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Find video protocols related to scientific articles indexed in Pubmed.
Reporter-based Growth Assay for Systematic Analysis of Protein Degradation.
J Vis Exp
PUBLISHED: 11-20-2014
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Protein degradation by the ubiquitin-proteasome system (UPS) is a major regulatory mechanism for protein homeostasis in all eukaryotes. The standard approach to determining intracellular protein degradation relies on biochemical assays for following the kinetics of protein decline. Such methods are often laborious and time consuming and therefore not amenable to experiments aimed at assessing multiple substrates and degradation conditions. As an alternative, cell growth-based assays have been developed, that are, in their conventional format, end-point assays that cannot quantitatively determine relative changes in protein levels. Here we describe a method that faithfully determines changes in protein degradation rates by coupling them to yeast cell-growth kinetics. The method is based on an established selection system where uracil auxotrophy of URA3-deleted yeast cells is rescued by an exogenously expressed reporter protein, comprised of a fusion between the essential URA3 gene and a degradation determinant (degron). The reporter protein is designed so that its synthesis rate is constant whilst its degradation rate is determined by the degron. As cell growth in uracil-deficient medium is proportional to the relative levels of Ura3, growth kinetics are entirely dependent on the reporter protein degradation. This method accurately measures changes in intracellular protein degradation kinetics. It was applied to: (a) Assessing the relative contribution of known ubiquitin-conjugating factors to proteolysis (b) E2 conjugating enzyme structure-function analyses (c) Identification and characterization of novel degrons. Application of the degron-URA3-based system transcends the protein degradation field, as it can also be adapted to monitoring changes of protein levels associated with functions of other cellular pathways.
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Country of birth does not influence long-term clinical, virological and immunological outcome of HIV-infected children living in the Netherlands: a cohort study comparing children born in the Netherlands to children born in sub-Saharan Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 11-19-2014
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Immigrant HIV-infected adults in industrialized countries show a poorer clinical and virological outcome compared to native patients. We aimed to investigate potential differences in clinical, immunological and virological outcome in Dutch HIV-infected children born in the Netherlands (NL) versus born in Sub-Saharan Africa (SSA) in a national cohort-analysis.
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Effects of estrogen and venlafaxine on menopause-related quality of life in healthy postmenopausal women with hot flashes: a placebo-controlled randomized trial.
Menopause
PUBLISHED: 11-19-2014
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This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes.
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Observational drawing biases are predicted by biases in perception: Empirical support of the misperception hypothesis of drawing accuracy with respect to two angle illusions.
Q J Exp Psychol (Hove)
PUBLISHED: 11-19-2014
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We tested the misperception hypothesis of drawing errors, which states that drawing accuracy is strongly influenced by the perceptual encoding of a to-be-drawn stimulus. We used a highly controlled experimental paradigm in which nonartist participants made perceptual judgements and drawings of angles under identical stimulus exposure conditions. Experiment 1 examined the isosceles/scalene triangle angle illusion; congruent patterns of bias in the perception and drawing tasks were found for 40 and 60° angles, but not for 20 or 80° angles, providing mixed support for the misperception hypothesis. Experiment 2 examined shape constancy effects with respect to reproductions of single acute or obtuse angles; congruent patterns of bias in the perception and drawing tasks were found across a range of angles from 29 to 151°, providing strong support for the misperception hypothesis. In both experiments, perceptual and drawing biases were positively correlated. These results are largely consistent with the misperception hypothesis, suggesting that inaccurate perceptual encoding of angles is an important reason that nonartists err in drawing angles from observation.
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Glial abnormalities in mood disorders.
Harv Rev Psychiatry
PUBLISHED: 11-08-2014
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Multiple lines of evidence indicate that mood disorders are associated with abnormalities in the brain's cellular composition, especially in glial cells. Considered inert support cells in the past, glial cells are now known to be important for brain function. Treatments for mood disorders enhance glial cell proliferation, and experimental stimulation of cell growth has antidepressant effects in animal models of mood disorders. These findings suggest that the proliferation and survival of glial cells may be important in the pathogenesis of mood disorders and may be possible targets for the development of new treatments. In this article we review the evidence for glial abnormalities in mood disorders, and we discuss glial cell biology and evidence from postmortem studies of mood disorders. The goal is not to carry out a comprehensive review but to selectively discuss existing evidence in support of an argument for the role of glial cells in mood disorders.
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Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network.
Menopause
PUBLISHED: 09-25-2014
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This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials.
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[Management of aortic stenosis in patients undergoing non-cardiac surgery.]
Presse Med
PUBLISHED: 08-20-2014
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There is a significant risk of cardiovascular morbidity and mortality in patients with severe aortic stenosis (valve area < 1 cm(2) or 0.6 cm(2)/m(2) body surface area) undergoing non-cardiac surgery, especially in patients with symptoms (dyspnoea, angina, syncope, or heart failure). Before any surgery, clinical assessment should search for signs of aortic stenosis which justifies echocardiographic examination, particularly in the elderly. A systematic rest echocardiography with searching aortic stenosis should be considered in patients undergoing high risk surgery. The key points of pre-operative cardiac risk assessment are: assessment of the severity of aortic stenosis, measurement of the functional capacity, evaluation of the left ventricular function, search of associated coronary artery disease, estimate of the surgical risk of cardiac events, and achievement of risk indices. In symptomatic patients with severe aortic stenosis, only urgent non-cardiac surgery should be performed under careful haemodynamic monitoring. Aortic valve replacement should be considered before elective non-cardiac surgery. In asymptomatic patients with severe aortic stenosis, aortic valve replacement should be considered before non-cardiac high risk surgery. Non-cardiac surgery at low/intermediate risk can be performed provided an adapted anaesthetic technique.
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Reproducibility of T2 * mapping in the human cerebral cortex in vivo at 7 tesla MRI.
J Magn Reson Imaging
PUBLISHED: 08-19-2014
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To assess the test-retest reproducibility of cortical mapping of T2 * relaxation rates at 7 Tesla (T) MRI. T2 * maps have been used for studying cortical myelo-architecture patterns in vivo and for characterizing conditions associated with changes in iron and/or myelin concentration.
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Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.
J. Thromb. Haemost.
PUBLISHED: 08-14-2014
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Background. Cardiac involvement is a major cause of mortality in thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed due to sub-clinical injuries. Cardiac troponin-I (cTnI) on admission could improve early diagnosis of cardiac involvement and have a prognostic value. Objectives. To assess the predictive value of cTnI-I in TTP for death or refractoriness. Patients/Methods. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS13 deficiency (<10%) and included in the registry of the French reference center for thrombotic microangiopathies. Centralized cTnI measurements were performed from frozen serum on admission. Results. Between January, 2003 and December, 2011, 133 patients with TTP (mean age, 48±17 year-old) had available cTnI measurement on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI (>0.1?g/L) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. Main outcomes were death (25%) and refractoriness (17%). Age (P=0.02) and cTnI level (P=0.002) showed the greatest impact on survival. A cTnI level >0.25 ?g/L was the only independent factor in predicting death (Odds-ratio [OR] 2.87; 95% confidence interval [CI]: 1.13-7.22; P=0.024) and/or refractoriness (OR 3.03; 95%CI: 1.27-7.3; P=0.01). Conclusions. CTnI >0.25 ?g/L at presentation in TTP appears as an independent factor associated with a threefold increase in death risk or refractoriness. Therefore, cTnI levels should be considered as part of prognostic indicator in patients diagnosed with TTP. This article is protected by copyright. All rights reserved.
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Automatic labeling of vertebral levels using a robust template-based approach.
Int J Biomed Imaging
PUBLISHED: 07-15-2014
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Context. MRI of the spinal cord provides a variety of biomarkers sensitive to white matter integrity and neuronal function. Current processing methods are based on manual labeling of vertebral levels, which is time consuming and prone to user bias. Although several methods for automatic labeling have been published; they are not robust towards image contrast or towards susceptibility-related artifacts. Methods. Intervertebral disks are detected from the 3D analysis of the intensity profile along the spine. The robustness of the disk detection is improved by using a template of vertebral distance, which was generated from a training dataset. The developed method has been validated using T1- and T2-weighted contrasts in ten healthy subjects and one patient with spinal cord injury. Results. Accuracy of vertebral labeling was 100%. Mean absolute error was 2.1 ± 1.7?mm for T2-weighted images and 2.3 ± 1.6?mm for T1-weighted images. The vertebrae of the spinal cord injured patient were correctly labeled, despite the presence of artifacts caused by metallic implants. Discussion. We proposed a template-based method for robust labeling of vertebral levels along the whole spinal cord for T1- and T2-weighted contrasts. The method is freely available as part of the spinal cord toolbox.
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MiR-126 Regulates Growth Factor Activities and Vulnerability to Toxic Insult in Neurons.
Mol. Neurobiol.
PUBLISHED: 07-10-2014
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Dysfunction of growth factor (GF) activities contributes to the decline and death of neurons during aging and in neurodegenerative diseases. In addition, neurons become more resistant to GF signaling with age. Micro (mi)RNAs are posttranscriptional regulators of gene expression that may be crucial to age- and disease-related changes in GF functions. MiR-126 is involved in regulating insulin/IGF-1/phosphatidylinositol-3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) signaling, and we recently demonstrated a functional role of miR-126 in dopamine neuronal cell survival in models of Parkinson's disease (PD)-associated toxicity. Here, we show that elevated levels of miR-126 increase neuronal vulnerability to ubiquitous toxicity mediated by staurosporine (STS) or Alzheimer's disease (AD)-associated amyloid beta 1-42 peptides (A?1-42). The neuroprotective factors IGF-1, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and soluble amyloid precursor protein ? (sAPP?) could diminish but not abrogate the toxic effects of miR-126. In miR-126 overexpressing neurons derived from Tg6799 familial AD model mice, we observed an increase in A?1-42 toxicity, but surprisingly, both A?1-42 and miR-126 promoted neurite sprouting. Pathway analysis revealed that miR-126 overexpression downregulated elements in the GF/PI3K/AKT and ERK signaling cascades, including AKT, GSK-3?, ERK, their phosphorylation, and the miR-126 targets IRS-1 and PIK3R2. Finally, inhibition of miR-126 was neuroprotective against both STS and A?1-42 toxicity. Our data provide evidence for a novel mechanism of regulating GF/PI3K signaling in neurons by miR-126 and suggest that miR-126 may be an important mechanistic link between metabolic dysfunction and neurotoxicity in general, during aging, and in the pathogenesis of specific neurological disorders, including PD and AD.
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Omega-3 Fatty acids and gestational length in a high-risk psychiatric population due to psychiatric morbidity and medication exposure during pregnancy.
J Clin Psychopharmacol
PUBLISHED: 07-10-2014
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Premature birth is associated with infant morbidity and mortality. Women with psychiatric disorders represent an at-risk population for premature delivery and other obstetrical complications. The primary aim of this study was to assess the association between omega-3 fatty acid use and length of gestation.
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Recovery of locomotion after partial spinal cord lesions in cats: assessment using behavioral, electrophysiological and imaging techniques.
Acta Neurobiol Exp (Wars)
PUBLISHED: 07-05-2014
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This short review summarizes experimental findings made after spinal cord injury, mainly in cats. After a complete spinal injury, cats re-express hindlimb locomotion after 2-3 weeks because of a spinal locomotor circuitry named the central pattern generator or CPG. To investigate whether such circuits are also implicated in the recovery of locomotion after partial spinal lesions, we have used a dual spinal lesion paradigm. Essentially, after an initial unilateral hemisection, cats spontaneously recover quadrupedal locomotion. When a complete section is then performed 3 weeks after this hemisection, cats can walk with the hindlimbs within 24 hours compared to 2-3 weeks in cats with single complete spinal lesions demonstrating the importance of spinal mechanisms after partial lesions. Using kinematic and electromyographic methods to evaluate the changes throughout the dual lesion paradigm, we could show that the spinal cord reorganizes spontaneously without locomotor training or with training provided between the partial and complete spinal lesion. To assess spinal lesions we have used histology and magnetic resonance imaging (MRI). We will describe some advanced MRI techniques such as diffusion and magnetization transfer, which provide higher specificity to axon degeneration and demyelination. Examples of advanced MRI techniques in cats and humans are described, including the current limitations and perspectives.
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Three-dimensional transesophageal echocardiography for descending aortic atheroma: a preliminary study.
Int J Cardiovasc Imaging
PUBLISHED: 06-22-2014
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Transesophageal echocardiography (TEE) is an efficient method for characterization of aortic atherosclerotic plaques (AAP). The aim of our study was to evaluate the feasibility and the additional contribution of three-dimensional (3D) TEE in the evaluation of AAPs in descending thoracic aorta. We studied 82 patients referred for TEE regardless of the indication. All patients underwent two-dimensional (2D) conventional acquisitions. A 3D TEE study was performed for all AAPs localized in the descending thoracic aorta. Thickness, degree of calcification, the presence of ulceration or mobile debris were compared for 2D and 3D modes. From 3D data, three types of AAPs were defined according to their morphological characteristics (surface and contours). Among 192 AAPs found on 2D acquisition, 189 (98.4 %) were also identified by 3D TEE. For AAP characterization, agreement was good between 2D TEE and 2D extracted from 3D with the multiplanar reconstruction mode: 83.6 % (k = 0.69) for thickness and 82.5 % (k = 0.72) for degree of calcification. All AAPs ulcerations (n = 13) and mobile debris (n = 3) seen in 2D were identified in 3D. 2D characteristics of the 3D AAPs' morphological types were different: type I plaques were thin and rarely calcified; type III plaques were thicker and often calcified; and type II presented intermediate characteristics. There was overlap among groups and the 3D morphology could not be predicted from 2D data. 3D TEE is a feasible method for the analysis of AAPs. In addition to conventional characterization, 3D TEE provides a new morphological approach to AAPs.
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Antidepressant use in pregnancy and the risk of cardiac defects.
N. Engl. J. Med.
PUBLISHED: 06-19-2014
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Whether the use of selective serotonin-reuptake inhibitors (SSRIs) and other antidepressants during pregnancy is associated with an increased risk of congenital cardiac defects is uncertain. In particular, there are concerns about a possible association between paroxetine use and right ventricular outflow tract obstruction and between sertraline use and ventricular septal defects.
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Discontinuation of antidepressants during attempts to conceive: a pilot trial of cognitive behavioral therapy for the prevention of recurrent depression.
J Clin Psychopharmacol
PUBLISHED: 06-10-2014
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Many women discontinue antidepressants (ADs) when trying to conceive, although risk of depressive relapse is high. We examined the feasibility and potential clinical effect of cognitive behavioral therapy for the prevention of recurrence (CBT-PR) for women with a history of recurrent major depressive disorder (MDD) who planned to discontinue maintenance AD treatment for pregnancy.
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Unlimited capacity parallel quantity comparison of multiple integers.
J Exp Psychol Learn Mem Cogn
PUBLISHED: 05-12-2014
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Research has shown that integer comparison is quick and efficient. This efficiency may be a function of the structure of the integer comparison system. The present study tests whether integers are compared with an unlimited capacity system or a limited capacity system. We tested these models using a visual search task with time delimitation. The data from Experiments 1 and 2 indicate that integers are encoded, identified, and compared within an unlimited capacity system. The data from Experiment 3 indicate that 2nd-order magnitude comparisons are processed with a highly efficient limited capacity system.
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Prevalence of atypical antipsychotic use in psychiatric outpatients: comparison of women of childbearing age with men.
Arch Womens Ment Health
PUBLISHED: 05-07-2014
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To characterize current treatment practices, we compared the use of atypical antipsychotic drugs among women of childbearing age to men based on electronic medical records of 1073 hospital-based psychiatric outpatients given at least one second-generation antipsychotic drug. One quarter of psychiatric outpatients sampled were prescribed at least one atypical antipsychotic, in more than half of cases for off-label indications. Women were significantly more likely than men to be diagnosed with mood or anxiety disorders than psychotic disorders and to be prescribed quetiapine (60.7 vs. 48.0 %) or aripiprazole (31.2 vs. 23.9 %), but less likely risperidone (15.8 vs. 26.1 %) or ziprasidone (10 vs. 14 %).
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Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 04-23-2014
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We have recently reported the creation and initial characterization of an etiology-based recombinant mouse model of a severe and inherited form of Major Depressive Disorder (MDD). This was achieved by replacing the corresponding mouse DNA sequence with a 6-base DNA sequence from the human CREB1 promoter that is associated with MDD in individuals from families with recurrent, early-onset MDD (RE-MDD). In the current study, we explored the effect of the pathogenic Creb1 allele on gene expression in the mouse hippocampus, a brain region that is altered in structure and function in MDD. Mouse whole-genome profiling was performed using the Illumina MouseWG-6 v2.0 Expression BeadChip microarray. Univariate analysis identified 269 differentially-expressed genes in the hippocampus of the mutant mouse. Pathway analyses highlighted 11 KEGG pathways: the phosphatidylinositol signaling system, which has been widely implicated in MDD, Bipolar Disorder, and the action of mood stabilizers; gap junction and long-term potentiation, which mediate cognition and memory functions often impaired in MDD; cardiac muscle contraction, insulin signaling pathway, and three neurodegenerative brain disorders (Alzheimer's, Parkinson's, and Huntington's Diseases) that are associated with MDD; ribosome and proteasome pathways affecting protein synthesis/degradation; and the oxidative phosphorylation pathway that is key to energy production. These findings illustrate the merit of this congenic C57BL/6 recombinant mouse as a model of RE-MDD, and demonstrate its potential for highlighting molecular and cellular pathways that contribute to the biology of MDD. The results also inform our understanding of the mechanisms that underlie the comorbidity of MDD with other disorders.
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Acute and long-term behavioral outcome of infants and children exposed in utero to either maternal depression or antidepressants: a review of the literature.
J Clin Psychiatry
PUBLISHED: 04-10-2014
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The authors reviewed the published literature on the acute and long-term neurobehavioral effects on infants and children of either in utero exposure to maternal depression or in utero exposure to antidepressants.
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Exploring the role of central astrocytic glutamate uptake in ethanol reward in mice.
Alcohol. Clin. Exp. Res.
PUBLISHED: 03-21-2014
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Alcoholism is associated with specific brain abnormalities revealed through postmortem studies, including a reduction in glial cell number and dysregulated glutamatergic neurotransmission. Whether these abnormalities contribute to the etiology of alcoholism, are consequences of alcohol use, or both is still unknown.
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Robust, accurate and fast automatic segmentation of the spinal cord.
Neuroimage
PUBLISHED: 03-10-2014
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Spinal cord segmentation provides measures of atrophy and facilitates group analysis via inter-subject correspondence. Automatizing this procedure enables studies with large throughput and minimizes user bias. Although several automatic segmentation methods exist, they are often restricted in terms of image contrast and field-of-view. This paper presents a new automatic segmentation method (PropSeg) optimized for robustness, accuracy and speed. The algorithm is based on the propagation of a deformable model and is divided into three parts: firstly, an initialization step detects the spinal cord position and orientation using a circular Hough transform on multiple axial slices rostral and caudal to the starting plane and builds an initial elliptical tubular mesh. Secondly, a low-resolution deformable model is propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a local contrast-to-noise adaptation at each iteration. Thirdly, a refinement process and a global deformation are applied on the propagated mesh to provide an accurate segmentation of the spinal cord. Validation was performed in 15 healthy subjects and two patients with spinal cord injury, using T1- and T2-weighted images of the entire spinal cord and on multiecho T2*-weighted images. Our method was compared against manual segmentation and against an active surface method. Results show high precision for all the MR sequences. Dice coefficients were 0.9 for the T1- and T2-weighted cohorts and 0.86 for the T2*-weighted images. The proposed method runs in less than 1min on a normal computer and can be used to quantify morphological features such as cross-sectional area along the whole spinal cord.
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In vivo evidence for cerebral bioenergetic abnormalities in schizophrenia measured using 31P magnetization transfer spectroscopy.
JAMA Psychiatry
PUBLISHED: 03-04-2014
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Abnormalities in neural activity and cerebral bioenergetics have been observed in schizophrenia (SZ). Further defining energy metabolism anomalies would provide crucial information about molecular mechanisms underlying SZ and may be valuable for developing novel treatment strategies.
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Noise genetics: inferring protein function by correlating phenotype with protein levels and localization in individual human cells.
PLoS Genet.
PUBLISHED: 03-01-2014
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To understand gene function, genetic analysis uses large perturbations such as gene deletion, knockdown or over-expression. Large perturbations have drawbacks: they move the cell far from its normal working point, and can thus be masked by off-target effects or compensation by other genes. Here, we offer a complementary approach, called noise genetics. We use natural cell-cell variations in protein level and localization, and correlate them to the natural variations of the phenotype of the same cells. Observing these variations is made possible by recent advances in dynamic proteomics that allow measuring proteins over time in individual living cells. Using motility of human cancer cells as a model system, and time-lapse microscopy on 566 fluorescently tagged proteins, we found 74 candidate motility genes whose level or localization strongly correlate with motility in individual cells. We recovered 30 known motility genes, and validated several novel ones by mild knockdown experiments. Noise genetics can complement standard genetics for a variety of phenotypes.
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Transient receptor potential melastatin (TRPM) channels mediate clozapine-induced phenotypes in Caenorhabditis elegans.
J. Neurogenet.
PUBLISHED: 02-25-2014
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The molecular mechanisms of action of antipsychotic drugs (APDs) are not fully understood. Here, we characterize phenotypes of missense and knockout mutations in the Caenorhabditis elegans transient receptor potential melastatin (TRPM) channel ortholog gtl-2, a candidate APD target identified in a genome-wide RNAi (RNA interference) screen for Suppressors of Clozapine-induced Larval Arrest (scla genes). We then employ the developmental phenotypes of gtl-2(lf) mutants to validate our previous gtl-2(RNAi) result. GTL-2 acts in the excretory canal cell to regulate Mg(2+) homeostasis. Using exc (excretory canal abnormal) gene mutants, we demonstrate that excretory canal cell function is necessary for clozapine-induced developmental delay and lethality. Moreover, cell-specific promoter-driven expression studies reveal that GTL-2 function in the excretory canal cell is important for its role in the SCLA phenotype. We then investigate the mechanism by which GTL-2 function in the excretory canal cell impacts clozapine-induced phenotypes. gtl-2(lf) mutations cause hypermagnesemia, and we show that exposure of the wild-type strain to high Mg(2+) phenocopies gtl-2(lf) with respect to suppression of clozapine-induced developmental delay and lethality. Our results suggest that GTL-2 TRPM channel function in the excretory canal cell is important for clozapine's developmental effects. TRP channels are expressed in mammalian brain and are implicated in the pathogenesis of mental illnesses but have not been previously implicated in APD action.
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The Human Ortholog of Acid-Sensing Ion Channel Gene ASIC1a Is Associated with Panic Disorder and Amygdala Structure and Function.
Biol. Psychiatry
PUBLISHED: 02-18-2014
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Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide, possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that carbon dioxide-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid-sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function.
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Developing an exchange strategy.
Healthc Financ Manage
PUBLISHED: 02-12-2014
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Developing a health insurance exchange strategy begins with: Understanding how both the public and private exchanges work. Conducting a thorough analysis to quantify how exchanges will affect the organization's current and future patient populations and revenue base. Determining when to participate in the exchanges, keeping in mind current market position as well as competitors' actions.
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S.E. Mitchell Vascular Anomalies Flow Chart (SEMVAFC): a visual pathway combining clinical and imaging findings for classification of soft-tissue vascular anomalies.
Clin Radiol
PUBLISHED: 02-11-2014
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Classification of vascular anomalies (VAs) is challenging due to overlapping clinical symptoms, confusing terminology in the literature and unfamiliarity with this complex entity. It is important to recognize that VAs include two distinct entities, vascular tumours (VTs) and vascular malformations (VaMs). In this article, we describe SE Mitchell Vascular Anomalies Flow Chart (SEMVAFC), which arises from a multidisciplinary approach that incorporates clinical symptoms, physical examination and magnetic resonance imaging (MRI) findings to establish International Society for the Study of Vascular Anomalies (ISSVA)-based classification of the VAs. SEMVAFC provides a clear visual pathway for physicians to accurately diagnose Vas, which is important as treatment, management, and prognosis differ between VTs and VaMs.
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Children's number-line estimation shows development of measurement skills (not number representations).
Dev Psychol
PUBLISHED: 02-10-2014
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Children's understanding of numbers is often assessed using a number-line task, where the child is shown a line labeled with 0 at one end and a higher number (e.g., 100) at the other end. The child is then asked where on the line some intermediate number (e.g., 70) should go. Performance on this task changes predictably during childhood, and this has often been interpreted as evidence of a change in the child's psychological representation of integer quantities. The present article presents theoretical and empirical evidence that the change in number-line performance actually reflects the development of measurement skills used in the task. We compare 2 versions of the number-line task: the bounded version used in the literature and a new, unbounded version. Results indicate that it is only children's performance on the bounded task (which requires subtraction or division) that changes markedly with age. In contrast, children's performance on the unbounded task (which requires only addition) remains fairly constant as they get older. Thus, developmental changes in performance on the traditional bounded number-line task likely reflect the growth of task-specific measurement skills rather than changes in the child's understanding of numerical quantities.
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Spinal diffusion tensor imaging: A comprehensive review with emphasis on spinal cord anatomy and clinical applications.
Clin Anat
PUBLISHED: 02-06-2014
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Magnetic resonance imaging technology allows for in vivo visualization of fiber tracts of the central nervous system using diffusion-weighted imaging sequences and data processing referred to as "diffusion tensor imaging" and "diffusion tensor tractography." While protocols for high-fidelity diffusion tensor imaging of the brain are well established, the spinal cord has proven a more difficult target for diffusion tensor methods. Here, we review the current literature on spinal diffusion tensor imaging and tractography with special emphasis on neuroanatomical correlations and clinical applications. Clin. Anat., 2014. © 2014 Wiley Periodicals, Inc.
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Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.
Mol. Psychiatry
PUBLISHED: 02-03-2014
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Psychiatric disorders have clear heritable risk. Several large-scale genome-wide association studies have revealed a strong association between susceptibility for psychiatric disorders, including bipolar disease, schizophrenia and major depression, and a haplotype located in an intronic region of the L-type voltage-gated calcium channel (VGCC) subunit gene CACNA1C (peak associated SNP rs1006737), making it one of the most replicable and consistent associations in psychiatric genetics. In the current study, we used induced human neurons to reveal a functional phenotype associated with this psychiatric risk variant. We generated induced human neurons, or iN cells, from more than 20 individuals harboring homozygous risk genotypes, heterozygous or homozygous non-risk genotypes at the rs1006737 locus. Using these iNs, we performed electrophysiology and quantitative PCR experiments that demonstrated increased L-type VGCC current density as well as increased mRNA expression of CACNA1C in iNs homozygous for the risk genotype, compared with non-risk genotypes. These studies demonstrate that the risk genotype at rs1006737 is associated with significant functional alterations in human iNs, and may direct future efforts at developing novel therapeutics for the treatment of psychiatric disease.Molecular Psychiatry advance online publication, 18 November 2014; doi:10.1038/mp.2014.143.
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SMART DOCS: A New Patient-Centered Outcomes and Coordinated-Care Management Approach for the Future Practice of Sleep Medicine.
Sleep
PUBLISHED: 01-07-2014
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The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control.
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Validation of a semiautomated spinal cord segmentation method.
J Magn Reson Imaging
PUBLISHED: 01-03-2014
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To validate semiautomated spinal cord segmentation in healthy subjects and patients with neurodegenerative diseases and trauma.
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Effect of respiration on the B0 field in the human spinal cord at 3T.
Magn Reson Med
PUBLISHED: 01-03-2014
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Respiration affects the bulk magnetic susceptibility, causing frequency shifts as shown in the brain at 7T. Due to the close proximity of the spine to the lungs, this effect is expected to be even larger in the spinal cord, resulting in detrimental B0 offset. The goal of this study was to quantify the effect of respiration on B0 variation in the spinal cord.
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Vegetation Controls on Weathering Intensity during the Last Deglacial Transition in Southeast Africa.
PLoS ONE
PUBLISHED: 01-01-2014
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Tropical climate is rapidly changing, but the effects of these changes on the geosphere are unknown, despite a likelihood of climatically-induced changes on weathering and erosion. The lack of long, continuous paleo-records prevents an examination of terrestrial responses to climate change with sufficient detail to answer questions about how systems behaved in the past and may alter in the future. We use high-resolution records of pollen, clay mineralogy, and particle size from a drill core from Lake Malawi, southeast Africa, to examine atmosphere-biosphere-geosphere interactions during the last deglaciation (?18-9 ka), a period of dramatic temperature and hydrologic changes. The results demonstrate that climatic controls on Lake Malawi vegetation are critically important to weathering processes and erosion patterns during the deglaciation. At 18 ka, afromontane forests dominated but were progressively replaced by tropical seasonal forest, as summer rainfall increased. Despite indication of decreased rainfall, drought-intolerant forest persisted through the Younger Dryas (YD) resulting from a shorter dry season. Following the YD, an intensified summer monsoon and increased rainfall seasonality were coeval with forest decline and expansion of drought-tolerant miombo woodland. Clay minerals closely track the vegetation record, with high ratios of kaolinite to smectite (K/S) indicating heavy leaching when forest predominates, despite variable rainfall. In the early Holocene, when rainfall and temperature increased (effective moisture remained low), open woodlands expansion resulted in decreased K/S, suggesting a reduction in chemical weathering intensity. Terrigenous sediment mass accumulation rates also increased, suggesting critical linkages among open vegetation and erosion during intervals of enhanced summer rainfall. This study shows a strong, direct influence of vegetation composition on weathering intensity in the tropics. As climate change will likely impact this interplay between the biosphere and geosphere, tropical landscape change could lead to deleterious effects on soil and water quality in regions with little infrastructure for mitigation.
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Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients.
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Pathway analyses implicate glial cells in schizophrenia.
PLoS ONE
PUBLISHED: 01-01-2014
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The quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge.
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Aged erythrocytes: a fine wine or sour grapes?
Br J Anaesth
PUBLISHED: 12-17-2013
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Blood transfusion saves many lives but carries significant risk of injury. Currently, red blood cell (RBC) concentrates can be stored up to 42 days. Concerns have recently been raised about the safety and efficacy of transfusing stored RBCs. Refrigerated storage results in a storage lesion that is reflected by metabolic derangements, RBC shape modification, rheological changes, oxidative injury to lipids and proteins, alterations in oxygen affinity and delivery, increased adhesion of RBCs to endothelial cells, and accumulation of bioactive substances in storage media. In animal models, transfusion of aged, but not fresh, RBCs induces organ injury, inflammation, coagulopathy, and impaired oxygen delivery. A number of clinical studies, mostly observational or retrospective and from a single centre, have reported an association between transfusion of older RBCs and increased clinically significant outcomes, such as increased morbidity and mortality in certain patient populations, including trauma, critical care, and cardiac surgery. Others, however, have failed to indicate an influence of RBC age on outcome. The quality of evidence is currently too poor to make recommendations to change current transfusion practice; however, the transfusion community looks forward to the results of randomized trials currently addressing the long-standing question regarding the effects of RBC storage on clinically significant outcomes.
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Assisted reproduction and risk of depressive relapse: considerations for treatment.
Ann Clin Psychiatry
PUBLISHED: 11-08-2013
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At present, there is a lack of systematic data regarding the risk of relapse of psychiatric disorders in women undergoing infertility treatment. Clinicians would benefit from a systematic study of the biological sequelae of stress and the clinical implications for women with histories of depression or anxiety disorders undergoing treatment for infertility. Women with histories of major depressive disorder may be vulnerable to the stress involved in the process of assisted reproduction, and treatment changes during this time in anticipation of a pregnancy may affect relapse rates.
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Infection duration and inflammatory imbalance are associated with atherosclerotic risk in HIV-infected never-smokers independent of antiretroviral therapy.
AIDS
PUBLISHED: 10-09-2013
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To determine whether the reported increased atherosclerotic risk among HIV-infected individuals is related to antiretroviral therapy (ART) or HIV infection, whether this risk persists in never-smokers, and whether inflammatory profiles are associated with higher risk.
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Identification of discrete functional subregions of the human periaqueductal gray.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-30-2013
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The midbrain periaqueductal gray (PAG) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [Bandler R, Keay KA, Floyd N, Price J (2000) Brain Res 53 (1):95-104]. To examine PAG function in humans, researchers have relied primarily on functional MRI (fMRI), but technological and methodological limitations have prevented researchers from localizing responses to different PAG subregions. We used high-field strength (7-T) fMRI techniques to image the PAG at high resolution (0.75 mm isotropic), which was critical for dissociating the PAG from the greater signal variability in the aqueduct. Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes. In the rostral PAG, activity was localized to lateral and dorsomedial subregions. In caudal PAG, activity was localized to the ventrolateral region. This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals. Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences (e.g., anger and sadness) in a factor analysis, suggesting that each subregion participates in distinct functional circuitry. This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG. The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei.
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On the relativity of relative frequencies.
Atten Percept Psychophys
PUBLISHED: 08-24-2013
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The most prominent models of numerical representation posit that numerical symbols are converted into a single internal, abstract representation prior to estimation and comparison processing. Here, we (1) provide a mathematical analysis of the predictions of the abstract-representation hypothesis, assuming the validity of the analog-representation hypothesis, (2) run a simulation to assess the patterns of data that result from our mathematical analysis, and (3) conduct two experiments to test the predictions of our model, using relative frequencies as inputs. We assess relative frequencies in a typical numerical distance task, whereby participants are presented with two relative frequencies and asked to identify the one that represents the larger quantity. Our data reveal that relative frequencies numerical representations (1) are analog and (2) are scale-specific (i.e., nonabstract).
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A placebo-controlled trial of acetyl-L-carnitine and ?-lipoic acid in the treatment of bipolar depression.
J Clin Psychopharmacol
PUBLISHED: 08-17-2013
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Bipolar disorder may be associated with mitochondrial dysfunction. Therefore, agents that enhance mitochondrial functioning may be efficacious in bipolar disorder. We performed a randomized placebo-controlled trial of the mitochondrial enhancers acetyl-L-carnitine (ALCAR) and ?-lipoic acid (ALA) in patients with bipolar depression, and assessed markers of cerebral energy metabolism using phosphorus magnetic resonance spectroscopy.
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The reliability of the physical examination to guide fluid therapy in adults with severe falciparum malaria: an observational study.
Malar. J.
PUBLISHED: 08-05-2013
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Adults with severe malaria frequently require intravenous fluid therapy to restore their circulating volume. However, fluid must be delivered judiciously as both under- and over-hydration increase the risk of complications and, potentially, death. As most patients will be cared for in a resource-poor setting, management guidelines necessarily recommend that physical examination should guide fluid resuscitation. However, the reliability of this strategy is uncertain.
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Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements.
Am. J. Obstet. Gynecol.
PUBLISHED: 07-25-2013
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The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms.
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Long-term response to combination antiretroviral therapy in HIV-infected children in the Netherlands registered from 1996 to 2012.
AIDS
PUBLISHED: 07-12-2013
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To describe demographic and treatment characteristics of the Dutch vertically HIV-infected paediatric population from 1996 to 2012, and to investigate the long-term virological and immunological response to combination antiretroviral therapy (cART), with emphasis on the influence of age at cART initiation and initial CD4 cell counts.
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Alterations of brain anatomy in mouse model of MDD created by replacement of homologous mouse DNA sequence with an illness-associated 6-base human CREB1 promoter sequence.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 05-30-2013
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We have recently reported the creation and initial characterization of an etiology-based recombinant mouse model of a severe and inherited form of Major Depressive Disorder (MDD). This was achieved by replacing the corresponding mouse DNA sequence with a 6-base DNA sequence from the human CREB1 promoter that is associated with the development of MDD in men and women from families identified by probands with recurrent, early-onset MDD (RE-MDD). Individuals in these families are also at increased risk for childhood developmental disorders and late life neurodegenerative disorders. The current study used three-dimensional magnetic resonance microscopy (3D-MRM) to determine the effect of the resulting humanized mutation of the mouse Creb1 gene on the anatomy of the mouse brain. Homozygous mutant mice manifested prominent increases in the volume and surface area of the lateral ventricles, as well as reduced volume of the anterior corpus callosum, compared to age/sex-matched wild-type mice. No significant genotype effects were observed on the volume or surface area of total brain, or several brain regions sometimes observed to be abnormal in human depression, including hippocampus, amygdala, or striatum. These findings suggest that at least some forms of MDD result from abnormal brain development produced by inherited genetic variants. © 2013 Wiley Periodicals, Inc.
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Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013.
Arch Cardiovasc Dis
PUBLISHED: 04-23-2013
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Direct new oral anticoagulants (NOACs) - inhibitors of thrombin or factor Xa - are intended to be used largely in the treatment of venous thromboembolic disease or the prevention of systematic embolism in atrial fibrillation, instead of vitamin K antagonists. Like any anticoagulant treatment, they are associated with spontaneous or provoked haemorrhagic risk. Furthermore, a significant proportion of treated patients are likely to be exposed to emergency surgery or invasive procedures. Given the absence of a specific antidote, the action to be taken in these situations must be defined. The lack of data means that it is only possible to issue proposals rather than recommendations, which will evolve according to accumulated experience. The proposals presented here apply to dabigatran (Pradaxa(®)) and rivaroxaban (Xarelto(®)); data for apixaban and edoxaban are still scarce. For urgent surgery with haemorrhagic risk, the drug plasma concentration should be less or equal to 30ng/mL for dabigatran and rivaroxaban should enable surgery associated with a high bleeding risk. Beyond that, if possible, the intervention should be postponed by monitoring the drug concentration. The course to follow is then defined according to the NOAC and its concentration. If the anticoagulant dosage is not immediately available, worse propositions, based on the usual tests (prothrombin time and activated partial thromboplastin time), are presented. However, these tests do not really assess drug concentration or the risk of bleeding that depends on it. In case of serious bleeding in a critical organ, the effect of anticoagulant therapy should be reduced using a non-specific procoagulant drug as a first-line approach: activated prothrombin complex concentrate (aPCC) (FEIBA(®) 30-50U/kg) or non-activated PCC (50U/kg). In addition, for any other type of severe haemorrhage, the administration of a procoagulant drug, which is potentially thrombogenic in these patients, is discussed according to the NOAC concentration and the possibilities of mechanical haemostasis.
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Disparate rates of new-onset depression during the menopausal transition in 2 community-based populations: real, or really wrong?
Am. J. Epidemiol.
PUBLISHED: 04-14-2013
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This study took place in eastern Massachusetts and included respondents from the Harvard Study of Moods and Cycles Cohort 1, enrolled between 1995 and 1997, and the Harvard Study of Moods and Cycles Cohort 2, enrolled between 2005 and 2009. In prospectively assessing rates of new-onset depression in 2 populations of late-reproductive-aged women with no Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) lifetime history of depression, we were surprised to find far lower rates of depression in the population with greater racial diversity and lower socioeconomic status, contrary to what had been reported in the scientific literature. To better understand why these disparate results occurred, we assessed confounding and outcome misclassification as potential explanations for the discrepancy. After determining that these were unlikely explanations for the findings, we explored 2 potential sources of selection bias: one induced by self-referral of healthy participants into the study and the other induced by the design of the study itself. We concluded that both types of selection bias were likely to have occurred in this study and could account for the observed difference in rates.
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Rapid Mood-Elevating Effects of Low Field Magnetic Stimulation in Depression.
Biol. Psychiatry
PUBLISHED: 04-01-2013
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We previously reported rapid mood elevation following an experimental magnetic resonance imaging procedure in depressed patients with bipolar disorder (BPD). This prompted the design, construction, and testing of a portable electromagnetic device that reproduces only the rapidly oscillating (1 kHz, <1 V/m) electromagnetic field of the experimental procedure, called low field magnetic stimulation (LFMS).
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7-T MRI of the spinal cord can detect lateral corticospinal tract abnormality in amyotrophic lateral sclerosis.
Muscle Nerve
PUBLISHED: 03-29-2013
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting lower and upper motor neurons. Degeneration of the lateral corticospinal tract (CST) is a key finding in ALS cervical spinal cord autopsies. We hypothesized that in vivo ultra-high-field MRI of the cervical spinal cord can detect abnormality in the CST.
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Guardrail influence on pedestrian crossing behavior at roundabouts.
Accid Anal Prev
PUBLISHED: 03-25-2013
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Pedestrians account for 10-30% of all road accident fatalities in western countries, and therefore efforts to improve pedestrian safety are of major importance. Research can support these efforts in various ways, particularly by studying road crossing patterns, and by exploring pedestrian compliance rates to safety laws and guidelines. This paper focuses on pedestrian crossing behavior at roundabouts. The main goal of the present study was to quantify the effect of guardrails at roundabouts as a tool to direct pedestrians to crosswalks. We examined these effects under various conditions, such as guardrail type, traffic volume, estimated age group, gender, road type, and crosswalk type. The present study was based on field observations at 20 arms at 10 roundabouts in Israel, conducted during 2009. 60 h of video recordings were analyzed. 11,116 pedestrian crossings were observed, of which 2749 (24.7%) were not at a crosswalk, thus violating the law. Binary Logit model results suggest that the rate of violations without guardrail is 20-30% higher than the rate with full guardrail (depending on specific conditions). Compliance rates were found to be higher when traffic volumes were higher. The findings reported in the present study are a valuable contribution to support practical decisions regarding guardrails at roundabouts. Insights from this study on pedestrian crossing patterns at roundabouts can also provide a basis for suggestions of other pedestrian safety improvements.
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Cross-format physical similarity effects and their implications for the numerical cognition architecture.
Cogn Psychol
PUBLISHED: 03-21-2013
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The sound |fa?v| is visually depicted as a written number word "five" and as an Arabic digit "5." Here, we present four experiments--two quantity same/different experiments and two magnitude comparison experiments--that assess whether auditory number words (|fa?v|), written number words ("five"), and Arabic digits ("5") directly activate one another and/or their associated quantity. The quantity same/different experiments reveal that the auditory number words, written number words, and Arabic digits directly activate one another without activating their associated quantity. That is, there are cross-format physical similarity effects but no numerical distance effects. The cross-format magnitude comparison experiments reveal significant effects of both physical similarity and numerical distance. We discuss these results in relation to the architecture of numerical cognition.
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Placing a disrupted degradation motif at the C terminus of proteasome substrates attenuates degradation without impairing ubiquitylation.
J. Biol. Chem.
PUBLISHED: 03-21-2013
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Protein elimination by the ubiquitin-proteasome system requires the presence of a cis-acting degradation signal. Efforts to discern degradation signals of misfolded proteasome substrates thus far revealed a general mechanism whereby the exposure of cryptic hydrophobic motifs provides a degradation determinant. We have previously characterized such a determinant, employing the yeast kinetochore protein Ndc10 as a model substrate. Ndc10 is essentially a stable protein that is rapidly degraded upon exposure of a hydrophobic motif located at the C-terminal region. The degradation motif comprises two distinct and essential elements: DegA, encompassing two amphipathic helices, and DegB, a hydrophobic sequence within the loosely structured C-terminal tail of Ndc10. Here we show that the hydrophobic nature of DegB is irrelevant for the ubiquitylation of substrates containing the Ndc10 degradation motif, but is essential for proteasomal degradation. Mutant DegB, in which the hydrophobic sequence was disrupted, acted as a dominant degradation inhibitory element when expressed at the C-terminal regions of ubiquitin-dependent and -independent substrates of the 26S proteasome. This mutant stabilized substrates in both yeast and mammalian cells, indicative of a modular recognition moiety. The dominant function of the mutant DegB provides a powerful experimental tool for evaluating the physiological implications of stabilization of specific proteasome substrates in intact cells and for studying the associated pathological effects.
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A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503).
Br. J. Cancer
PUBLISHED: 03-13-2013
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The Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a ?-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor.
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The Human Connectome Project and beyond: initial applications of 300 mT/m gradients.
Neuroimage
PUBLISHED: 03-03-2013
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The engineering of a 3 T human MRI scanner equipped with 300 mT/m gradients - the strongest gradients ever built for an in vivo human MRI scanner - was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCPs goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300 mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300 mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients are rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease.
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A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target.
PLoS Genet.
PUBLISHED: 02-28-2013
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We report a genome-wide RNA interference (RNAi) screen for Suppressors of Clozapine-induced Larval Arrest (scla genes) in Caenorhabditis elegans, the first genetic suppressor screen for antipsychotic drug (APD) targets in an animal. The screen identifies 40 suppressors, including the ?-like nicotinic acetylcholine receptor (nAChR) homolog acr-7. We validate the requirement for acr-7 by showing that acr-7 knockout suppresses clozapine-induced larval arrest and that expression of a full-length translational GFP fusion construct rescues this phenotype. nAChR agonists phenocopy the developmental effects of clozapine, while nAChR antagonists partially block these effects. ACR-7 is strongly expressed in the pharynx, and clozapine inhibits pharyngeal pumping. acr-7 knockout and nAChR antagonists suppress clozapine-induced inhibition of pharyngeal pumping. These findings suggest that clozapine activates ACR-7 channels in pharyngeal muscle, leading to tetanus of pharyngeal muscle with consequent larval arrest. No APDs are known to activate nAChRs, but a number of studies indicate that ?7-nAChR agonists may prove effective for the treatment of psychosis. ?-like nAChR signaling is a mechanism through which clozapine may produce its therapeutic and/or toxic effects in humans, a hypothesis that could be tested following identification of the mammalian ortholog of C. elegans acr-7.
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Ultrasound-based teaching of cardiac anatomy and physiology to undergraduate medical students.
Arch Cardiovasc Dis
PUBLISHED: 02-27-2013
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Ultrasonography is a non-invasive imaging modality that offers the opportunity to teach living cardiac anatomy and physiology.
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Ablation of kappa-opioid receptors from brain dopamine neurons has anxiolytic-like effects and enhances cocaine-induced plasticity.
Neuropsychopharmacology
PUBLISHED: 02-27-2013
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Brain kappa-opioid receptors (KORs) are implicated in states of motivation and emotion. Activation of KORs negatively regulates mesolimbic dopamine (DA) neurons, and KOR agonists produce depressive-like behavioral effects. To further evaluate how KOR function affects behavior, we developed mutant mice in which exon 3 of the KOR gene (Oprk1) was flanked with Cre-lox recombination (loxP) sites. By breeding these mice with lines that express Cre-recombinase (Cre) in early embryogenesis (EIIa-Cre) or only in DA neurons (dopamine transporter (DAT)-Cre), we developed constitutive KOR knockouts (KOR(-/-)) and conditional knockouts that lack KORs in DA-containing neurons (DAT-KOR(lox/lox)). Autoradiography demonstrated complete ablation of KOR binding in the KOR(-/-) mutants, and reduced binding in the DAT-KOR(lox/lox) mutants. Quantitative reverse transcription PCR (qPCR) studies confirmed that KOR mRNA is undetectable in the constitutive mutants and reduced in the midbrain DA systems of the conditional mutants. Behavioral characterization demonstrated that these mutant lines do not differ from controls in metrics, including hearing, vision, weight, and locomotor activity. Whereas KOR(-/-) mice appeared normal in the open field and light/dark box tests, DAT-KOR(lox/lox) mice showed reduced anxiety-like behavior, an effect that is broadly consistent with previously reported effects of KOR antagonists. Sensitization to the locomotor-stimulating effects of cocaine appeared normal in KOR(-/-) mutants, but was exaggerated in DAT-KOR(lox/lox) mutants. Increased sensitivity to cocaine in the DAT-KOR(lox/lox) mutants is consistent with a role for KORs in negative regulation of DA function, whereas the lack of differences in the KOR(-/-) mutants suggests compensatory adaptations after constitutive receptor ablation. These mouse lines may be useful in future studies of KOR function.
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Relapse of vasomotor symptoms after discontinuation of the selective serotonin reuptake inhibitor escitalopram: results from the menopause strategies: finding lasting answers for symptoms and health research network.
Menopause
PUBLISHED: 02-26-2013
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Vasomotor symptoms (VMS) recur after discontinuation of hormonal therapy. Selective serotonin reuptake inhibitors (SSRIs) are used increasingly to treat VMS, but whether VMS recur after cessation of SSRI is unknown. We hypothesized that relapse of VMS to baseline levels after SSRI cessation would be common and predicted by menopausal and psychological characteristics.
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Myelin and axon abnormalities in schizophrenia measured with magnetic resonance imaging techniques.
Biol. Psychiatry
PUBLISHED: 02-13-2013
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In schizophrenia (SZ), disturbances in integration of activity among brain regions seem to be as important as abnormal activity of any single region. Brain regions are connected through white matter (WM) tracts, and diffusion tensor imaging has provided compelling evidence for WM abnormalities in SZ. However, diffusion tensor imaging alone cannot currently pinpoint the biological basis of these abnormalities.
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Duloxetine for major depressive disorder and daytime and nighttime hot flashes associated with the menopausal transition.
Maturitas
PUBLISHED: 02-05-2013
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We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety.
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Nineteen-channel receive array and four-channel transmit array coil for cervical spinal cord imaging at 7T.
Magn Reson Med
PUBLISHED: 01-29-2013
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To design and validate a radiofrequency (RF) array coil for cervical spinal cord imaging at 7T.
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Exploration of awareness, knowledge, and perceptions of traumatic brain injury among American youth athletes and their parents.
J Adolesc Health
PUBLISHED: 01-29-2013
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Although much effort is underway by the Centers for Disease Control and Prevention (CDC) and other organizations to highlight the seriousness of traumatic brain injury, including concussions, among young athletes, little is known about how these athletes and their parents view this injury and how much they know about it.
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Functional connectivity of left Heschls gyrus in vulnerability to auditory hallucinations in schizophrenia.
Schizophr. Res.
PUBLISHED: 01-05-2013
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Schizophrenia is a heterogeneous disorder that may consist of multiple etiologies and disease processes. Auditory hallucinations (AH), which are common and often disabling, represent a narrower and more basic dimension of psychosis than schizophrenia. Previous studies suggest that abnormal primary auditory cortex activity is associated with AH pathogenesis. We thus investigated functional connectivity, using a seed in primary auditory cortex, in schizophrenia patients with and without AH and healthy controls, to examine neural circuit abnormalities associated more specifically with AH than the myriad other symptoms that comprise schizophrenia.
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Neuropsychological functioning predicts community outcomes in affective and non-affective psychoses: a 6-month follow-up.
Schizophr. Res.
PUBLISHED: 01-04-2013
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Neurocognitive dysfunction is a major symptom feature of schizophrenia and bipolar disorder. A prognostic relationship between cognition and community outcomes is well-documented in schizophrenia and increasingly recognized in bipolar disorder. However, specific associations among neurocognition, diagnosis, state symptomatology, and community functioning are unclear, and few studies have compared these relationships among patients with affective and non-affective psychoses in the same study. We examined neurocognitive, clinical, and community functioning in a cross-diagnostic sample of patients with psychotic disorders over a 6-month follow-up interval.
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Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder.
Bipolar Disord
PUBLISHED: 01-02-2013
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OBJECTIVES: Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. METHODS: Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. RESULTS: GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21)  = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. CONCLUSIONS: We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition.
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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.

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

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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.