipulation with simultaneous PA detection of magnetic contrast agent targeted objects. Results from phantom and in vitro studies demonstrate the capability of mmPA imaging to differentiate regions targeted with magnetic nanoparticles from the background, and to trap and sensitively detect targeted cells at a concentration of a single cell per milliliter in a flow system mimicking a human peripheral artery. This technique provides an example of the ways in which molecular imaging can potentially enable robust molecular diagnosis and treatment, and accelerate the translation of molecular medicine into the clinic.
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A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils.
Mol. Pharmacol.
PUBLISHED: 04-16-2013
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The nucleotide-sugar-activated P2Y14 receptor (P2Y14-R) is highly expressed in hematopoietic cells. Although the physiologic functions of this receptor remain undefined, it has been strongly implicated recently in immune and inflammatory responses. Lack of availability of receptor-selective high-affinity antagonists has impeded progress in studies of this and most of the eight nucleotide-activated P2Y receptors. A series of molecules recently were identified by Gauthier et al. (Gauthier et al., 2011) that exhibited antagonist activity at the P2Y14-R. We synthesized one of these molecules, a 4,7-disubstituted 2-naphthoic acid derivative (PPTN), and studied its pharmacological properties in detail. The concentration-effect curve of UDP-glucose for promoting inhibition of adenylyl cyclase in C6 glioma cells stably expressing the P2Y14-R was shifted to the right in a concentration-dependent manner by PPTN. Schild analyses revealed that PPTN-mediated inhibition followed competitive kinetics, with a KB of 434 pM observed. In contrast, 1 ?M PPTN exhibited no agonist or antagonist effect at the P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, or P2Y13 receptors. UDP-glucose-promoted chemotaxis of differentiated HL-60 human promyelocytic leukemia cells was blocked by PPTN with a concentration dependence consistent with the KB determined with recombinant P2Y14-R. In contrast, the chemotactic response evoked by the chemoattractant peptide fMetLeuPhe was unaffected by PPTN. UDP-glucose-promoted chemotaxis of freshly isolated human neutrophils also was blocked by PPTN. In summary, this work establishes PPTN as a highly selective high-affinity antagonist of the P2Y14-R that is useful for interrogating the action of this receptor in physiologic systems.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.