Collar occupancy: A new quantitative imaging tool for morphometric analysis of oligodendrocytes

Publication date: 15 January 2018
Source:Journal of Neuroscience Methods, Volume 294
Author(s): Filipa Bouçanova, André Filipe Maia, Andrea Cruz, Val Millar, Inês Mendes Pinto, João Bettencourt Relvas, Helena Sofia Domingues
BackgroundOligodendrocytes (OL) are the myelinating cells of the central nervous system. OL differentiation from oligodendrocyte progenitor cells (OPC) is accompanied by characteristic stereotypical morphological changes. Quantitative imaging of those morphological alterations during OPC differentiation is commonly used for characterization of new molecules in cell differentiation and myelination and screening of new pro-myelinating drugs. Current available imaging analysis methods imply a non-automated morphology assessment, which is time-consuming and prone to user subjective evaluation.New methodHere, we describe an automated high-throughput quantitative image analysis method entitled collar occupancy that allows morphometric ranking of different stages of in vitro OL differentiation in a high-content analysis format. Collar occupancy is based on the determination of the percentage of area occupied by OPC/OL cytoplasmic protrusions within a defined region that contains the protrusion network, the collar.ResultsWe observed that more differentiated cells have higher collar occupancy and, therefore, this parameter correlates with the degree of OL differentiation.Comparison with existing methodsIn comparison with the method of manual categorization, we found the collar occupancy to be more robust and unbiased. Moreover, when coupled with myelin basic protein (MBP) staining to quantify the percentage of myelinating cells, we were able to evaluate the role of new molecules in OL differentiation and myelination, such as Dusp19 and Kank2.ConclusionsAltogether, we have successfully developed an automated and quantitative method to morphologically characterize OL differentiation in vitro that can be used in multiple studies of OL biology.

Graphical abstract

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Risk of fatigue in cancer patients receiving anti-EGFR monoclonal antibodies: results from a systematic review and meta-analysis of randomized controlled trial

Abstract

Background

To evaluate the association between fatigue and anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first meta-analysis to access the incidence and risk of fatigue associated with anti-EGFR MAbs.

Methods

Electronic databases were searched for randomized controlled trials (RCTs) published up to February 2017. Eligible studies were selected according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Outcomes of quality were summarized in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology.

Results

Thirty-five RCTs (including 15,622 patients) were included; median follow-up ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0 in most of the included trials. For patients receiving anti-EGFR MAbs, the overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%, respectively. Compared with control, anti-EGFR MAbs significantly increased the risk of all-grade fatigue (RR 1.10, 95% CI, 1.05–1.14, moderate-quality evidence) and high-grade fatigue (RR 1.31, 95% CI, 1.19–1.45, moderate-quality evidence). No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type, and median follow-up) on high-grade fatigue were observed. No evidence of publication bias was observed.

Conclusion

The present study suggested that anti-EGFR MAbs may increase the risk of fatigue in cancer patients.

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The Idea of Beauty and Its Biases: Critical Notes on the Aesthetics of Plastic Surgery

Summary: Two biases affect the idea of beauty often embodied in aesthetic surgery. The first one is that the living body is the sum of different parts; the second one claims that beauty results from the sum of beautiful elements. Taken together, these 2 biases explain most of the aesthetic surgery procedures, in which a localized improvement is supposed to impact on the whole body image. In this article, I put into question these 2 problematic assumptions, showing that Western and Eastern aesthetics, on one side, and philosophical reflections, on the other side, support a different conception of beauty. In particular, an alternative idea that opens to authenticity and imperfection and focuses on the living body rather than on the mere anatomical surface is proposed here as a more adequate concept of beauty for aesthetic surgery.

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Diurnal and seasonal trends and source apportionment of redox-active metals in Los Angeles using a novel online metal monitor and Positive Matrix Factorization (PMF)

Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Amirhosein Mousavi, Mohammad H. Sowlat, Constantinos Sioutas
In the present study, we identified the sources of four redox-active metals, including Iron (Fe), Chromium (Cr), Cupper (Cu), and Manganese (Mn) and quantified the contribution of these sources to PM2.5 concentrations in central Los Angeles, California, by employing time-resolved measurements (i.e., a time resolution of 2 h) with a recently developed online metal monitor and Positive Matrix Factorization (PMF). Size distribution of ambient PM (14 nm–10 μm) was measured using the Scanning Mobility Particle Sizer (SMPS) and Optical Particle Sizer (OPS). Auxiliary variables were also collected, including elemental (EC) and organic carbon (OC), gaseous pollutants (NO2 and O3), meteorological parameters (including relative humidity (RH) and temperature), and traffic data (for heavy- (HDVs) and light-duty vehicles (LDVs)). A 4-factor solution was found to be optimum for the chemically-speciated dataset, whereas a 5-factor solution appeared to be most plausible for the size distribution data. The factors included fresh traffic, soil/road dust, urban background aerosol, secondary aerosol, and nucleation (only resolved for the size distribution data). Fresh traffic was the major contributor to Fe and Cu concentrations, whereas Cr was mostly found in the urban background aerosol (reflecting a mixture of small local sources as well as aged traffic emissions), and Mn mostly came from both soil/road dust and was to a lesser degree found in urban background aerosol. Secondary aerosol did not contribute to the concentrations of any of these metals, but was associated with very high loading of OC, as expected. Even though the urban background aerosol and secondary aerosol appeared to be characterized by "aged" particles and have a rather homogeneous spatial distribution, the reactions and processes involved in their formation are entirely different. Our results provide insights into the sources of redox-active metals in central Los Angeles. They also underscore the benefits of novel measurement techniques for PM-bound metals, which could enhance our understanding of the sources of atmospheric aerosols by providing us with measurements with finer time resolutions that otherwise would not have been possible using traditional filter-based measurement techniques.



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Coordinated profiling of stratospheric intrusions and transported pollution by the Tropospheric Ozone Lidar Network (TOLNet) and NASA Alpha Jet experiment (AJAX): Observations and comparison to HYSPLIT, RAQMS, and FLEXPART

Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): A.O. Langford, R.J. Alvarez, J. Brioude, S. Evan, L.T. Iraci, G. Kirgis, S. Kuang, T. Leblanc, M.J. Newchurch, R.B. Pierce, C.J. Senff, E.L. Yates
Ground-based lidars and ozonesondes belonging to the NASA-supported Tropospheric Ozone Lidar Network (TOLNet) are used in conjunction with the NASA Alpha Jet Atmospheric eXperiment (AJAX) to investigate the transport of stratospheric ozone and entrained pollution into the lower troposphere above the United States on May 24–25, 2013. TOLNet and AJAX measurements made in California, Nevada, and Alabama are compared to tropospheric ozone retrievals from the Atmospheric Infrared Sounder (AIRS), to back trajectories from the NOAA Air Resources Laboratory (ARL) Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model, and to analyses from the NOAA/NESDIS Real-time Air Quality Modeling System (RAQMS) and FLEXPART particle dispersion model. The measurements and model analyses show much deeper descent of ozone-rich upper tropospheric/lower stratospheric air above the Desert Southwest than above the Southeast, and comparisons to surface measurements from regulatory monitors reporting to the U.S. EPA Air Quality System (AQS) suggest that there was a much greater surface impact in the Southwest including exceedances of the 2008 National Ambient Air Quality Standard (NAAQS) of 0.075 ppm in both Southern California and Nevada. Our analysis demonstrates the potential benefits to be gained by supplementing the existing surface ozone network with coordinated upper air observations by TOLNet.



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Seizure and cognitive outcomes after resection of glioneuronal tumors in children

Summary

Objective

Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes.

Methods

We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome.

Results

Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043).

Significance

A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs.

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First Direct Evidence of Cue Integration in Reorientation: A New Paradigm

Abstract

There are several models of the use of geometric and feature cues in reorientation (Cheng, Huttenlocher, & Newcombe, ). The adaptive combination approach posits that people integrate cues with weights that depend on cue salience and learning, or, when discrepancies are large, they choose between cues based on these variables (Cheng, Shettleworth, Huttenlocher, & Rieser, ; Newcombe & Huttenlocher, ). In a new paradigm designed to evaluate integration and choice, disoriented participants attempted to return to a heading direction, in a trapezoidal enclosure in which feature and geometric cues both unambiguously specified a heading, but later the feature was moved. With discrepancies greater than 90 degrees, participants choose geometry. With smaller discrepancies, integration appeared in three of five situations; otherwise, participants used geometry alone. Variation depended on direction of feature movement and whether the nearest corner was acute or obtuse. The results have implications for contrasting adaptive combination and modularity theory, and for future research, offering a new paradigm for reorientation research, and for testing cue integration more broadly.

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A review of biomarkers in peri-miniscrew implant crevicular fluid (PMICF)

The temporary anchorage devices (TADs) which include miniscrew implants (MSIs) have evolved as useful armamentarium in the management of severe malocclusions and assist in complex tooth movements. Although a m...

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iSepsis – A 30ml/kg bolus: Yes or No -The Results

The Results of the 30ml/kg Bolus Survey.

EMCrit by Paul Marik.

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New instrumentations in the operating room for sinus surgery

Purpose of review The article reviews the advancements in instrumentation in the operating room that augment the speed, safety or outcomes of endoscopic sinus surgery (ESS). The article aims to update the Rhinologist on recent perioperative instruments that may benefit their practice. Recent findings The greatest advancements in the recent years have been in the field of visualization and optics. The introduction of high definition and ultra high definition 4K camera and screens supported by improvements with three-dimensional and variable angled endoscopes have greatly enhanced the quality and range of the visual information available to the sinus surgeon. This is closely supported by flexibility and enhanced functionality of the powered instrumentation with bipolar, monopolar and malleable blades and ever increasing more powerful burs. Summary Recent years have seen notable developments in the areas of optics, cameras and powered instruments to support the sinus surgeon. This article summarizes these developments and highlights the major benefits of these developments. Correspondence to Anshul Sama, BMedSci, BMBS, FRCS, Consultant Rhinologist and Skull Base Surgeon, Nottingham University Hospital, Nottingham NG7 2UH, UK. Tel: +44 115 9249924; e-mail: anshul.sama@nottingham.ac.uk Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Neural mechanisms of movement planning: motor cortex and beyond

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Karel Svoboda, Nuo Li
Neurons in motor cortex and connected brain regions fire in anticipation of specific movements, long before movement occurs. This neural activity reflects internal processes by which the brain plans and executes volitional movements. The study of motor planning offers an opportunity to understand how the structure and dynamics of neural circuits support persistent internal states and how these states influence behavior. Recent advances in large-scale neural recordings are beginning to decipher the relationship of the dynamics of populations of neurons during motor planning and movements. New behavioral tasks in rodents, together with quantified perturbations, link dynamics in specific nodes of neural circuits to behavior. These studies reveal a neural network distributed across multiple brain regions that collectively supports motor planning. We review recent advances and highlight areas where further work is needed to achieve a deeper understanding of the mechanisms underlying motor planning and related cognitive processes.



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Decision-making behaviors: weighing ethology, complexity, and sensorimotor compatibility

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Ashley L Juavinett, Jeffrey C Erlich, Anne K Churchland
Rodent decision-making research aims to uncover the neural circuitry underlying the ability to evaluate alternatives and select appropriate actions. Designing behavioral paradigms that provide a solid foundation to ask questions about decision-making computations and mechanisms is a difficult and often underestimated challenge. Here, we propose three dimensions on which we can consider rodent decision-making tasks: ethological validity, task complexity, and stimulus-response compatibility. We review recent research through this lens, and provide practical guidance for researchers in the decision-making field.



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Aging Schwann cells: mechanisms, implications, future directions

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Michio Wendell Painter
The aging peripheral nervous system (PNS) is prone to a number of disorders, including the development of neuropathies and increased regenerative failure. Although the basic mechanisms of the aging PNS are still rather murky, recent work has revealed that 'old' Schwann cells acquire a number of dysfunctions in mammals. This review will assess our current knowledge about aging Schwann cells while emphasizing where gaps exist. Indeed, as our understanding of how these peripheral glia contribute to the development, maintenance and regeneration of the PNS becomes increasingly refined, we should also turn our attention to questions of escalating importance in our rapidly greying society: how do Schwann cells change with aging, how might these changes contribute to dysfunction and disease, and what, if anything, might this tell us about the aging central nervous system?



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Myelin dynamics: protecting and shaping neuronal functions

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Aiman S Saab, Klaus-Armin Nave
Myelinating glial cells are well-known to insulate axons and to speed up action potential propagation. Through adjustments in the axonal coverage with myelin, myelin sheath thickness and possibly nodal/internode length oligodendrocytes are involved in fine-tuning the brain's computational power throughout life. Be it motor skill learning or social behaviors in higher vertebrates, proper myelination is critical in shaping brain functions. Neurons rely on their myelinating partners not only for setting conduction speed, but also for regulating the ionic environment and fueling their energy demands with metabolites. Also, long-term axonal integrity and neuronal survival are maintained by oligodendrocytes and loss of this well-coordinated axon–glial interplay contributes to neuropsychiatric diseases. Better insight into how myelination and oligodendrocyte functions are constantly fine-tuned in the adult CNS, which includes sensing of neuronal activity and adjusting glial metabolic support, will be critical for understanding higher brain functions and cognitive decline associated with myelin abnormalities in the aging brain.



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Lateral habenula in the pathophysiology of depression

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Yan Yang, Hao Wang, Ji Hu, Hailan Hu
Depression is a devastating disorder with a combination of diverse symptoms such as low self-esteem, lack of motivation, anhedonia, loss of appetite, low energy, and discomfort without a clear cause. Depression has been suggested to be the result of maladaptive changes in specific brain circuits. Recently, the lateral habenula (LHb) has emerged as a key brain region in the pathophysiology of depression. Increasing evidence from rodent, non-human primate and human studies indicates that the aberrant activity of the LHb is associated with depressive symptoms such as helplessness, anhedonia, and excessive negative focus. Revealing the molecular, cellular and circuit properties of the LHb will help explain how abnormalities in LHb activity are linked to depressive disorders, and shed light on developing novel strategies for depression treatment.



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Specification, plasticity and evolutionary origin of peripheral glial cells

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Maria Eleni Kastriti, Igor Adameyko
Peripheral glia includes predominantly myelinating and non-myelinating Schwann cells in addition to satellite, terminal and enteric glia as well as other unresolved subtypes with localized functions. Of these subtypes, all of them originate from neural crest-derived embryonic Schwann cell precursors (SCPs). Specific gene regulatory networks control neural crest specification and downstream events, including SCP differentiation and myelination. Embryonic SCPs are multipotent and generate neuroendocrine cells, parasympathetic and enteric neurons, melanocytes and other cell types. The evolutionary origin of peripheral Schwann cell lineage is not widely discussed in the literature, despite numerous similarities between central and peripheral glia. Here, we review the major features of the Schwann cell lineage and proceed to an evolutionary discussion around possible relations between central and peripheral glial cells.



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Boundary cap cells in development and disease

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Katarzyna J .Radomska, Piotr Topilko
Broad plasticity of the peripheral glia is an emerging concept during development of the peripheral nervous system (PNS). Recent studies have identified the neural crest-derived boundary caps (BCs), as a multitask stem cell population of the developing PNS. BC progeny migrate along the nerves to provide the major glial component of nerve roots and nerve terminals in the skin. Strikingly, those two locations constitute the privileged sites for development of benign peripheral nerve sheath tumors called neurofibromas in patients with neurofibromatosis type 1 (NF1), making BCs attractive candidates for the 'cell of origin' of this disease. Here, we review these exciting findings, focusing on the origin and novel functions of BCs. We further discuss the heterogeneity of BCs, and address their implication in the pathogenesis of NF1.



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The use of laser Doppler flowmetry to evaluate oral soft tissue blood flow in humans: A review

Publication date: February 2018
Source:Archives of Oral Biology, Volume 86
Author(s): Ayepa Alain Kouadio, Fabienne Jordana, N'goran Justin Koffi, Pierre Le Bars, Assem Soueidan
The objective of this work is to define the conditions for improving the use of laser Doppler flowmetry (LDF) and to determine the limits for the use of this technique.This article systematically reviews the literature on the evaluation of oral soft tissue blood microcirculation by LDF. We analysed the available literature through October 2016 using the database resources Medline/PubMed, the Cochrane Oral Health Group Specialist Trials Register and the ISI Web of Knowledge.Several points emerged from this literature reviewThe use of LDF involves specific constraints; however, the influence of different factors (temperature, tobacco, pressure etc.) must be adequately controlled when using LDF. LDF measurements of soft tissue within the oral cavity vary depending on the anatomical site. In dentistry, LDF can be used to track healing progress in periodontal surgery and to diagnose vascular flow changes in the connective tissue of mucosae covered by a removable prosthesis at an early stage prior to the onset of clinical inflammation signs.



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Expanding the Use of Organs from Hepatitis C-Viremic Donors: The Evidence Continues to Build

No abstract available

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