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Find video protocols related to scientific articles indexed in Pubmed.
Scale-up of organic reactions in ball mills: process intensification with regard to energy efficiency and economy of scale.
Faraday Discuss.
PUBLISHED: 11-20-2014
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The scale-up of the Knoevenagel-condensation between vanillin and barbituric acid carried out in planetary ball mills is investigated from an engineering perspective. Generally, the reaction proceeded in the solid state without intermediate melting and afforded selectively only one product. The reaction has been used as a model to analyze the influence and relationship of different parameters related to operation in planetary ball mills. From the viewpoint of technological parameters the milling ball diameter, dMB, the filling degree with respect to the milling balls' packing, ?MB,packing, and the filling degree of the substrates with respect to the void volume of the milling balls' packing, ?GS, have been investigated at different reaction scales. It was found that milling balls with small dMB lead to higher yields within shorter reaction time, treaction, or lower rotation frequency, rpm. Thus, the lower limit is set considering the technology which is available for the separation of the milling balls from the product after the reaction. Regarding ?MB,packing, results indicate that the optimal value is roughly 50% of the total milling beakers' volume, VB,total, independent of the reaction scale or reaction conditions. Thus, 30% of VB,total are taken by the milling balls. Increase of the initial batch sizes changes ?GS significantly. However, within the investigated parameter range no negative influence on the yield was observed. Up to 50% of VB,total can be taken over by the substrates in addition to 30% for the total milling ball volume. Scale-up factors of 15 and 11 were realized considering the amount of substrates and the reactor volume, respectively. Beside technological parameters, variables which influence the process itself, treaction and rpm, were investigated also. Variation of those allowed to fine-tune the reaction conditions in order to maximize the yield and minimize the energy intensity.
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New roles for the external globus pallidus in Basal Ganglia circuits and behavior.
J. Neurosci.
PUBLISHED: 11-14-2014
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The development of methodology to identify specific cell populations and circuits within the basal ganglia is rapidly transforming our ability to understand the function of this complex circuit. This mini-symposium highlights recent advances in delineating the organization and function of neural circuits in the external segment of the globus pallidus (GPe). Although long considered a homogeneous structure in the motor-suppressing "indirect-pathway," the GPe consists of a number of distinct cell types and anatomical subdomains that contribute differentially to both motor and nonmotor features of behavior. Here, we integrate recent studies using techniques, such as viral tracing, transgenic mice, electrophysiology, and behavioral approaches, to create a revised framework for understanding how the GPe relates to behavior in both health and disease.
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Chronic rhinosinusitis in patients requiring surgical repair of a midface fracture.
Ear Nose Throat J
PUBLISHED: 09-26-2014
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Midface fractures commonly occur following trauma to the face and may cause changes in the normal sinus outflow system. To the best of our knowledge, no study has examined the incidence of rhinosinusitis following midface fractures. We report the incidence of chronic rhinosinusitis in patients who underwent surgical repair of a midface fracture. Our evaluation tool was the 20-item Sino-Nasal Outcome Test quality-of-life survey (SNOT-20). We mailed a demographic survey and the SNOT-20 questionnaire to 486 eligible patients who had undergone surgical repair of either a midface (n = 234) or mandible (n = 252) fracture; we had intended to use the latter cohort as a control group. Of the 234 midface patients, 34 (14.5%) returned a usable survey, but only 7 of the 252 mandibular patients (2.8%) did so, which was not a sufficient number for analysis; therefore we used normative data obtained from another study for comparison purposes. The mean SNOT-20 score in our cohort was 24.15, which was similar to the 28.7 mean score in the control cohort of patients with rhinosinusitis. The highest mean scores for the individual components of the SNOT-20 were for "Wake up at night," "Lack of a good night's sleep," "Wake up tired," and "Frustrated/restless/irritable." The components that the most patients found bothersome were "Facial pain/pressure," "Need to blow nose," "Runny nose," and "Lack of a good night's sleep." We conclude that patients who experience a midface fracture have a much higher risk of developing chronic rhinosinusitis that negatively affects their long-term quality of life. These patients should be monitored with long-term follow-up and treated appropriately.
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High Plasma Erythropoietin Levels are Associated With Prolonged Coma Duration and Increased Mortality in Children With Cerebral Malaria.
Clin. Infect. Dis.
PUBLISHED: 09-16-2014
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?Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes.
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A little spin on the side: solvent and temperature dependent paramagnetism in [Ru(II)(bpy)2(phendione)](2+).
Dalton Trans
PUBLISHED: 09-12-2014
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Solvent and temperature dependent paramagnetism is reported for the complex [Ru(II)(bpy)2(phendione)](PF6)2 (bpy = 2,2'-bipyridine, phendione = 1,10-phenanthroline-5,6-dione), . Magnetometry, (1)H-NMR, EPR and substituent effects confirm that the paramagnetic character is localized on the phendione ligand, and arises due to mixing of the MLCT excited state with an open shell triplet state on the phendione moiety, a process that is most likely driven by aromatization. The stabilized open shell phendione structure, in which the triplet lies lower in energy than the singlet, can then be thermally populated from the ground state of the complex. This process is facilitated by admixture of singlet character from the MLCT state. Paramagnetic behavior is absent in the free phendione ligand, and disappears in the presence of Lewis acids and in the presence of water due to hydrogen bonding (or hydrate formation at sufficient water concentrations). Control experiments rule out the presence of monoradicals such as semiquinone anions. Implications for spin filtering, sensing, and other electronic applications using such structures are discussed.
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Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy.
J. Med. Chem.
PUBLISHED: 08-21-2014
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The synthesis and characterization of a series of selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation antagonists that inhibit all modes of TRPV1 activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models and only partially block acid activation of TRPV1. Advancing the SAR of this series led to the eventual identification of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an analogue that possesses excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents.
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An analysis of clinical consultation activities in clinical pathology: who requests help and why.
Am. J. Clin. Pathol.
PUBLISHED: 08-16-2014
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To examine the distribution of callers who made consultation requests and to identify associations between caller categories and consultation topics.
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A cost-effectiveness analysis of cell free DNA as a replacement for serum screening for Down syndrome.
Prenat. Diagn.
PUBLISHED: 08-07-2014
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The aim of this article is to determine the cost effectiveness of cell free DNA (cfDNA) as a replacement for integrated screening using a societal cost perspective.
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Dopamine modulation of learning and memory in the prefrontal cortex: insights from studies in primates, rodents, and birds.
Front Neural Circuits
PUBLISHED: 08-05-2014
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In this review, we provide a brief overview over the current knowledge about the role of dopamine transmission in the prefrontal cortex during learning and memory. We discuss work in humans, monkeys, rats, and birds in order to provide a basis for comparison across species that might help identify crucial features and constraints of the dopaminergic system in executive function. Computational models of dopamine function are introduced to provide a framework for such a comparison. We also provide a brief evolutionary perspective showing that the dopaminergic system is highly preserved across mammals. Even birds, following a largely independent evolution of higher cognitive abilities, have evolved a comparable dopaminergic system. Finally, we discuss the unique advantages and challenges of using different animal models for advancing our understanding of dopamine function in the healthy and diseased brain.
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Toward Distinguishing Recurrent Tumor From Radiation Necrosis: DWI and MTC in a Gamma Knife-Irradiated Mouse Glioma Model.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 08-04-2014
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Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose.
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Validation of separated source frequency delivery for a fiber-coupled heterodyne displacement interferometer.
Opt Lett
PUBLISHED: 08-01-2014
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The use of optical fibers presents several advantages with respect to free-space optical transport regarding source-frequency delivery to individual heterodyne interferometers. Unfortunately, fiber delivery to individual coaxial heterodyne interferometers leads to an increase of (periodic) nonlinearity in the measurement, because transporting coaxial frequencies through one optical fiber leads to frequency mixing. Coaxial beams thus require delivery via free-space transportation methods. In contrast, the heterodyne interferometer concept discussed in this Letter is based on separated source frequencies, which allow for fiber delivery without additional nonlinearity. This investigation analyzes the influence of external disturbances acting on the two fibers during delivery, causing asymmetry in phase between the two fibers (first-order effect), and irradiance fluctuations (second-order effect). Experiments using electro-optic phase modulation and acousto-optic irradiance modulation confirmed that the interferometer-concept can measure with sub-nanometer uncertainty using fiber delivered source frequencies, enabling fully fiber-coupled heterodyne displacement interferometers.
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Neuropathology and genetics of cerebroretinal vasculopathies.
Brain Pathol.
PUBLISHED: 07-11-2014
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Cerebroretinal vasculopathy (CRV) and the related diseases hereditary endotheliopathy with retinopathy, neuropathy, and stroke (HERNS), hereditary vascular retinopathy (HVR) and hereditary systemic angiopathy (HSA) [subsequently combined as retinovasculopathy and cerebral leukodystrophy (RVCL)] are devastating autosomal-dominant disorders of early to middle-age onset presenting with a core constellation of neurologic and ophthalmologic findings. This family of diseases is linked by specific mutations targeting a core region of a gene. Frameshift mutations in the carboxyl-terminus of three prime exonuclease-1 (TREX1), the major mammalian 3' to 5' DNA exonuclease on chromosome 3p21.1-p21.3, result in a systemic vasculopathy that follows an approximately 5-year course leading to death secondary to progressive neurologic decline, with sometimes a more protracted course in HERNS. Neuropathological features include a fibrinoid vascular necrosis or thickened hyalinized vessels associated with white matter ischemia, necrosis and often striking dystrophic calcifications. Ultrastructural studies of the vessel walls often demonstrate unusual multilaminated basement membranes.
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Perceived damage and areas of needed research for wildlife pests of California agriculture.
Integr Zool
PUBLISHED: 06-24-2014
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Many wildlife species cause extensive damage to a variety of agricultural commodities in California, with estimates of damage in the hundreds of millions annually. Given the limited availability of resources to solve all human-wildlife conflicts, we should focus management efforts on issues that provide the greatest benefit to agricultural commodities in California. This survey provides quantitative data on research needs to better guide future efforts in developing more effective, practical and appropriate methods for managing these species. We found that ground squirrels, pocket gophers, birds, wild pigs, coyotes and voles were the most common agricultural wildlife pest species in California. The damage caused by these species could be quite high, but varied by agricultural commodity. For most species, common forms of damage included loss of crop production and direct death of the plant, although livestock depredation was the greatest concern for coyotes. Control methods used most frequently and those deemed most effective varied by pest species, although greater advancements in control methods were listed as a top research priority for all species. Collectively, the use of toxicants, biocontrol and trapping were the most preferred methods for control, but this varied by species. In general, integrated pest management practices were used to control wildlife pests, with a special preference for those approaches that were efficacious and quick and inexpensive to apply. This information and survey design should be useful in establishing research and management priorities for wildlife pest species in California and other similar regions.
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Midterm clinical and radiographic results of the medial pivot total knee system.
Int Orthop
PUBLISHED: 06-09-2014
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The ADVANCE® Medial Pivot Knee System was designed with a highly congruent medial compartment and a less conforming lateral compartment to more closely mimic the kinematics of the normal knee. The purpose of this study was to evaluate the midterm clinical and radiographic outcomes of this total knee arthroplasty (TKA) system.
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Modeling inheritance of phase precession in the hippocampal formation.
J. Neurosci.
PUBLISHED: 05-30-2014
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Spatial information about the environment is encoded by the activity of place and grid cells in the hippocampal formation. As an animal traverses a cell's firing field, action potentials progressively shift to earlier phases of the theta oscillation (6-10 Hz). This "phase precession" is observed also in the prefrontal cortex and the ventral striatum, but mechanisms for its generation are unknown. However, once phase precession exists in one region, it might also propagate to downstream regions. Using a computational model, we analyze such inheritance of phase precession, for example, from the entorhinal cortex to CA1 and from CA3 to CA1. We find that distinctive subthreshold and suprathreshold features of the membrane potential of CA1 pyramidal cells (Harvey et al., 2009; Mizuseki et al., 2012; Royer et al., 2012) can be explained by inheritance and that excitatory input is essential. The model explains how inhibition modulates the slope and range of phase precession and provides two main testable predictions. First, theta-modulated inhibitory input to a CA1 pyramidal cell is not necessary for phase precession. Second, theta-modulated inhibitory input on its own generates membrane potential peaks that are in phase with peaks of the extracellular field. Furthermore, we suggest that the spatial distribution of field centers of a population of phase-precessing input cells determines, not only the place selectivity, but also the characteristics of phase precession of the targeted output cell. The inheritance model thus can explain why phase precession is observed throughout the hippocampal formation and other areas of the brain.
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An analysis of clinical consultation activities in clinical chemistry: implications for transformation and resident training in chemical pathology.
Arch. Pathol. Lab. Med.
PUBLISHED: 05-03-2014
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Clinical consultation is a key role of pathologists. Many have advocated that pathologists expand their consulting activities to improve laboratory utilization. Although many have suggested that residency programs need to provide experience in clinical consultation, little has been written on the nature of consultation or on the methods of training.
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Impact of rapid on-site evaluation on the adequacy of endoscopic-ultrasound guided fine-needle aspiration of solid pancreatic lesions: a systematic review and meta-analysis.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-01-2014
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Rapid on-site evaluation (ROSE) has the potential to improve adequacy rates for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic lesions, but its impact is context-dependent. No studies exist that summarize the relationship between ROSE, number of needle passes, and resulting adequacy rates.
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Lesions of the avian pancreas.
Vet Clin North Am Exot Anim Pract
PUBLISHED: 04-08-2014
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Although not well described, occasional reports of avian exocrine and endocrine pancreatic disease are available. This article describes the lesions associated with common diseases of the avian pancreas reported in the literature and/or seen by the authors.
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Thrombin-mediated degradation of parathyroid hormone in serum tubes.
Clin. Chim. Acta
PUBLISHED: 04-07-2014
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Intact parathyroid hormone (PTH) tests are frequently sandwich immunoassays. Enzymes that cleave PTH may cause falsely lower PTH results. The objective of this study was to determine whether bovine thrombin in Becton Dickinson (BD) Vacutainer rapid serum tubes™ (RSTs) may lead to PTH results that are lower than in plasma separator tube™ (PST) or serum separator tube™ (SST) collections.
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A GSK-3? inhibitor protects against radiation necrosis in mouse brain.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-07-2014
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To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3?, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model.
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Heterodyne displacement interferometer, insensitive for input polarization.
Opt Lett
PUBLISHED: 04-02-2014
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Periodic nonlinearity (PNL) in displacement interferometers is a systematic error source that limits measurement accuracy. The PNL of coaxial heterodyne interferometers is highly influenced by the polarization state and orientation of the source frequencies. In this Letter, we investigate this error source and discuss two interferometer designs, designed at TU Delft, that showed very low levels of PNL when subjected to any polarization state and/or polarization orientation. In the experiments, quarter-wave plates (qwps) and half-wave plates (hwps) were used to manipulate the polarization state and polarization orientation, respectively. Results from a commercial coaxial system showed first-order PNL exceeding 10 nm (together with higher order PNL) when the system ceased operation at around ±15°??hwp rotation or ±20°??qwp rotation. The two "Delft interferometers," however, continued operation beyond these maxima and obtained first-order PNLs in the order of several picometers, without showing higher order PNLs. The major advantage of these interferometers, beside their high linearity, is that they can be fully fiber coupled and thus allow for a modular system buildup.
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Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility.
J. Clin. Invest.
PUBLISHED: 03-20-2014
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Multiple sclerosis (MS) is an inflammatory disease of the CNS that is characterized by BBB dysfunction and has a much higher incidence in females. Compared with other strains of mice, EAE in the SJL mouse strain models multiple features of MS, including an enhanced sensitivity of female mice to disease; however, the molecular mechanisms that underlie the sex- and strain-dependent differences in disease susceptibility have not been described. We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that regulates BBB permeability by destabilizing adherens junctions. S1PR2 expression was increased in disease-susceptible regions of the CNS of both female SJL EAE mice and female patients with MS compared with their male counterparts. Pharmacological blockade or lack of S1PR2 signaling decreased EAE disease severity as the result of enhanced endothelial barrier function. Enhanced S1PR2 signaling in an in vitro BBB model altered adherens junction formation via activation of Rho/ROCK, CDC42, and caveolin endocytosis-dependent pathways, resulting in loss of apicobasal polarity and relocation of abluminal CXCL12 to vessel lumina. Furthermore, S1PR2-dependent BBB disruption and CXCL12 relocation were observed in vivo. These results identify a link between S1PR2 signaling and BBB polarity and implicate S1PR2 in sex-specific patterns of disease during CNS autoimmunity.
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Anti-VEGF antibodies mitigate the development of radiation necrosis in mouse brain.
Clin. Cancer Res.
PUBLISHED: 03-19-2014
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To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model.
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Diagnostic accuracy and clinical utility of biopsy in musculoskeletal lesions: a comparison of fine-needle aspiration, core, and open biopsy techniques.
Diagn. Cytopathol.
PUBLISHED: 03-19-2014
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Selection of biopsy technique for musculoskeletal lesions is complex. Fine-needle aspiration (FNA) is uncommonly used due to concerns regarding accuracy. We compared diagnostic accuracy of FNA, core, and open biopsy in a series of musculoskeletal lesions. Records of the University of Utah were searched for biopsy and resection specimens of musculoskeletal lesions. Results of corresponding imaging studies were obtained. Biopsy and FNA diagnoses were correlated with resection diagnoses. For each technique, diagnostic accuracy, utility, and frequency of subsequent biopsy were calculated. Open biopsy had the highest diagnostic accuracy (89%) followed by FNA (82%) and core biopsy (78%). Clinically significant errors occurred with all methods. The likelihood of an open biopsy being performed was affected by prior performance of an FNA or core biopsy and by diagnostic imaging and FNA results.
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The fluorescence intermittency for quantum dots is not power-law distributed: a luminescence intensity resolved approach.
ACS Nano
PUBLISHED: 03-07-2014
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The photoluminescence (PL) of single emitters like semiconductor quantum dots (QDs) shows PL intermittency, often called blinking. We explore the PL intensities of single CdSe/ZnS QDs in polystyrene (PS), on polyvenylalcohol (PVA), and on silicon oxide (SiOx) by the change-point analysis (CPA). By this, we relate results from the macrotime (sub-ms to 1000 s) and the microtime (0.1-100 ns) range to discrete PL intensities. We conclude that the intensity selected "on"-times in the ms range correspond to only a few (discrete) switching times, while the PL decays in the ns range are multiexponential even with respect to the same selected PL intensity. Both types of relaxation processes depend systematically on the PL intensity in course of a blinking time trace. The overall distribution of on-times does not follow a power law contrary to what has often been reported but can be compiled into 3-4 characteristic on-times. The results can be explained by the recently suggested multiple recombination centers model. Additionally, we can identify a well-defined QD state with a very low PL intensity above the noise level, which we assign to the strongly quenched exciton state. We describe our findings by a model of a hierarchical sequence of hole and electron trapping. Blinking events are the consequence of slow switching processes among these states and depend on the physicochemical properties of the heterogeneous nanointerface of the QDs.
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Significance of the diagnostic categories "atypical" and "suspicious for malignancy" in the cytologic diagnosis of solid pancreatic masses.
Diagn. Cytopathol.
PUBLISHED: 02-28-2014
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Endoscopic ultrasound guided (EUS) fine-needle aspiration (FNA) investigation of solid pancreatic lesions has been shown to have good sensitivity and specificity. Many lesions can be definitely classified as benign or malignant but some can only be cytologically classified as "atypical" or "suspicious for malignancy". Risk for malignancy in these indeterminate categories has not been well categorized. The cytology records of four University Medical centers were searched for all EUS guided FNAs of solid pancreatic lesions. All cases with a diagnosis of "atypical", or "suspicious for malignancy" were selected for analysis when histologic biopsy or over 18 months clinical follow-up was available. Two hundred and ninety-two cases with a diagnosis of "atypical" or "suspicious for malignancy" and adequate follow-up were obtained from the combined data of the four institutions. The percentage malignant for the categories "atypical" and "suspicious for malignancy" were 79.2 and 96.3%, respectively. If the category "atypical" was classified as benign and "suspicious for malignancy" was classified as malignant, the resulting positive predictive value was 96.3 (95% CI: 92.6-98.5) and the negative predictive value 20.8 (95% CI: 13.4-30.0). The categories of "atypical" and "suspicious for malignancy" stratify risk for malignancy in a fashion, which may aid in patient counseling and selection of follow-up protocols. Classification of "suspicious for malignancy" as malignant optimizes diagnostic sensitivity and specificity.
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Decompression illness in divers treated in Auckland, New Zealand, 1996-2012.
Diving Hyperb Med
PUBLISHED: 01-03-2014
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The treatment of divers for decompression illness (DCI) in Auckland, New Zealand, has not been described since 1996, and subsequent trends in patient numbers and demographics are unmeasured.
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Optimized immunohistochemical panel to differentiate myeloid sarcoma from blastic plasmacytoid dendritic cell neoplasm.
Mod. Pathol.
PUBLISHED: 01-03-2014
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Myeloid sarcoma (MS) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) can be difficult to distinguish morphologically, even with the use of extensive immunohistochemical studies. Three new research markers, myxovirus A (MxA), CLA/CD162, and CD303/BDCA-2, have been reported to be positive in BPDCN, but their clinical utility has never been tested. We compared these markers to other antibodies that have been used traditionally to distinguish MS from BPDCN to assess the utility of these newer antibodies in differential diagnosis. Formalin-fixed, paraffin-embedded tissue sections of 23 MS and 17 BPDCN cases were assessed using immunohistochemical analysis for CD4, CD14, CD33, CD43, CD56, CD68, CD123, CD163, myeloperoxidase, lysozyme, terminal deoxynucleotidyl transferase (TdT), T-cell leukemia 1 (TCL-1), MxA, cutaneous lymphocyte-associated antigen (CLA)/CD162, and blood dendritic cell antigen 2 (BDCA2)/CD303. We identified antibodies with a high predictive value of ? 90% and used these markers to develop an approach to classification using specific staining criteria. Diagnostic classification criteria were based on staining patterns of one or more of the seven markers. BPDCN was associated with positive staining for CD56, TdT, or TCL1, or negative staining for lysozyme. MS was associated with positive staining for lysozyme or myeloperoxidase, or negative staining for CD56, CD123, myxovirus, or TCL1. The immunohistochemical staining patterns observed using a panel that includes MPO, CD56, CD123, TCL1, TdT, and MxA, are predictive of MS or BPDCN. In this study, neither CD162 nor CD303 had good predictive value in distinguishing MS from BPDCN.
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Diagnostic accuracy studies of fine-needle aspiration show wide variation in reporting of study population characteristics: implications for external validity.
Arch. Pathol. Lab. Med.
PUBLISHED: 01-01-2014
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Study comparisons rest on the assessment of applicability or external validity. Population characteristics are an important component of external validity and, although there has been a heightened awareness of deficiencies in reporting in diagnostic test accuracy (DTA) studies, the reporting of populations in DTA studies has not been investigated.
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Gastrointestinal stromal tumors: clinical significance of p53 expression, MDM2 amplification, and KIT mutation status.
Appl. Immunohistochem. Mol. Morphol.
PUBLISHED: 11-20-2013
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Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Clinical behavior is best predicted by size and mitotic count (risk index). KIT and platelet-derived growth factor receptor ? (PDGFRA) mutations have therapeutic and prognostic value but few other prognostically significant molecular markers have been identified. We investigated the prognostic value of p53 protein expression and MDM2 gene amplification in a series of GISTs.
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Fine-needle aspiration cytology for the diagnosis of metastatic melanoma: systematic review and meta-analysis.
Am. J. Clin. Pathol.
PUBLISHED: 10-15-2013
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To perform a thorough review and meta-analysis of studies that have shown non-image-guided fine-needle aspiration cytology (FNAC) to be highly sensitive and specific for assessing questionable metastatic melanoma to lymph nodes.
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Malignancy risk associated with diagnostic categories defined by the Papanicolaou Society of Cytopathology pancreaticobiliary guidelines.
Cancer Cytopathol
PUBLISHED: 08-30-2013
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Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently the predominant method for obtaining a preoperative tissue diagnosis for pancreatic lesions suspicious for malignancy. The diagnostic sensitivity and specificity of EUS-FNA are well documented, but malignancy risk associated with the diagnostic categories proposed by the Papanicolaou Society of Cytopathology is poorly defined.
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Development of an equation to correct for hemolysis in direct bilirubin measurements.
Clin. Chim. Acta
PUBLISHED: 08-19-2013
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Direct bilirubin is measured for the investigation of pediatric and adult jaundice. Package inserts suggest that hemolysis decreases direct bilirubin measurements, but no published studies have adequately described the extent of interference.
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Ultrasound-guided core needle biopsy of salivary gland lesions: A systematic review and meta-analysis.
Laryngoscope
PUBLISHED: 07-12-2013
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To obtain summary estimates of the sensitivity and specificity of core needle biopsy for assessment of salivary gland lesions and to investigate sources of variation in accuracy between study locations.
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Practice Trends in the Utilization of Intraoperative Neurophysiological Monitoring in Pediatric Neurosurgery as a Function of Complication Rate, and Patient-, Surgeon-, and Procedure-Related Factors.
World Neurosurg
PUBLISHED: 05-27-2013
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Higher benchmarks in safety for patients undergoing neurosurgery have been introduced. With these principles, new tools and techniques were established, including intraoperative neurophysiological monitoring (IONM). Current trends as a function of patient-, surgeon-, and procedure-related factors, and complication rates in the utilization of IONM as an adjunct to the practice of pediatric neurosurgery have not been previously investigated.
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Assessment of orally dosed commercial silver nanoparticles on human ex vivo platelet aggregation.
Nanotoxicology
PUBLISHED: 05-02-2013
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Abstract Enhanced in vitro human and ex vivo rat platelet aggregation from direct exposure to silver nanoparticles is previously reported. Given the increasing human use of engineered silver nanoscale products, platelet aggregation prompted by silver nanoparticles may contribute to human cardiovascular events. To understand how direct washed platelet exposure to silver nanoparticles translates to ex vivo platelet aggregation, the authors conducted a placebo-controlled, single-blind, dose-monitored, cross-over study design in 18 healthy human volunteers. After 2 weeks of daily oral silver nanoparticle ingestion, platelet aggregation was evaluated by light transmission aggregometry in response to collagen and ADP agonists, both at baseline and after silver nanoparticle or placebo diluent oral dosing. Final percent aggregation (PA) and the changes in PA were determined using a paired design (i.e., active and placebo solutions). Enhanced ex vivo platelet activation was not detectable at peak serum silver concentrations <10 µg/L. Further studies of colloidal silver nanoparticles on human platelet activities are warranted.
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Quality appraisal of diagnostic accuracy studies in fine-needle aspiration cytology: a survey of risk of bias and comparability.
Arch. Pathol. Lab. Med.
PUBLISHED: 04-03-2013
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The quality of diagnostic accuracy studies is determined by 2 key factors: risk of bias and comparability. Bias can distort accuracy estimates and poor reporting impairs comparability. While diagnostic accuracy studies for fine-needle aspiration cytology (FNAC) are frequently published, the methodologic issues associated with this body of literature have never been reviewed.
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Understanding sources of bias in diagnostic accuracy studies.
Arch. Pathol. Lab. Med.
PUBLISHED: 04-03-2013
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Accuracy is an important feature of any diagnostic test. There has been an increasing awareness of deficiencies in study design that can create bias in estimates of test accuracy. Many pathologists are unaware of these sources of bias.
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Rapid on-site evaluation reduces needle passes in endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: a risk-benefit analysis.
Dig. Dis. Sci.
PUBLISHED: 03-25-2013
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The effectiveness of endoscopic ultrasound-guided fine-needle aspiration increases with the number of needle passes but needle passes are also associated with increased risk of adverse events. The trade-off between needle passes and adequacy has not been well-characterized.
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Canceling actions involves a race between basal ganglia pathways.
Nat. Neurosci.
PUBLISHED: 03-22-2013
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Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons exhibited low-latency responses to Stop cues, irrespective of whether actions were canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) only responded to Stop cues in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral core subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with stopping requiring Stop-cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return.
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Rapid onsite evaluation improves the adequacy of fine-needle aspiration for thyroid lesions: a systematic review and meta-analysis.
Thyroid
PUBLISHED: 03-18-2013
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Fine-needle aspiration (FNA) with ultrasonography guidance is one of the optimal techniques for the diagnostic evaluation of thyroid nodules. A significant subset of thyroid FNAs continues to be inadequate for interpretation, which potentially leads to increased costs from repeat aspirations. Numerous studies have been published regarding the influence of rapid onsite evaluation (ROSE) by cytopathologists on thyroid FNAs, some indicating that FNA is more likely to be adequate for interpretation with ROSE, while others refute this idea. To our knowledge, no meta-analysis of the literature on this subject has been undertaken.
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Photoluminescence emission and Raman response of monolayer MoS?, MoSe?, and WSe?.
Opt Express
PUBLISHED: 03-14-2013
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We mechanically exfoliate mono- and few-layers of the transition metal dichalcogenides molybdenum disulfide, molybdenum diselenide, and tungsten diselenide. The exact number of layers is unambiguously determined by atomic force microscopy and high-resolution Raman spectroscopy. Strong photoluminescence emission is caused by the transition from an indirect band gap semiconductor of bulk material to a direct band gap semiconductor in atomically thin form.
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Utility of preoperative ultrasound for predicting pN2 or higher stage axillary lymph node involvement in patients with newly diagnosed breast cancer.
AJR Am J Roentgenol
PUBLISHED: 02-26-2013
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The objective of our study was to report the positive predictive value (PPV) of ultrasound of the axilla to predict pN2 or higher disease in breast cancer patients.
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Multifocal radiculoneuropathy during ipilimumab treatment of melanoma.
Muscle Nerve
PUBLISHED: 02-25-2013
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Ipilimumab, a monoclonal anti-CTLA-4 antibody, is used to treat melanoma. Neuromuscular side effects, possibly autoimmune, may occur.
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Risk-benefit analysis of sampling methods for fine-needle aspiration cytology: a mathematical modeling approach.
Am. J. Clin. Pathol.
PUBLISHED: 02-23-2013
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The effectiveness of fine-needle aspiration (FNA) increases with the number of needle passes, but needle passes are also associated with increased risk of adverse events. The trade-off between needle passes and adequacy has not been well characterized. Clinical studies are limited because of their inherent variability and limited sample size. We developed mathematical models to compare the performance of a variety of sampling protocols under a wide range of conditions. Specifically, we compared the performance of sampling methods using a fixed number of needle passes with sampling methods using a rapid onsite evaluation (ROSE) with a variable number of needle passes. Variable sampling with ROSE generally required fewer needle passes than fixed sample size policies to achieve a desired adequacy rate. Variable sampling policies using ROSE achieve greater per-case adequacy with fewer needle passes than sampling policies using a fixed number of passes if assessor accuracy is high.
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The influence of rapid onsite evaluation on the adequacy rate of fine-needle aspiration cytology: a systematic review and meta-analysis.
Am. J. Clin. Pathol.
PUBLISHED: 02-23-2013
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Rapid onsite evaluation (ROSE) has the potential to improve the adequacy rates of fine-needle aspiration (FNA) cytology. Studies have obtained variable results on the influence of ROSE. We conducted a systematic review and meta-analysis of studies on the influence of ROSE on FNA adequacy. We synthesized evidence across all anatomic locations. We only included studies that contained a control arm and compared cohorts with ROSE against cohorts without ROSE at a single location. We screened 2,179 studies and identified 25 studies that met our inclusion criteria. On average, ROSE improves the adequacy rate by 12%, but there was considerable variability across studies. The adequacy rate with ROSE depends on the non-ROSE adequacy rate. Sixty-five percent of the variability in the adequacy rate with ROSE was found to occur because of differences in the adequacy rate without ROSE. Studies with high non-ROSE adequacy rates showed low improvement after ROSE was implemented. Studies must account for the effect of the non-ROSE adequacy rate to determine the effect of ROSE on FNA adequacy rates.
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Tracking donor RBC survival in premature infants: agreement of multiple populations of biotin-labeled RBCs with Kidd antigen-mismatched RBCs.
Pediatr. Res.
PUBLISHED: 02-21-2013
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Background:Anemia, a common condition among critically ill premature infants, is affected by red blood cell (RBC) survival (RCS). We hypothesized that transfused allogeneic Kidd antigen-mismatched RBCs would demonstrate the same concurrent RCS tracking as RBCs multilabeled at separate, discrete low densities with biotin (BioRBCs).Methods:Allogeneic RBCs from adult donors were labeled at four biotin densities, mixed, and transfused into 17 anemic premature infants. Nine of the donors and neonates were Kidd antigen mismatched. Serial posttransfusion blood samples were assayed for up to 8?wk by flow cytometry to track the survival of the proportions of Kidd antigen-mismatched and Kidd antigen-biotinylated RBCs.Results:Using linear mixed modeling to compare results, RCS of the three lowest BioRBC densities was similar to RCS by Kidd antigen mismatch and to one another. RCS of RBCs labeled at the highest BioRBC density was shortened.Conclusion:RCS of different populations of RBCs can be tracked concurrently and reliably using the three lowest BioRBC densities. Although comparable RCS results can be achieved using Kidd antigen mismatches, BioRBCs are preferred for investigating neonatal anemia because biotin labeling of both allogeneic and autologous RBCs is possible.
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Comparison of multiple red cell volume methods performed concurrently in premature infants following allogeneic transfusion.
Pediatr. Res.
PUBLISHED: 02-05-2013
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Study of the pathophysiology and treatment of anemia of prematurity is facilitated by direct measurement of red cell volume (RCV) utilizing microliter quantities of blood samples. Our objective was to compare concurrent measurements of multiple direct RCV methods in infants.
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Significance of atypia in pancreatic and bile duct brushings: Follow-Up analysis of the categories atypical and suspicious for malignancy.
Diagn. Cytopathol.
PUBLISHED: 01-16-2013
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Brushing cytology is frequently utilized for the investigation of pancreatic and biliary strictures but is associated with low diagnostic sensitivity. The Papanicolaou Society of Cytopathology has presented a system for diagnostic classification which includes the categories benign, atypical, suspicious for malignancy and malignant. We studied a series of 216 pancreatic and biliary brushings with either histologic follow-up or a minimum of 6 months clinical follow-up to determine outcomes for the diagnostic categories ("benign," "atypical, favor reactive," "atypical, not otherwise specified," "atypical, suspicious" and "malignant"). Eighty-six of the 216 (39.8%) were designated "atypical" with 10 of these designated as "atypical favor reactive." Forty-five were called "atypical not otherwise specified" and 31 were interpreted as "atypical suspicious for malignancy." On follow-up, 2 of 10 (20%) "atypical favor reactive" were eventually associated with a malignant diagnosis and 23 of 31 (74.2%) "atypical, suspicious for malignancy" demonstrated a malignant outcome. The remaining 45 brushings in the "atypical" category were "atypical not otherwise specified," and 62% of these were associated with malignancy on follow-up. Stratification of the "atypical" category into "atypical favor reactive," "atypical, not otherwise specified" and "atypical, suspicious for malignancy" improves diagnostic accuracy. The "atypical suspicious for malignancy" category has a follow-up similar to the "malignant" category while the "atypical favor reactive" category is associated with a clinical outcome similar to that of the "benign" category. Diagn. Cytopathol. © 2013 Wiley Periodicals, Inc.
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A quantitative study of ?-synuclein pathology in fifteen cases of dementia associated with Parkinson disease.
J Neural Transm
PUBLISHED: 01-09-2013
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The ?-synuclein-immunoreactive pathology of dementia associated with Parkinson disease (DPD) comprises Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG). The densities of LB, LN, LG together with vacuoles, neurons, abnormally enlarged neurons (EN), and glial cell nuclei were measured in fifteen cases of DPD. Densities of LN and LG were up to 19 and 70 times those of LB, respectively, depending on region. Densities were significantly greater in amygdala, entorhinal cortex (EC), and sectors CA2/CA3 of the hippocampus, whereas middle frontal gyrus, sector CA1, and dentate gyrus were least affected. Low densities of vacuoles and EN were recorded in most regions. There were differences in the numerical density of neurons between regions, but no statistical difference between patients and controls. In the cortex, the density of LB and vacuoles was similar in upper and lower laminae, while the densities of LN and LG were greater in upper cortex. The densities of LB, LN, and LG were positively correlated. Principal components analysis suggested that DPD cases were heterogeneous with pathology primarily affecting either hippocampus or cortex. The data suggest in DPD: (1) ratio of LN and LG to LB varies between regions, (2) low densities of vacuoles and EN are present in most brain regions, (3) degeneration occurs across cortical laminae, upper laminae being particularly affected, (4) LB, LN and LG may represent degeneration of the same neurons, and (5) disease heterogeneity may result from variation in anatomical pathway affected by cell-to-cell transfer of ?-synuclein.
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Decision support for hospital bed management using adaptable individual length of stay estimations and shared resources.
BMC Med Inform Decis Mak
PUBLISHED: 01-04-2013
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Elective patient admission and assignment planning is an important task of the strategic and operational management of a hospital and early on became a central topic of clinical operations research. The management of hospital beds is an important subtask. Various approaches have been proposed, involving the computation of efficient assignments with regard to the patients condition, the necessity of the treatment, and the patients preferences. However, these approaches are mostly based on static, unadaptable estimates of the length of stay and, thus, do not take into account the uncertainty of the patients recovery. Furthermore, the effect of aggregated bed capacities have not been investigated in this context. Computer supported bed management, combining an adaptable length of stay estimation with the treatment of shared resources (aggregated bed capacities) has not yet been sufficiently investigated. The aim of our work is: 1) to define a cost function for patient admission taking into account adaptable length of stay estimations and aggregated resources, 2) to define a mathematical program formally modeling the assignment problem and an architecture for decision support, 3) to investigate four algorithmic methodologies addressing the assignment problem and one base-line approach, and 4) to evaluate these methodologies w.r.t. cost outcome, performance, and dismissal ratio.
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Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.
Vet Clin North Am Exot Anim Pract
PUBLISHED: 12-03-2011
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Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.
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A systematic review and meta-analysis of the diagnostic accuracy of frozen section for parotid gland lesions.
Am. J. Clin. Pathol.
PUBLISHED: 10-28-2011
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We conducted a systematic literature review using MEDLINE and Embase to identify articles on diagnostic accuracy of frozen section (FS) for salivary gland lesions published between January 1, 1985, and December 31, 2010. We also reviewed the reference lists of all identified articles and conducted a forward search using Scopus to identify all articles citing the reference set. Meta-analysis was used to produce a summary receiver operating characteristic (SROC) curve from which summary estimates of sensitivity and specificity were obtained. Study quality was assessed using the Quality of Diagnostic Accuracy Study (QUADAS) survey. The accuracy of FS was compared with that of fine-needle aspiration cytology using results from an earlier review. A set of 13 studies (1,880 cases) with extractable data met our inclusion criteria. The summary estimates for the area under the SROC curve, FS sensitivity, and FS specificity are 0.99 (95% confidence interval [CI], 0.98-1.00), 0.90 (95% CI, 0.81-0.94), and 0.99 (95% CI, 0.98-1.00), respectively. FS has acceptable accuracy (90% sensitivity, 99% specificity) and is consistently accurate across study centers.
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Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-26-2011
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The formation of myelin by Schwann cells (SCs) occurs via a series of orchestrated molecular events. We previously used global expression profiling to examine peripheral nerve myelination and identified the NAD(+)-dependent deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in myelination. Here, we show that Sirt2 expression in SCs is correlated with that of structural myelin components during both developmental myelination and remyelination after nerve injury. Transgenic mice lacking or overexpressing Sirt2 specifically in SCs show delays in myelin formation. In SCs, we found that Sirt2 deacetylates Par-3, a master regulator of cell polarity. The deacetylation of Par-3 by Sirt2 decreases the activity of the polarity complex signaling component aPKC, thereby regulating myelin formation. These results demonstrate that Sirt2 controls an essential polarity pathway in SCs during myelin assembly and provide insights into the association between intracellular metabolism and SC plasticity.
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Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure.
J. Lipid Res.
PUBLISHED: 09-25-2011
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Cholesteryl ester transfer protein (CETP) catalyses the exchange of cholesteryl ester and triglyceride between HDL and apoB containing lipoprotein particles. The role of CETP in modulating plasma HDL cholesterol levels in humans is well established and there have been significant efforts to develop CETP inhibitors to increase HDL cholesterol for the treatment of coronary artery disease. These efforts, however, have been hampered by the fact that most CETP inhibitors either have low potency or have undesirable side effects. In this study, we describe a novel benzazepine compound evacetrapib (LY2484595), which is a potent and selective inhibitor of CETP both in vitro and in vivo. Evacetrapib inhibited human recombinant CETP protein (5.5 nM IC(50)) and CETP activity in human plasma (36 nM IC(50)) in vitro. In double transgenic mice expressing human CETP and apoAI, evacetrapib exhibited an ex vivo CETP inhibition ED(50) of less than 5 mg/kg at 8 h post oral dose and significantly elevated HDL cholesterol. Importantly, no blood pressure elevation was observed in rats dosed with evacetrapib at high exposure multiples compared with the positive control, torcetrapib. In addition, in a human adrenal cortical carcinoma cell line (H295R cells), evacetrapib did not induce aldosterone or cortisol biosynthesis whereas torcetrapib dramatically induced aldosterone and cortisol biosynthesis. Our data indicate that evacetrapib is a potent and selective CETP inhibitor without torcetrapib-like off-target liabilities. Evacetrapib is currently in phase II clinical development.
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Fiber-coupled displacement interferometry without periodic nonlinearity.
Opt Lett
PUBLISHED: 09-21-2011
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Displacement interferometry is widely used for accurately characterizing nanometer and subnanometer displacements in many applications. In many modern systems, fiber delivery is desired to limit optical alignment and remove heat sources from the system, but fiber delivery can exacerbate common interferometric measurement problems, such as periodic nonlinearity, and account for fiber-induced drift. In this Letter, we describe a novel, general Joo-type interferometer that inherently has an optical reference after any fiber delivery that eliminates fiber-induced drift. This interferometer demonstrated no detectable periodic nonlinearity in both free-space and fiber-delivered variants.
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A systematic review and meta-analysis of the diagnostic accuracy of ultrasound-guided core needle biopsy for salivary gland lesions.
Am. J. Clin. Pathol.
PUBLISHED: 09-16-2011
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Core needle biopsy (CNB) of salivary gland lesions is a relatively new technique that may offer benefits for diagnosis of the lesions. We conducted a systematic literature review to identify studies published between January 1, 1985, and March 15, 2011. Summary estimates of sensitivity and specificity were obtained by using a summary receiver-operating characteristic (SROC) curve. Study quality was assessed by using the QUADAS survey. We identified 5 studies (277 cases) for inclusion. The area under the SROC for CNB was 1.00 (95% confidence interval [CI], 0.99-1.00). Based on histologically verified cases, the sensitivity of CNB is 0.92 (95% CI, 0.77-0.98) and the specificity is 1.00 (95% CI, 0.76-1.00). We conclude that CNB has high accuracy and a low (1.2%) inadequacy rate. CNB is more accurate than fine-needle aspiration, at least in some settings, but the best selection of which test to use for an individual patient and setting remains to be defined.
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grassy tillers1 promotes apical dominance in maize and responds to shade signals in the grasses.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-01-2011
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The shape of a plant is largely determined by regulation of lateral branching. Branching architecture can vary widely in response to both genotype and environment, suggesting regulation by a complex interaction of autonomous genetic factors and external signals. Tillers, branches initiated at the base of grass plants, are suppressed in response to shade conditions. This suppression of tiller and lateral branch growth is an important trait selected by early agriculturalists during maize domestication and crop improvement. To understand how plants integrate external environmental cues with endogenous signals to control their architecture, we have begun a functional characterization of the maize mutant grassy tillers1 (gt1). We isolated the gt1 gene using positional cloning and found that it encodes a class I homeodomain leucine zipper gene that promotes lateral bud dormancy and suppresses elongation of lateral ear branches. The gt1 expression is induced by shading and is dependent on the activity of teosinte branched1 (tb1), a major domestication locus controlling tillering and lateral branching. Interestingly, like tb1, gt1 maps to a quantitative trait locus that regulates tillering and lateral branching in maize and shows evidence of selection during maize domestication. Branching and shade avoidance are both of critical agronomic importance, but little is known about how these processes are integrated. Our results indicate that gt1 mediates the reduced branching associated with the shade avoidance response in the grasses. Furthermore, selection at the gt1 locus suggests that it was involved in improving plant architecture during the domestication of maize.
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Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function.
J. Neurosci.
PUBLISHED: 07-15-2011
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Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here, we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable, but as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies.
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A systematic review and meta-analysis of the diagnostic accuracy of fine-needle aspiration cytology for parotid gland lesions.
Am. J. Clin. Pathol.
PUBLISHED: 06-21-2011
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The clinical usefulness of fine-needle aspiration cytology (FNAC) for the diagnosis of parotid gland lesions is controversial. Many accuracy studies have been published, but the literature has not been adequately summarized. We identified 64 studies on the diagnosis of malignancy (6,169 cases) and 7 studies on the diagnosis of neoplasia (795 cases). The diagnosis of neoplasia (area under the summary receiver operating characteristic [AUSROC] curve, 0.99; 95% confidence interval [CI], 0.97-1.00) had higher accuracy than the diagnosis of malignancy (AUSROC, 0.96; 95% CI, 0.94-0.97). Several sources of bias were identified that could affect study estimates. Studies on the diagnosis of malignancy showed significant heterogeneity (P < .001). The subgroups of American, French, and Turkish studies showed greater homogeneity, but the accuracy of these subgroups was not significantly different from that of the remaining subgroup. It is not possible to provide a general guideline on the clinical usefulness of FNAC for parotid gland lesions owing to the variability in study results. There is a need to improve the quality of reporting and to improve study designs to remove or assess the impact of bias.
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Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis.
Arch. Neurol.
PUBLISHED: 05-09-2011
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To describe the development of progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA) treated with rituximab.
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BARREN STALK FASTIGIATE1 is an AT-hook protein required for the formation of maize ears.
Plant Cell
PUBLISHED: 05-03-2011
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Ears are the seed-bearing inflorescences of maize (Zea mays) plants and represent a crucial component of maize yield. The first step in the formation of ears is the initiation of axillary meristems in the axils of developing leaves. In the classic maize mutant barren stalk fastigiate1 (baf1), first discovered in the 1950s, ears either do not form or, if they do, are partially fused to the main stalk. We positionally cloned Baf1 and found that it encodes a transcriptional regulator containing an AT-hook DNA binding motif. Single coorthologs of Baf1 are found in syntenic regions of brachypodium (Brachypodium distachyon), rice (Oryza sativa), and sorghum (Sorghum bicolor), suggesting that the gene is likely present in all cereal species. Protein-protein interaction assays suggest that BAF1 is capable of forming homodimers and heterodimers with other members of the AT-hook family. Another transcriptional regulator required for ear initiation is the basic helix-loop-helix protein BARREN STALK1 (BA1). Genetic and expression analyses suggest that Baf1 is required to reach a threshold level of Ba1 expression for the initiation of maize ears. We propose that Baf1 functions in the demarcation of a boundary region essential for the specification of a stem cell niche.
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Structural and pH dependence of excited state PCET reactions involving reductive quenching of the MLCT excited state of [RuII(bpy)2(bpz)]2+ by hydroquinones.
J Phys Chem A
PUBLISHED: 03-24-2011
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The proton-coupled electron transfer (PCET) reaction between the bpz-based photoexcited (3)MLCT state of [Ru(II)(bpy)(2)(bpz)](2+) (bpy = 2,2-bipyridine, bpz = 2,2-bipyrazine) and a series of substituted hydroquinones (H(2)Q) has been studied by transient absorption (TA) and time-resolved electron paramagnetic resonance (TREPR) spectroscopy at X-band. When the reaction is carried out in a CH(3)CN/H(2)O mixed solvent system with unsubstituted hydroquinone, the neutral semiquinone radical (4a) and its conjugate base, the semiquinone radical anion (4b), are both observed. Variation of the acid strength in the solvent mixture allows the acid/base dependence of the PCET reaction to be investigated. In solutions with very low acid concentrations, TREPR spectra exclusively derived from radical anion 4b are observed, while at very high acid concentrations, the spectrum is assigned to the protonated structure 4a. At intermediate acid concentrations, either a superposition of spectra is observed (slow exchange between 4a and 4b) or substantial broadening in the TREPR spectrum is observed (fast exchange between 4a and 4b). Variation of substituents on the H(2)Q ring substantially alter this acid/base dependence and provide a means to investigate electronic effects on both the ET and PT components of the PCET process. The TA results suggest a change in mechanism from PCET to direct ET quenching in strongly basic solutions and with electron withdrawing groups on the H(2)Q ring system. Changing the ligand on the Ru complex also alters the acid/base dependence of the TREPR spectra through a series of complex equilibria between protonated and deprotonated hydroquinone radicals and anions. The relative intensities of the signals from radical 4a versus 4b can be rationalized quantitatively in terms of these equilibria and the relevant pK(a) values. An observed equilibrium deuterium isotope effect supports the conclusion that the post-PCET HQ(•)/Q(•-) equilibrium is the most important in determining the 4a/4b ratio at early delay times.
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Differential pharmacokinetic analysis of in vivo erythropoietin receptor interaction with erythropoietin and continuous erythropoietin receptor activator in sheep.
Biopharm Drug Dispos
PUBLISHED: 03-04-2011
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The two erythropoiesis stimulating agents (ESAs), short acting recombinant human erythropoietin (EPO) and long acting continuous erythropoietin receptor activator (CERA), have been hypothesized to share an in vivo elimination pathway that involves binding to erythropoietin receptor (EPOR) and subsequent internalization. A physiologically based recirculation model and a pharmacokinetic tracer interaction methodology (TIM) were used to compare the in vivo interaction kinetics with EPOR between the two ESAs in adult sheep. Animals treated with EPO experienced a greater EPOR up-regulation than those treated with CERA, as evidenced by an eightfold-higher initial EPOR normalized production rate constant, k(syn) /R(0) , versus a twofold-larger EPOR degradation rate constant, k(deg) . In agreement with in vitro studies, EPO had a lower in vivo equilibrium dissociation constant from EPOR than CERA (K(D) = 6 versus 88.4 pmol/l, respectively, p < 0.01). The internalization and/or degradation of the EPO-EPOR complex was faster than that of the CERA-EPOR complex (k(int) = 24 versus 2.41 h(-1) , respectively, p < 0.01). The adopted model enables a mechanism-based explanation for CERAs slower elimination and greater erythropoietic activity in vivo. As predicted by the model, the slower elimination of CERA is due to: (1) less EPOR up-regulation induced by CERA administration; (2) slower binding of CERA to EPOR; and (3) reduced internalization and/or degradation rate of surface-bound CERA. Slower CERA/EPOR complex elimination explains the greater in vivo erythropoiesis reported for CERA, despite its lower affinity to EPOR. A sensitivity analysis showed that the model parameters were reliably estimated using the TIM methodology.
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Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia.
Exp. Neurol.
PUBLISHED: 02-28-2011
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The Akita mouse is a robust model of diabetic autonomic neuropathy which develops severe diabetes following beta cell death, which occurs reproducibly at 3-4 weeks of age, and maintains the diabetic state without therapy for as long as 11 additional months. Neuritic dystrophy and neuronopathy involving prevertebral sympathetic superior mesenteric and celiac ganglia begin to develop within the first two months of onset of diabetes and are progressive with time. We have examined the effect of insulin implants resulting in normoglycemia and injections of ARA290, a small erythropoietin peptide which has no effect on glycemic parameters, on the reversal of established neuritic dystrophy and neuronopathy. We have found that 4 weeks of insulin therapy beginning at 2 months of diabetes resulted in normalization of blood glucose, body weight and HbA1c. Insulin therapy successfully reversed established neuritic dystrophy and neuronopathy to control levels. Numbers of sympathetic neurons were not significantly changed in either 3 month diabetic or insulin-treated Akita mice. Treatment with ARA290 for 7 weeks beginning at 4 months of diabetes did not result in altered metabolic severity of diabetes as measured by blood glucose, body weight or HbA1c levels. ARA290 treatment was able to decrease neuritic dystrophy by 55-74% compared to untreated diabetics or in comparison to a separate group of diabetic animals representing the 4 month treatment onset point. Surprisingly, there was no effect of ARA290 on ganglionic neuron number or ongoing neuronopathy (pale/degenerating neurons) in diabetic Akita mice during this time period. The development of neuroprotective EPO-like peptides may provide a possible future therapy for this debilitating complication of diabetes; however, it appears that discrete elements may be differentially targeted by the diabetic state and may require selective therapy.
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Fast, ligand- and solvent-free synthesis of 1,4-substituted buta-1,3-diynes by Cu-catalyzed homocoupling of terminal alkynes in a ball mill.
Chemistry
PUBLISHED: 02-24-2011
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A method for the Glaser coupling reaction of alkynes by using a vibration ball mill has been developed. The procedure avoids the use of ligands and solvents during the reaction. Aryl- and alkyl-substituted terminal alkynes undergo homocoupling if coground with KF-Al(2)O(3) and CuI as a milling auxiliary and catalyst. Furthermore, an alternative protocol has been developed incorporating 1,4-diazabicyclo[2.2.2]octane (DABCO) as an additional base allowing the use of KF-Al(2)O(3) with a lower KF loading. Besides Cu salts, the homocoupling of phenylacetylene is also catalyzed by Ni or Co salts, as well as by PdCl(2). TMS-protected phenylacetylene could be directly converted into the homocoupling product after in situ deprotection of the alkyne by fluoride-initiated removal of the trimethylsilyl group.
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Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.
Pain
PUBLISHED: 01-24-2011
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Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects.
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Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-11-2011
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Novel chroman and tetrahydroquinoline ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that aryl substituents on the 7- or 8-position of both bicyclic scaffolds imparted the best in vitro potency at TRPV1. The most potent chroman ureas were assessed in chronic and acute pain models, and compounds with the ability to cross the blood-brain barrier were shown to be highly efficacious. The tetrahydroquinoline ureas were found to be potent CYP3A4 inhibitors, but replacement of bulky substituents at the nitrogen atom of the tetrahydroisoquinoline moiety with small groups such as methyl can minimize the inhibition.
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Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords.
Neuroimage
PUBLISHED: 01-05-2011
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Correlation of diffusion tensor imaging (DTI) with histochemical staining for demyelination and axonal damage in multiple sclerosis (MS) ex vivo human cervical spinal cords.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.