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Τετάρτη 18 Απριλίου 2018

Polar pesticide contamination of an urban and peri-urban tropical watershed affected by agricultural activities (Yaoundé, Center Region, Cameroon)

Abstract

Urban agriculture is crucial to local populations, but the risk of it contaminating water has rarely been documented. The aim of this study was to assess pesticide contamination of surface waters from the Méfou watershed (Yaoundé, Cameroon) by 32 selected herbicides, fungicides, and insecticides (mainly polar) according to their local application, using both grab sampling and polar organic compounds integrative samplers (POCIS). Three sampling campaigns were conducted in the March/April and October/November 2015 and June/July 2016 rainy seasons in urban and peri-urban areas. The majority of the targeted compounds were detected. The quantification frequencies of eight pesticides were more than 20% with both POCIS and grab sampling, and that of diuron and atrazine reached 100%. Spatial differences in contamination were evidenced with higher contamination in urban than peri-urban rivers. In particular, diuron was identified as an urban contaminant of concern because its concentrations frequently exceeded the European water quality guideline of 0.200 μg/L in freshwater and may thus represent an ecological risk due to a risk quotient > 1 for algae observed in 94% of grab samples. This study raises concerns about the impacts of urban agriculture on the quality of water resources and to a larger extent on the health of the inhabitants of cities in developing countries.

Graphical abstract



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You Can't Fool the Children of the Revolution

Rejuvenation Research, Volume 21, Issue 2, Page 89-90, April 2018.


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Commentary on Some Recent Theses Relevant to Combating Aging: April 2018

Rejuvenation Research, Volume 21, Issue 2, Page 173-177, April 2018.


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Telomerase May Paradoxically Accelerate Aging of the DNA Methylome

Rejuvenation Research, Volume 21, Issue 2, Page 168-172, April 2018.


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The Next Generation of Biomedical and Behavioral Sciences Researchers: Breaking Through [Prepublication Draft].

Since the end of the Second World War, the United States has developed the world's preeminent system for biomedical research, one that has given rise to revolutionary medical advances as well as a dynamic and innovative business sector generating high-quality jobs and powering economic output and exports for the U.S. economy. However, there is a growing concern that the biomedical research enterprise is beset by several core challenges that undercut its vitality, promise, and productivity and that could diminish its critical role in the nation's health and innovation in the biomedical industry.

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Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Chiara Bulgarelli, Anna Blasi, Simon Arridge, Samuel Powell, Carina C.J.M. de Klerk, Victoria Southgate, Sabrina Brigadoi, William Penny, Sungho Tak, Antonia Hamilton
Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies.fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data. This work opens new avenues for future research on effective connectivity in infancy by contributing a data analysis pipeline and guidance for applying DCM to infant fNIRS data.



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Audio-visual speech processing in age-related hearing loss: Stronger integration and increased frontal lobe recruitment

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Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Stephanie Rosemann, Christiane M. Thiel
Hearing loss is associated with difficulties in understanding speech, especially under adverse listening conditions. In these situations, seeing the speaker improves speech intelligibility in hearing-impaired participants. On the neuronal level, previous research has shown cross-modal plastic reorganization in the auditory cortex following hearing loss leading to altered processing of auditory, visual and audio-visual information. However, how reduced auditory input effects audio-visual speech perception in hearing-impaired subjects is largely unknown. We here investigated the impact of mild to moderate age-related hearing loss on processing audio-visual speech using functional magnetic resonance imaging. Normal-hearing and hearing-impaired participants performed two audio-visual speech integration tasks: a sentence detection task inside the scanner and the McGurk illusion outside the scanner. Both tasks consisted of congruent and incongruent audio-visual conditions, as well as auditory-only and visual-only conditions. We found a significantly stronger McGurk illusion in the hearing-impaired participants, which indicates stronger audio-visual integration. Neurally, hearing loss was associated with an increased recruitment of frontal brain areas when processing incongruent audio-visual, auditory and also visual speech stimuli, which may reflect the increased effort to perform the task. Hearing loss modulated both the audio-visual integration strength measured with the McGurk illusion and brain activation in frontal areas in the sentence task, showing stronger integration and higher brain activation with increasing hearing loss. Incongruent compared to congruent audio-visual speech revealed an opposite brain activation pattern in left ventral postcentral gyrus in both groups, with higher activation in hearing-impaired participants in the incongruent condition. Our results indicate that already mild to moderate hearing loss impacts audio-visual speech processing accompanied by changes in brain activation particularly involving frontal areas. These changes are modulated by the extent of hearing loss.



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Fehlender Konsens bei Behandlungskonzepten für makroskopische Rezidive nach radikaler Prostatektomie



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Biophysical modeling of neural plasticity induced by transcranial magnetic stimulation

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Marcus T. Wilson, Ben D. Fulcher, Park K. Fung, P.A. Robinson, Alex Fornito, Nigel C. Rogasch
Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method capable of inducing plastic reorganisation of cortical circuits in humans. Changes in neural activity following TMS are often attributed to synaptic plasticity via process of long-term potentiation and depression (LTP/LTD). However, the precise way in which synaptic processes such as LTP/LTD modulate the activity of large populations of neurons, as stimulated en masse by TMS, are unclear. The recent development of biophysical models, which incorporate the physiological properties of TMS-induced plasticity mathematically, provide an excellent framework for reconciling synaptic and macroscopic plasticity. This article overviews the TMS paradigms used to induce plasticity, and their limitations. It then describes the development of biophysically-based numerical models of the mechanisms underlying LTP/LTD on population-level neuronal activity, and the application of these models to TMS plasticity paradigms, including theta burst and paired associative stimulation. Finally, it outlines how modeling can complement experimental work to improve mechanistic understandings and optimize outcomes of TMS-induced plasticity.



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Investigating the effects of visual distractors on the performance of a motor imagery brain-computer interface

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Zahra Emami, Tom Chau
ObjectivesBrain-computer interfaces (BCIs) allow users to operate a device or application by means of cognitive activity. This technology will ultimately be used in real-world environments which include the presence of distractors. The purpose of the study was to determine the effect of visual distractors on BCI performance.MethodsSixteen able-bodied participants underwent neurofeedback training to achieve motor imagery-guided BCI control in an online paradigm using electroencephalography (EEG) to measure neural signals. Participants then completed two sessions of the motor imagery EEG-BCI protocol in the presence of infrequent, small visual distractors. BCI performance was determined based on classification accuracy.ResultsThe presence of distractors was found to affect motor imagery-specific patterns in mu and beta power. However, the distractors did not significantly affect the BCI classification accuracy; across participants, the mean classification accuracy was 81.5 ± 14% for non-distractor trials, and 78.3 ± 17% for distractor trials.ConclusionThis minimal consequence suggests that the BCI was robust to distractor effects, despite motor imagery-related brain activity being attenuated amid distractors.SignificanceA BCI system that mitigates distraction-related effects may improve the ease of its use and ultimately facilitate the effective translation of the technology from the lab to the home.



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Neural and behavioral changes after the use of hearing aids

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Hanin Karawani, Kimberly A. Jenkins, Samira Anderson
ObjectiveIndividuals with age-related hearing loss (ARHL) can restore some loss of the auditory function with the use of hearing aids (HAs). However, what remains unknown are the physiological mechanisms that underlie how the brain changes with exposure to amplified sounds though the use of HAs. We aimed to examine behavioral and physiological changes induced by HAs.MethodsThirty-five older-adults with moderate ARHL with no history of hearing aid use were fit with HAs tested in aided and unaided conditions, and divided into experimental and control groups. The experimental group used HAs during a period of six months. The control group did not use HAs during this period, but were given the opportunity to use them after the completion of the study. Both groups underwent testing protocols six months apart. Outcome measures included behavioral (speech-in-noise measures, self-assessment questionnaires) and electrophysiological brainstem recordings (frequency-following responses) to the speech syllable /ga/ in two quiet conditions and in six-talker babble noise.ResultsThe experimental group reported subjective benefits on self-assessment questionnaires. Significant physiological changes were observed in the experimental group, specifically a reduction in fundamental frequency magnitude, while no change was observed in controls, yielding a significant time × group interaction. Furthermore, peak latencies remained stable in the experimental group but were significantly delayed in the control group after six months. Significant correlations between behavioral and physiological changes were also observed.ConclusionsThe findings suggest that HAs may alter subcortical processing and offset neural timing delay; however, further investigation is needed to understand cortical changes and HA effects on cognitive processing.SignificanceThe findings of the current study provide evidence for clinicians that the use of HAs may prevent further loss of auditory function resulting from sensory deprivation.



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Oscillatory local field potentials of the nucleus accumbens and the anterior limb of the internal capsule in heroin addicts

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Shunnan Ge, Xinyi Geng, Xuelian Wang, Nan Li, Lei Chen, Xinjing Zhang, Yongzhi Huang, Yang Li, Yukun Chen, Shouyan Wang, Guodong Gao
ObjectivesThe nucleus accumbens (NAc) is known to regulate the motivation and underlie addictive behaviors, and the anterior limb of the internal capsule (ALIC) is involved in several psychiatric disorders. Our study aimed to explore the functions of NAc and ALIC electrophysiologically.MethodsThe local field potentials (LFPs) of the NAc and ALIC were recorded from 7 heroin addicts treated with deep brain stimulation. Correlation analysis was made between LFP powers in various frequency bands and the subjects' neuropsychological test scores; coherence was calculated for the LFPs in NAc and ALIC.ResultsBoth the NAc and ALIC exhibited prominent theta and alpha frequency band activity in the LFP power spectra. Additionally, a distinct beta band peak was detected in the power spectra of ALIC LFPs, which may represent the activity of striatal bridge cells. There was a significant negative correlation between the power of the theta frequency band of ALIC LFPs and visual analogue scale (VAS) scores indicative of cravings (Spearman's ρ = −0.758, P = 0.002), and a significant positive correlation was found between the power of the alpha frequency band of NAc LFPs and subjects' scores on the Hamilton depression inventory (ρ = 0.727, P = 0.005). LFPs of the NAc and ALIC exhibited higher coherence values in the theta and alpha frequency bands.ConclusionsThe results suggest that theta power in the ALIC/dorsal striatum and alpha power in the NAc may be associated with drug cravings and depressive symptoms, respectively, in heroin addicts. For these subjects, the neural activities in the dorsal and ventral striatum were mainly coordinated within the low-frequency band.SignificanceThe study illustrates the neurophysiologic characteristics of heroin addiction and its comorbidities, providing a potential theoretical basis for optimizing deep brain stimulation (DBS) therapy.



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Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients

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Publication date: Available online 17 April 2018
Source:Journal of Autoimmunity
Author(s): Arsene Mekinian, Mathieu Resche-Rigon, Cloé Comarmond, Alessandra Soriano, Joel Constans, Laurent Alric, Patrick Jego, Florian Busato, Matthieu Cabon, Robin Dhote, Lazaro Estibaliz, Isabelle Kone Pault, Cédric Landron, Christian Lavigne, Bertrand Lioger, Martin Michaud, Marc Ruivard, Karim Sacre, Jacques Eric Gottenberg, Francis Gaches, Tiphaine Goulenok, Carlo Salvarani, Patrice Cacoub, Olivier Fain, David Saadoun
ObjectivesTo assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).MethodsWe conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score).ResultsForty-six patients with TA were included, with a median age of 43 years [29–54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2–3] at baseline to 0 [0–1] and 0 at 3 and 6 months, respectively; p < 0.0001). The daily prednisone dose also decreased from 15 mg [8–19] at baseline to 4 mg [5–21] and 5 mg [4.5–9] at 3 and 6 months, respectively (p < 0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% [CI 95%; 0.7–0.95], 72% [CI 95%; 0.55–0.95] and 48% [CI 95%; 0.2–0.1] at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 [CI 95%; 1.08–29], p = 0.041), and C-reactive protein level (HR 1.16 [CI 95%; 1.01–1.31], P = 0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (p = 0.02).ConclusionThis large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.



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False belief and relative clauses in Autism Spectrum Disorders

Publication date: Available online 17 April 2018
Source:Journal of Communication Disorders
Author(s): Stephanie Durrleman, Wolfram Hinzen, Julie Franck




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IGEL Laryngeal Mask Airway Device Effectiveness in Irradiated Necks

Condition:   Laryngeal Masks
Intervention:   Device: IGEL Laryngeal mask
Sponsor:   NHS Lothian
Not yet recruiting

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Comparative Study of Robot BABA Approach and Chest Breast Approach for Lateral Neck Dissection

Conditions:   Thyroid Carcinoma;   Robot Surgery;   Endoscopic Surgery
Interventions:   Device: Robot;   Device: Total endoscopic
Sponsor:   Fujian Medical University
Recruiting

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Percutaneous Ethanol Injection in Combination with Laser Ablation for a 100 ml Partially Cystic Thyroid Nodule.

Related Articles

Percutaneous Ethanol Injection in Combination with Laser Ablation for a 100 ml Partially Cystic Thyroid Nodule.

Case Rep Endocrinol. 2018;2018:8046378

Authors: Negro R, Greco G

Abstract
Until nonsurgical techniques like laser ablation (LA) or radiofrequency became available, patients suffering from large nodules with compressive symptoms were addressed to surgery. We describe the case of a 59-year-old woman with a large, partially cystic thyroid nodule having a volume of about 100 ml. As the patient refused surgery, despite her constant local discomfort, such large partially cystic nodule underwent several percutaneous ethanol injections (PEI) and then was submitted to LA. The combination of these two procedures allowed firstly complete disappearance of the cystic component and secondly a significant reduction of thyroid nodule, which finally measured 17 ml in volume (82% reduction compared to baseline). This case demonstrates that even in very large partially cystic nodules LA preceded by PEI represents a valid alternative to surgery.

PMID: 29662707 [PubMed]



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Immunization of BALB/c mice with a combination of four recombinant Brucella abortus proteins, AspC, Dps, InpB and Ndk, confers a marked protection against a virulent strain of Brucella abortus

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Publication date: Available online 17 April 2018
Source:Vaccine
Author(s): Huynh Tan Hop, Lauren Togonon Arayan, Tran Xuan Ngoc Huy, Alisha Wehdnesday Bernardo Reyes, WonGi Min, Hu Jang Lee, Soo Jong Park, Hong Hee Chang, Suk Kim
In this study, we assessed the protective efficacy of single subunit vaccines, encoded by the B. abortus 544 genes aspC, dps, yaeC and inpB, against B. abortus infection in mice. First, immunization with these antigens, with the exception of the YaeC protein, was found to elicit both humoral and cellular immune responses with IgG2a being dominant over IgG1. In addition, a massive production of IFN-γ but lower degree of IL-10 was observed, suggesting that all three antigens were able to induce predominantly cell-mediated immunity in response to B. abortus infection. Further investigation of a combined subunit vaccine (CSV) consisting of purified AspC, Dps, InpB and Ndk proteins showed a superior protective effect in mice against brucellosis. The intraperitoneal injection of this combination was shown to induce a remarkable production of IFN-γ and IL-2, which occurred in conjunction with an increase of blood CD4+ and CD8+ T cell proportions. In addition, the higher titer of IgG2a compared to IgG1 elicited by this CSV was obtained, suggesting that this CSV induced a typical T-helper-1-dominated immune response in vivo. Furthermore, the protection level induced by this combination was significantly higher than that induced by single antigens and was not significantly different compared to a group immunized with a live attenuated vaccine (RB51). Altogether, our findings suggest that the combination of different immunogenic antigens could be a useful approach for the development of a new, effective and safe brucellosis vaccine that can replace current vaccine strains.



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Impact of elementary school-located influenza vaccinations: A stepped wedge trial across a community

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Publication date: Available online 17 April 2018
Source:Vaccine
Author(s): Peter G. Szilagyi, Stanley Schaffer, Cynthia M. Rand, Nicolas P.N. Goldstein, A. Dirk Hightower, Mary Younge, Ashley Eagan, Aaron Blumkin, Christina S. Albertin, Kristine DiBitetto, Cathleen Concannon, Phyllis Vincelli, Byung-Kwang Yoo, Sharon G. Humiston
BackgroundInfluenza vaccination rates among children are low and novel strategies are needed to raise coverage. We measured the impact of school-located influenza vaccination (SLIV) on coverage, examined whether SLIV substitutes for practice-based influenza vaccination ("substitution"), and estimated whether a second year of experience with SLIV increases its impact.MethodsWe implemented a stepped wedge study design with schools as clusters. In Year 1, we randomly allocated schools to SLIV or control. In Year 2, all schools performed SLIV. We used emails (suburban schools) or backpack fliers (both urban and suburban schools) to notify parents, and offered web-based (suburban) or paper-based vaccination (urban) consent forms. Local health department nurses administered SLIV vaccinations and billed insurers. We analyzed state immunization registry data to measure influenza vaccination rates.Results42 schools (38,078 children) participated over 2 years. Overall vaccination rates were 5 and 7 percentage points higher among SLIV- school children versus control-school children in suburban (aOR 1.36, 95% CI 1.25–1.49 in Years 1–2 SLIV vs. Year 1 control schools) and urban schools (aOR 1.22, 95% CI 1.10–1.36), respectively, adjusting for prior year's vaccination and other covariates. While no substitution occurred among children attending suburban schools, some substitution occurred among children attending urban schools, although overall vaccination rates were still higher in urban schools due to SLIV. Compared to an initial year of SLIV, more children were vaccinated in a second year of SLIV at urban (8.3% vs. 6.8%, aOR 1.24, 95% CI 1.04–1.47) but not suburban schools (3.5% vs. 2.7%, aOR 1.24, 95% CI 0.98–1.57).ConclusionsIn this stepped wedge trial, SLIV increased overall influenza vaccination rates in suburban and urban schools. Some substitution for primary care vaccination occurred in urban settings. A second year of SLIV expanded its reach slightly in urban schools.



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Sorafenib-induced tumor lysis syndrome in a patient with metastatic hepatocellular carcinoma

Publication date: Available online 17 April 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sardar Zakariya Imam, Mohammad Faizan Zahid, Muhammad Asad Maqbool
Tumor lysis syndrome is a potentially lethal complication of chemotherapy, usually associated with aggressive hematologic malignancies. We describe the case of a young patient with metastatic hepatocellular cancer who developed rapid and fatal tumor lysis syndrome following initiation of sorafenib therapy. Although rare with sorafenib therapy for hepatocellular carcinoma, tumor lysis syndrome is serious complication. Patients with a high burden of disease at therapy initiation should have their metabolic parameters measured prior to starting therapy and closely followed for the first 1-2 weeks while being treated.



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Vascular-Derived Vegfa Promotes Cortical Interneuron Migration and Proximity to the Vasculature in the Developing Forebrain

Abstract
Vascular endothelial growth factor (Vegfa) is essential for promoting the vascularization of the embryonic murine forebrain. In addition, it directly influences neural development, although its role in the forming forebrain is less well elucidated. It was recently suggested that Vegfa may influence the development of GABAergic interneurons, inhibitory cells with crucial signaling roles in cortical neuronal circuits. However, the mechanism by which it affects interneuron development remains unknown. Here we investigated the developmental processes by which Vegfa may influence cortical interneuron development by analyzing transgenic mice that ubiquitously express the Vegfa120 isoform to perturb its signaling gradient. We found that interneurons reach the dorsal cortex at mid phases of corticogenesis despite an aberrant vascular network. Instead, endothelial ablation of Vegfa alters cortical interneuron numbers, their intracortical distribution and spatial proximity to blood vessels. We show for the first time that vascular-secreted guidance factors promote early-migrating interneurons in the intact forebrain in vivo and identify a novel role for vascular-Vegfa in this process.

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Dysfunctional Autism Risk Genes Cause Circuit-Specific Connectivity Deficits With Distinct Developmental Trajectories

Abstract
Autism spectrum disorders (ASD) are a set of complex neurodevelopmental disorders for which there is currently no targeted therapeutic approach. It is thought that alterations of genes regulating migration and synapse formation during development affect neural circuit formation and result in aberrant connectivity within distinct circuits that underlie abnormal behaviors. However, it is unknown whether deviant developmental trajectories are circuit-specific for a given autism risk-gene. We used MRI to probe changes in functional and structural connectivity from childhood to adulthood in Fragile-X (Fmr1−/y) and contactin-associated (CNTNAP2−/−) knockout mice. Young Fmr1−/y mice (30 days postnatal) presented with a robust hypoconnectivity phenotype in corticocortico and corticostriatal circuits in areas associated with sensory information processing, which was maintained until adulthood. Conversely, only small differences in hippocampal and striatal areas were present during early postnatal development in CNTNAP2−/− mice, while major connectivity deficits in prefrontal and limbic pathways developed between adolescence and adulthood. These findings are supported by viral tracing and electron micrograph approaches and define 2 clearly distinct connectivity endophenotypes within the autism spectrum. We conclude that the genetic background of ASD strongly influences which circuits are most affected, the nature of the phenotype, and the developmental time course of the associated changes.

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Mapping Cortical Laminar Structure in the 3D BigBrain

Abstract
Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

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Distinct Roles for the Cerebellum, Angular Gyrus, and Middle Temporal Gyrus in Action–Feedback Monitoring

Abstract
Action–feedback monitoring is essential to ensure meaningful interactions with the external world. This process involves generating efference copy-based sensory predictions and comparing these with the actual action-feedback. As neural correlates of comparator processes, previous fMRI studies have provided heterogeneous results, including the cerebellum, angular and middle temporal gyrus. However, these studies usually comprised only self-generated actions. Therefore, they might have induced not only action-based prediction errors, but also general sensory mismatch errors. Here, we aimed to disentangle these processes using a custom-made fMRI-compatible movement device, generating active and passive hand movements with identical sensory feedback. Online visual feedback of the hand was presented with a variable delay. Participants had to judge whether the feedback was delayed. Activity in the right cerebellum correlated more positively with delay in active than in passive trials. Interestingly, we also observed activation in the angular and middle temporal gyri, but across both active and passive conditions. This suggests that the cerebellum is a comparator area specific to voluntary action, whereas angular and middle temporal gyri seem to detect more general intersensory conflict. Correlations with behavior and cerebellar activity nevertheless suggest involvement of these temporoparietal areas in processing and awareness of temporal discrepancies in action-feedback monitoring.

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The Transcription Factor LHX1 Regulates the Survival and Directed Migration of POA-derived Cortical Interneurons

Abstract
The delicate balance of excitation and inhibition is crucial for proper function of the cerebral cortex, relying on the accurate number and subtype composition of inhibitory gamma-aminobutyric (GABA)-expressing interneurons. Various intrinsic and extrinsic factors precisely orchestrate their multifaceted development including the long-range migration from the basal telencephalon to cortical targets as well as interneuron survival throughout the developmental period. Particularly expressed guidance receptors were described to channel the migration of cortical interneurons deriving from the medial ganglionic eminence (MGE) and the preoptic area (POA) along distinct routes. Hence, unveiling the regulatory genetic networks controlling subtype-specific gene expression profiles is key to understand interneuron-specific developmental programs and to reveal causes for associated disorders. In contrast to MGE-derived interneurons, little is known about the transcriptional networks in interneurons born in the POA. Here, we provide first evidence for the LIM-homeobox transcription factor LHX1 as a crucial key player in the post-mitotic development of POA-derived cortical interneurons. By transcriptional regulation of related genes, LHX1 modulates their survival as well as the subtype-specific expression of guidance receptors of the Eph/ephrin family, thereby affecting directional migration and layer distribution in the adult cortex.

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Functional Segregation of the Right Inferior Frontal Gyrus: Evidence From Coactivation-Based Parcellation

Abstract
Previous studies helped unraveling the functional architecture of the human cerebral cortex. However, a comprehensive functional segregation of right lateral prefrontal cortex is missing. Here, we delineated cortical clusters in right area 44 and 45 based on their task-constrained whole-brain activation patterns across neuroimaging experiments obtained from a large database. We identified 5 clusters that differed with respect to their coactivation patterns, which were consistent with resting-state functional connectivity patterns of an independent dataset. Two clusters in the posterior inferior frontal gyrus (IFG) were functionally associated with action inhibition and execution, while two anterior clusters were related to reasoning and social cognitive processes. A fifth cluster was associated with spatial attention. Strikingly, the functional organization of the right IFG can thus be characterized by a posterior-to-anterior axis with action-related functions on the posterior and cognition-related functions on the anterior end. We observed further subdivisions along a dorsal-to-ventral axis in posterior IFG between action execution and inhibition, and in anterior IFG between reasoning and social cognition. The different clusters were integrated in distinct large-scale networks for various cognitive processes. These results provide evidence for a general organization of cognitive processes along axes spanning from more automatic to more complex cognitive processes.

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Modality-specific Subpopulations of Place Fields Coexist in the Hippocampus

Abstract
Hippocampal place cells integrate signals from multiple sensory modalities. However, it is unclear how these different inputs are combined to generate place fields. We investigated how visual spatial cues and an animal's locomotion are integrated by CA3 place cells of Mongolian gerbils. While the animals moved on a virtual linear track, we adapted the gain between the visually projected environment and the treadmill movement. Place cells responded differently to this manipulation. In a subset, place fields were kept in accord with salient visual cues in the virtual environment or reward location, whereas in another subset, place fields were strongly influenced by locomotion. Theta phase precession was present and indistinguishable between the place field types. Theta compression remained intact under gain changes and extended over both types of place field. Hippocampal place cells thus retain strong influence from distinct input streams suggesting a role of the hippocampus CA3 as a multimodal associator on the theta time scale.

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Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain

Abstract
In the mature mammalian brain, the primary somatosensory and motor cortices are known to be spatially organized such that neural activity relating to specific body parts can be somatopically mapped onto an anatomical "homunculus". This organization creates an internal body representation which is fundamental for precise motor control, spatial awareness and social interaction. Although it is unknown when this organization develops in humans, animal studies suggest that it may emerge even before the time of normal birth. We therefore characterized the somatotopic organization of the primary sensorimotor cortices using functional MRI and a set of custom-made robotic tools in 35 healthy preterm infants aged from 31 + 6 to 36 + 3 weeks postmenstrual age. Functional responses induced by somatosensory stimulation of the wrists, ankles, and mouth had a distinct spatial organization as seen in the characteristic mature homunculus map. In comparison to the ankle, activation related to wrist stimulation was significantly larger and more commonly involved additional areas including the supplementary motor area and ipsilateral sensorimotor cortex. These results are in keeping with early intrinsic determination of a somatotopic map within the primary sensorimotor cortices. This may explain why acquired brain injury in this region during the preterm period cannot be compensated for by cortical reorganization and therefore can lead to long-lasting motor and sensory impairment.

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Intracortical Myelination of Heschl’s Gyrus and the Planum Temporale Varies With Heschl’s Duplication Pattern and Rhyming Performance: An Investigation of 440 Healthy Volunteers

Abstract
We investigated, in 445 healthy adults whose Heschl's gyrus (HG) gyrification patterns had been previously identified, how an in vivo MRI marker of intracortical myelination of HG and the planum temporale (PT) varied as a function of HG gyrification pattern and, in cases of duplication, of anatomical characteristics of the second HG (H2). By measuring the MRI T1/T2 ratio in regions of interest covering the first HG (H1), H2 in cases of common stem (H2CSD), or complete posterior duplication (H2CPD) and the PT, we showed that H1 had the highest T1/T2 values, while the PT had the lowest. The major impact of duplication was a decrease in both H1 and PT T1/T2 values in cases of left CPD. Concerning H2, the right and left T1/T2 values of right H2CSD were closer to those of H1, and those of left H2CPD were closer to those of PT. After adjusting for verbal skills, rhyming performance was not associated with T1/T2 values in left regions, but it decreased with increasing right PT T1/T2 values. These results reveal the existence of hemispheric differences in H2 myelination and underline the importance of neuroimaging markers of intracortical myelination for investigating brain structure–function relationships.

https://ift.tt/2vpqDXZ

Foxg1 Regulates the Postnatal Development of Cortical Interneurons

Abstract
Abnormalities in cortical interneurons are closely associated with neurological diseases. Most patients with Foxg1 syndrome experience seizures, suggesting a possible role of Foxg1 in the cortical interneuron development. Here, by conditional deletion of Foxg1, which was achieved by crossing Foxg1fl/fl with the Gad2-CreER line, we found the postnatal distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex were impaired. Further investigations revealed an enhanced dendritic complexity and decreased migration capacity of Foxg1-deficient interneurons, accompanied by remarkable downregulation of Dlx1 and CXCR4. Overexpression of Dlx1 or knock down its downstream Pak3 rescued the differentiation detects, demonstrated that Foxg1 functioned upstream of Dlx1-Pak3 signal pathway to regulate the postnatal development of cortical interneurons. Due to the imbalanced neural circuit, Foxg1 mutants showed increased seizure susceptibility. These findings will improve our understanding of the postnatal development of interneurons and help to elucidate the mechanisms underlying seizure in patients carrying Foxg1 mutations.

https://ift.tt/2HGY4ry

Ventromedial Prefrontal Volume in Adolescence Predicts Hyperactive/Inattentive Symptoms in Adulthood

Abstract
Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = −0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.

https://ift.tt/2vlYj97

Duality of Function: Activation for Meaningless Nonwords and Semantic Codes in the Same Brain Areas

Abstract
Studies of the neural substrates of semantic (word meaning) processing have typically focused on semantic manipulations, with less consideration for potential differences in difficulty across conditions. While the idea that particular brain regions can support multiple functions is widely accepted, studies of specific cognitive domains rarely test for co-location with other functions. Here we start with standard univariate analyses comparing words to meaningless nonwords, replicating our recent finding that this contrast can activate task-positive regions for words, and default-mode regions in the putative semantic network for nonwords, pointing to difficulty effects. Critically, this was followed up with a multivariate analysis to test whether the same areas activated for meaningless nonwords contained semantic information sufficient to distinguish high- from low-imageability words. Indeed, this classification was performed reliably better than chance at 75% accuracy. This is compatible with two non-exclusive interpretations. Numerous areas in the default-mode network are task-negative in the sense of activating for less demanding conditions, and the same areas contain information supporting semantic cognition. Therefore, while areas of the default mode network have been hypothesized to support semantic cognition, we offer evidence that these areas can respond to both domain-general difficulty effects, and to specific aspects of semantics.

https://ift.tt/2HLhwDu

Cross-Task Contributions of Frontobasal Ganglia Circuitry in Response Inhibition and Conflict-Induced Slowing

Abstract
Why are we so slow in choosing the lesser of 2 evils? We considered whether such slowing relates to uncertainty about the value of these options, which arises from the tendency to avoid them during learning, and whether such slowing relates to frontosubthalamic inhibitory control mechanisms. In total, 49 participants performed a reinforcement-learning task and a stop-signal task while fMRI was recorded. A reinforcement-learning model was used to quantify learning strategies. Individual differences in lose–lose slowing related to information uncertainty due to sampling, and independently, to less efficient response inhibition in the stop-signal task. Neuroimaging analysis revealed an analogous dissociation: subthalamic nucleus (STN) BOLD activity related to variability in stopping latencies, whereas weaker frontosubthalamic connectivity related to slowing and information sampling. Across tasks, fast inhibitors increased STN activity for successfully canceled responses in the stop task, but decreased activity for lose–lose choices. These data support the notion that fronto-STN communication implements a rapid but transient brake on response execution, and that slowing due to decision uncertainty could result from an inefficient release of this "hold your horses" mechanism.

https://ift.tt/2EY0QWy

Cocaine Decreases Spontaneous Neuronal Activity and Increases Low-Frequency Neuronal and Hemodynamic Cortical Oscillations

Abstract
Low-frequency oscillations (LFOs) in hemodynamics assessed by fMRI reflect synchronized neuronal activities and are the basis for mapping brain function and its disruption by drugs and disease. Here we assess if cocaine disrupts coupling between neuronal and vascular LFOs by simultaneously measuring cortical field potentials (FP) and cerebral blood flow (CBF) regarding their LFOs (0–1 Hz) spectral bandwidths in the somatosensory cortex of naïve and chronic cocaine-exposed rats at baseline and during cocaine intoxication. While across all conditions the dominant oscillation frequencies for FP and CBF LFOs were ~0.1 Hz, the bandwidth of FP LFOs was about 4.8 ± 0.67 times broader than that of CBF LFOs. Acute cocaine depressed high-frequency FP events but increased the relative intensity of neuronal and hemodynamic LFOs, an effect that was markedly accentuated in magnitude and duration in chronic cocaine-exposed animals. Neuronal LFOs were correlated with CBF LFOs in control animals but not in chronically cocaine-exposed animals, which suggests neurovascular uncoupling. The marked increases in neuronal LFOs with chronic cocaine, which we interpret to reflect increases in neuronal synchronization in the LFOs, and the uncoupling of hemodynamics with resting neuronal activities could contribute to brain dysfunction in cocaine abusers and confound the interpretation of fMRI studies.

https://ift.tt/2HHZiD8

Constitutive Inactivation of the PRRT2 Gene Alters Short-Term Synaptic Plasticity and Promotes Network Hyperexcitability in Hippocampal Neurons

Abstract
Mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function, emphasizing the pathogenic role of the PRRT2 deficiency. In this work, we investigated the phenotype of primary hippocampal neurons obtained from mouse embryos in which the PRRT2 gene was constitutively inactivated. Although PRRT2 is expressed by both excitatory and inhibitory neurons, its deletion decreases the number of excitatory synapses without significantly affecting the number of inhibitory synapses or the nerve terminal ultrastructure. Analysis of synaptic function in primary PRRT2 knockout excitatory neurons by live imaging and electrophysiology showed slowdown of the kinetics of exocytosis, weakened spontaneous and evoked synaptic transmission and markedly increased facilitation. Inhibitory neurons showed strengthening of basal synaptic transmission, accompanied by faster depression. At the network level these complex synaptic effects resulted in a state of heightened spontaneous and evoked activity that was associated with increased excitability of excitatory neurons in both PRRT2 knockout primary cultures and acute hippocampal slices. The data indicate the existence of network instability/hyperexcitability as the possible basis of the paroxysmal phenotypes associated with PRRT2 mutations.

https://ift.tt/2vqwHQ3

Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction

Abstract
Individuals differ in how they perceive, remember, and think. There is evidence for the existence of distinct subgroups that differ in cognitive performance within the older population. However, it is less clear how individual differences in cognition in old age are linked to differences in brain-based measures. We used latent-profile analysis on n-back working-memory (WM) performance to identify subgroups in a large sample of older adults (n = 181; age = 64–68 years). Our analysis identified one larger normal subgroup with higher performance (n = 113; 63%), and a second smaller subgroup (n = 55; 31%) with lower performance. The low-performing subgroup showed weaker load-dependent BOLD modulation and lower connectivity within the fronto-parietal network (FPN) as well as between FPN and striatum during n-back, along with lower FPN connectivity at rest. This group also exhibited lower FPN structural integrity, lower frontal dopamine D2 binding potential, inferior performance on offline WM tests, and a trend-level genetic predisposition for lower dopamine-system efficiency. By contrast, this group exhibited relatively intact episodic memory and associated brain measures (i.e., hippocampal volume, structural, and functional connectivity within the default-mode network). Collectively, these data provide converging evidence for the existence of a group of older adults with impaired WM functioning characterized by reduced cortico-striatal coupling and aberrant cortico-cortical integrity within FPN.

https://ift.tt/2HHytib

Editorial Board

Publication date: 15 June 2018
Source:European Journal of Pharmaceutical Sciences, Volume 118





https://ift.tt/2HKnh4y

The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

Abstract
Mature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids.

https://ift.tt/2vwUoGL

Relationships Between Tau and Glucose Metabolism Reflect Alzheimer’s Disease Pathology in Cognitively Normal Older Adults

Abstract
Tau is associated with hypometabolism in patients with Alzheimer's disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [18F] AV-1451, [18F] Fluorodeoxyglucose, and [11C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB–, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau–glucose metabolism associations separately in PiB–/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB– subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.

https://ift.tt/2HHqTnM

Protein network module-based identification of key pharmacological pathways of Curcuma phaeocaulis Val. acting on hepatitis

Publication date: 15 July 2018
Source:Journal of Ethnopharmacology, Volume 221
Author(s): Yanxiong Gan, Shichao Zheng, Jiaqi Zhao, Chen Zhang, Tianhui Gao, Wan Liao, Qiang Fu, Chaomei Fu
Ethnopharmacological relevanceCurcuma phaeocaulis Val. (CP), as the vital medicines for blood-breaking and disorder-eliminating, has been widely used for hepatitis with good curative effects. Owing to the complexity of traditional Chinese medicine, the pharmacological mechanism of CP remains unclear. To solve this problem, a protein network module-based approach was proposed in this study.Materials and methodsFirstly, the content of active components of CP was detected based on HPLC-DAD. Then the liver protection of CP on Con A-induced hepatitis was validated via the analysis of serum levels of ALT, AST and LDH and histological findings. Next, the targets of CP components obtained from TCMD database were predicted by STITCH and ChEMBL retrieval. In addition, the protein interaction network (PIN) of CP was constructed by Cytoscape based on protein-protein interaction of targets obtained from STRING database. Following the topological analysis of CP PIN, it showed to exhibit the properties of scale-free, small world, and modularity matched with the property of complex biological networks. Finally, the functional modules were identified by gene ontology enrichment analysis based on Molecular Complex Detection algorithm.ResultsThe functional modules indicated that the mechanism of CP acting on the hepatitis is significantly associated with NF-κB and TGF-β signaling pathway. More interestingly, curcumin, demethoxycurcumin and bisdemethoxycurcumin were the main active components of CP acting on the hepatitis, which were demonstrated to be associated with the inflammatory process that occurs during the progression of hepatitis.ConclusionThe protein network module-based approach is an efficient way to investigate the pharmacological mechanisms of CP.

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Effects of anthraquinones from Cassia occidentalis L. on ovalbumin-induced airways inflammation in a mouse model of allergic asthma

Publication date: 15 July 2018
Source:Journal of Ethnopharmacology, Volume 221
Author(s): Wenhao Xu, Meiqun Hu, Qihong Zhang, Jingbo Yu, Weike Su
Ethnopharmacological relevanceCassia occidentalis Linn. is a traditional ayruvedic edible shrub containing anthraquinones (AQs) as the principle active constituents. In folk medicine, it has a variety of uses including treatment of whooping cough ('pertussis') and inflammatory diseases. Despite these applications, limited data are available to validate the effects of C. occidentalis AQs on airways inflammation in asthma.Aim of the studyTo explore the anti-inflammatory potential of AQs extracted from C. occidentalis using an in vivo model of ovalbumin (OVA)-induced asthma.Materials and methodsExtraction and optimization of AQs from C. occidentalis was performed by mechanochemistry. Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN-γ) concentrations, inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were determined. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining. Th1/Th2 cytokine mRNA expression was analyzed using the 2-ΔΔCt method.ResultsTreatment with AQs decreased inflammatory cell counts and production of Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In contrast,Th1 cytokine IFN-γ production in BALF was promoted. AQs also decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological studies demonstrated that AQs substantially inhibited OVA-induced cellular infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung.ConclusionsThese findings demonstrated the inhibitory effects of AQs, derived from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest a promising ethnopharmacological use for AQs in patients with asthma.

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Editorial Board

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Publication date: May 2018
Source:DNA Repair, Volume 65





https://ift.tt/2HGSa9S

Swiss (German) Version of the Actinic Keratosis Quality of Life questionnaire

Background: Actinic keratosis (AK) is a sun-induced skin lesion that may progress to invasive squamous cell carcinoma of the skin. Recently, the Actinic Keratosis Quality of Life questionnaire (AKQoL) was designed for patients with AK in Denmark as a specific quality of life instrument for AK patients. Objective: The objective of this study was to adapt the AKQoL for the German language region of Switzerland and to evaluate its psychometric properties (validity, reliability). Methods: Translation and cultural adaptation of the questionnaire were assessed by using the technique of cognitive interviewing. During the translation process, 34 patients with AK from the Department of Dermatology, University Hospital Zurich, were interviewed in 3 sessions of cognitive interviewing. The translated questionnaire was then distributed together with the Dermatology Life Quality Index (DLQI) to a second group of 113 patients for validation and reliability testing. Within this group, we measured the internal consistency by the Cronbach coefficient α and Spearman correlation coefficient between the AKQoL and the DLQI. Results: The problems encountered during the translation process led to changes in 5 categories as described by Epstein: stylistic changes, change in breadth, change in actual meaning, change in frequency and time frame, change in intensity. We found a Cronbach α of 0.82, an acceptable internal consistency. The Spearman correlation coefficient between total scores of AKQoL and DLQI was 0.57. Conclusion: We culturally adapted and validated a Swiss (German) version of the AKQoL questionnaire applicable for the population of a university center in Switzerland to measure and monitor the quality of life in patients with AK.
Dermatology

https://ift.tt/2JTieiO

Acetylation of Oxidized Base Repair-Initiating NEIL1 DNA Glycosylase Required for Chromatin Bound Repair Complex Formation in Human Genome Increases Cellular Resistance to Oxidative Stress

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Publication date: Available online 17 April 2018
Source:DNA Repair
Author(s): Shiladitya Sengupta, Chunying Yang, Muralidhar L. Hegde, Pavana M. Hegde, Joy Mitra, Arvind Pandey, Arijit Dutta, Abdul Tayyeb Datarwala, Kishor K. Bhakat, Sankar Mitra
Posttranslational modifications of DNA repair proteins have been linked to their function. However, it is not clear if posttranslational acetylation affects subcellular localization of these enzymes. Here, we show that the human DNA glycosylase NEIL1, which is involved in repair of both endo- and exogenously generated oxidized bases via the base excision repair (BER) pathway, is acetylated by histone acetyltransferase p300. Acetylation occurs predominantly at Lys residues 296, 297 and 298 located in NEIL1's disordered C-terminal domain. NEIL1 mutant having the substitution of Lys 296–298 with neutral Ala lost nuclear localization, whereas Lys > Arg substitution (in 3KR mutant) at the same sites did not affect NEIL1's nuclear localization or chromatin binding, presumably due to retention of the positive charge. Although non-acetylated NEIL1 can bind to chromatin, acetylated NEIL1 is exclusively chromatin-bound. NEIL1 acetylation while dispensable for its glycosylase activity enhances it due to increased product release. The acetylation-defective 3KR mutant forms less stable complexes with various chromatin proteins, including histone chaperones and BER/single-strand break repair partners, than the wild-type (WT) NEIL1. We also showed that the repair complex with WT NEIL1 has significantly higher BER activity than the 3KR mutant complex. This is consistent with reduced resistance of non-acetylable mutant NEIL1 expressing cells to oxidative stress relative to cells expressing acetylable WT enzyme. We thus conclude that the major role of acetylable Lys residues in NEIL1 is to stabilize the formation of chromatin-bound repair complexes which protect cells from oxidative stress.



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Scholar : These new articles for Canadian Water Resources Journal / Revue canadienne des ressources hydriques are available online

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Original Articles

Bringing twentieth-century water projects into the twenty-first century: The case for revisiting dam operations in Alberta
Reed D. Benson & Stewart B. Rood
Pages: 1-12 | DOI: 10.1080/07011784.2018.1455539


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Scholar : Shakespeare, Volume 14, Issue 1, April 2018 is now available online on Taylor & Francis Online

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Shakespeare, Volume 14, Issue 1, April 2018 is now available online on Taylor & Francis Online.

SPECIAL ISSUE ON SHAKESPEARE AND THE PUBLIC SPHERE Guest edited by Nigel Wood

This new issue contains the following articles:

Performance

Introduction: Shakespeare's Public Spheres
Nigel Wood
Pages: 1-11 | DOI: 10.1080/17450918.2018.1439093


Theatre Scene and Theatre Public in Early Modern London
Jeffrey S. Doty & Musa Gurnis
Pages: 12-25 | DOI: 10.1080/17450918.2018.1439088


Shakespeare, Ceremony and the Public Sphere of Performance
Alison Findlay
Pages: 26-37 | DOI: 10.1080/17450918.2018.1439089


"No country for old men"? Shakespeare, the Public Sphere and the Gerontological Turn in Theatre
Michael Mangan
Pages: 38-50 | DOI: 10.1080/17450918.2018.1439090


Performing the Public at Shakespeare's Globe
Stephen Purcell
Pages: 51-63 | DOI: 10.1080/17450918.2018.1439091


Shakespeare, Social Media, and the Digital Public Sphere: Such Tweet Sorrow and A Midsummer Night's Dreaming
Erin Sullivan
Pages: 64-79 | DOI: 10.1080/17450918.2018.1439092


Critical Debates and Reviews

Shakespeare and Early Modern Europe: A Critical Survey
Edel Semple & Ema Vyroubalová
Pages: 80-96 | DOI: 10.1080/17450918.2017.1421701


Stage and Picture in the English Renaissance
Crosby Stevens
Pages: 97-98 | DOI: 10.1080/17450918.2017.1422011


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Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.



Thymol attenuates the worsening of atopic dermatitis induced by Staphylococcus aureus membrane vesicles

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Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Hyo Il Kwon, Na Hee Jeong, So Hyun Jun, Joo Hee Son, Shukho Kim, Hyejin Jeon, Sun Chul Kang, Sang Hyun Kim, Je Chul Lee
Staphylococcus aureus membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by S. aureus MVs both in vitro and in vivo. The sub-minimal inhibitory concentrations of thymol disrupted S. aureus MVs. Intact S. aureus MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated S. aureus MVs did not stimulate the expression of these genes. Topical application of thymol-treated S. aureus MVs or treatment with thymol after intact S. aureus MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by S. aureus MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts S. aureus MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by S. aureus MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by S. aureus colonization or infection in the lesions.



https://ift.tt/2HGcp7D

A population-based examination of the co-occurrence and functional correlates of chronic pain and generalized anxiety disorder

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Publication date: Available online 17 April 2018
Source:Journal of Anxiety Disorders
Author(s): Brian Csupak, Jordana L. Sommer, Eric Jacobsohn, Renée El-Gabalawy
ObjectivesThis study aimed to: 1) Establish the prevalence of co-occurring chronic pain conditions (i.e., arthritis, back pain, and migraines) and generalized anxiety disorder (GAD), and 2) Examine levels of pain severity, disability, and work absenteeism among comorbid chronic pain conditions and GAD.MethodsData were analyzed from the 2012 Canadian Community Health Survey–Mental Health (CCHS-MH; N = 25,113). Chi-square analyses assessed whether significant differences existed in pain severity in those with comorbid chronic pain and GAD versus pain conditions alone. Multivariable regressions examined the association between comorbid chronic pain and GAD with functional outcomes.ResultsThe weighted prevalence of GAD among those with chronic migraines, arthritis and back pain was 6.9%, 4.4%, and 6.1% respectively, compared to 2.6% among the entire sample. Severity of pain was increased among those with comorbid chronic pain and GAD compared with chronic pain conditions alone. Migraine was the only pain condition that was significantly associated with disability in our most stringent adjustment model. After controlling for other psychiatric disorders, comorbid GAD and chronic pain was not associated with work absenteeism.ConclusionChronic pain is common among the Canadian population and is associated with substantial disability. Results demonstrated that GAD is prevalent among chronic pain conditions, and comorbidity is associated with greater pain severity. GAD in the context of migraines, in particular, may represent an important treatment target to reduce disability.



https://ift.tt/2J59fd3

“No pain, No gain” still true with immunotherapy: When the finger shows the moon, look at the moon!

Publication date: Available online 17 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): G. Milano, F. Innocenti, B. Lacarelle, J. Ciccolini
There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors. In the current context of precision medicine, and along with the constant quest for identifying predictive biomarkers, close monitoring of treatment-related toxicities could therefore be convenient to help predicting therapeutic response, but presents several caveats. The purpose of this review is to briefly describe these relationships across the different treatments, to comment on possible underlying mechanisms and to comment on possible strategies aiming at exploiting this relationship while keeping the maximal safety ensured in patients with cancer. In particular, this review will investigate on how drug exposure along with germinal and somatic genetic issues does impact on the "No Pain, No Gain" aphorism, and why the temptation to use treatment-related toxicities as a cheap and convenient way to predict clinical outcome or to adapt dosing should be resisted. We do advocate instead for developing comprehensive genomic support along with extensive biomathematical modeling to better customize dosing and shift towards a new "No Pain, Maximal Gain" paradigm.

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https://ift.tt/2qFTmCo

Effects of growth hormone on pregnancy rates of patients with thin endometrium

Abstract

Purpose

To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments.

Materials and methods

Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM).

Results

Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells.

Conclusion

GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.



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Childhood obesity: how long should we wait to predict weight?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2vp2Ver

A tandem mass tag (TMT) proteomic analysis during the early phase of experimental pancreatitis reveals new insights in the disease pathogenesis

Publication date: Available online 17 April 2018
Source:Journal of Proteomics
Author(s): Violeta García-Hernández, Carmen Sánchez-Bernal, Domitille Schvartz, José J. Calvo, Jean-Charles Sanchez, Jesús Sánchez-Yagüe
Changes in the protein expression occurring within the initiation phase of acute pancreatitis (AP) might be vital in the development of this complex disease. However, the exact mechanisms involved in the onset of AP remains elusive and most of our knowledge about the pathobiology of AP comes from animal models. We performed in a rat pancreatitic model a high-throughput shotgun proteomic profiling of the soluble and whole membrane fractions from the pancreas during the early phase of cerulein (Cer)-induced AP. We identified 997 proteins, of which 353 were significantly different (22, 276 or 55 in both, the soluble or the membrane fractions, respectively). Gene Ontology and KEGG PATHWAY analyses revealed that these proteins were implicated in molecular mechanisms relevant to AP pathogenesis, including vesicle-mediated and protein transport, lysosomal and mitochondrial impairment or proteolysis. Numerous metabolic processes were downregulated apparently to reduce energy consumption, and a remarkable increase in inflammatory and stress responses was also highlighted. The proteomic data were verified by immunoblotting of 11 and 7 different soluble or membrane-associated proteins, either novel (VPS29 and MCTS1) or known factors in AP. Also, our first observation of the imbalance of some COP proteins during AP early phase deserves further characterization.Biological significanceAP is one of the most important pathological inflammatory states of the exocrine pancreas but its pathophysiology remains incompletely understood, especially the early acinar events. Proteomic analysis of pancreatic subcellular fractions simplifies protein maps and helps in the identification of new protein alterations and biomarkers characterizing pancreatic tissue damage. Our shotgun approach has not been previously used to profile the early proteomic alterations of the disease, which are considered crucial for its development and for the founding of clinical procedures. Furthermore, our subcellular fractionation protocol allowed us to detect changes in membrane proteins so far overlooked in the proteomic study of AP.Accordingly, using TMT proteomics and bioinformatic tools, we were able to detect significant changes in protein expression related to many pathobiological pathways of acute pancreatitis as from the early phase of the disease. To our knowledge, some of these changes, such as the imbalance of some COP proteins, have never been described in this disease.

Graphical abstract

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Anaesthesia in High-Risk Patients

No abstract available

https://ift.tt/2J18JwP

“No pain, No gain” still true with immunotherapy: When the finger shows the moon, look at the moon!

Publication date: Available online 17 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): G. Milano, F. Innocenti, B. Lacarelle, J. Ciccolini
There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors. In the current context of precision medicine, and along with the constant quest for identifying predictive biomarkers, close monitoring of treatment-related toxicities could therefore be convenient to help predicting therapeutic response, but presents several caveats. The purpose of this review is to briefly describe these relationships across the different treatments, to comment on possible underlying mechanisms and to comment on possible strategies aiming at exploiting this relationship while keeping the maximal safety ensured in patients with cancer. In particular, this review will investigate on how drug exposure along with germinal and somatic genetic issues does impact on the "No Pain, No Gain" aphorism, and why the temptation to use treatment-related toxicities as a cheap and convenient way to predict clinical outcome or to adapt dosing should be resisted. We do advocate instead for developing comprehensive genomic support along with extensive biomathematical modeling to better customize dosing and shift towards a new "No Pain, Maximal Gain" paradigm.

Graphical abstract

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Comparative study of remediation of Cr(VI)-contaminated soil using electrokinetics combined with bioremediation

Abstract

The purpose of this research is to design a new bioremediation-electrokinetic (Bio-EK) remediation process to increase treatment efficiency of chromium contamination in soil. Upon residual chromium analysis, it is shown that traditional electrokinetic-PRB system (control) does not have high efficiency (80.26%) to remove Cr(VI). Bio-electrokinetics of exogenous add with reduction bacteria Microbacterium sp. Y2 and electrokinetics can enhance treatment efficiency Cr(VI) to 90.67% after 8 days' remediation. To optimize the overall performance, integrated bio-electrokinetics were designed by synergy with 200 g humic substances (HS) into the systems. According to our results, Cr(VI) (98.33%) was effectively removed via electrokinetics. Moreover, bacteria and humic substances are natural, sustainable, and economical enhancement agents. The research results indicated that the use of integrated bio-electrokinetics is an effective method to remediate chromium-contaminated soils.



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Effects of 1,540-nm Fractional Nonablative Erbium and 2,940-nm Fractional Ablative Erbium on p53 Epidermal Expression After 3 months: A Split-Face Interventional Study

BACKGROUND Expression of p53 by keratinocytes may be important in the pathogenesis of skin cancer induced by ultraviolet light. OBJECTIVE We used side-by-side nonablative and ablative erbium fractional laser resurfacing to assess the effects on expression of p53 by facial keratinocytes. METHODS Ten female patients (age range, 50–63 years) with Fitzpatrick skin Types I–IV and clinical signs of photoaging underwent erbium fractional laser resurfacing (nonablative, 1,540-nm; ablative, 2,940-nm) on opposite sides of the face. Skin biopsies were obtained before treatment and 3 months after treatment for comparison with control biopsies of face and inner arm, quantifying p53 in immunostained tissue sections. RESULTS Only ablative (2,940-nm) treatments produced a statistically significant reduction in p53 scoring after 3 months. The histologic appearance of skin after ablative resurfacing more closely resembled inner arm skin (rather than facial skin) of control subjects. CONCLUSION Epidermal repopulation with p53-negative keratinocytes through ablative erbium fractional laser resurfacing may diminish the risk of eventual malignancy in photoaged skin. Address correspondence and reprint requests to: Juliano Borges, MD, Rua Almirante Tamandaré 66, 605-Flamengo, Rio de Janeiro-RJ, Brazil CEP 22210-060, or e-mail: julianoborges1@yahoo.com The authors have indicated no significant interest with commercial supporters. The study was approved by the Hospital Universitário Clementino Fraga Filho/Universidade Federal do Rio de Janeiro ethics committee. #Protocol 196/ 09 CEP. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Safety of a Perfluorodecalin-Infused Silicone Patch in Picosecond Laser-Assisted Tattoo Removal: A Retrospective Review

No abstract available

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Review of historical aquatic toxicity and bioconcentration data for the brominated flame retardant tetrabromobisphenol A (TBBPA): effects to fish, invertebrates, algae, and microbial communities

Abstract

This paper summarizes the historical and recent research on the aquatic toxicology and bioconcentration potential of tetrabromobisphenol A (TBBPA), a major flame retardant in electronics. Historical studies on TBBPA are presented in detail, and are compared with more recent research. The historical studies have not been published to date, though they were pivotal in regulatory assessments by the European Union, Canada, and the USA. These assessments have enabled the use of TBBPA as a flame retardant in electronic applications, to the present. The studies were conducted under a Test Rule by the US Environmental Protection Agency in 1987, and were sponsored by member companies of the North American Flame Retardants Alliance (NAFRA) through the American Chemistry Council. The studies were conducted under Good Laboratory Practice procedures, and include 6 acute toxicity tests of TBBPA with fish, invertebrates, algae, and microbes, eight chronic tests, and three bioconcentration studies with fish and invertebrates. Methods and empirical data for each study are detailed in an electronic supplement. Results of the NAFRA studies are compared with recent findings on TBBPA toxicity. Molluscan shell growth may be uniquely sensitive to TBBPA, more sensitive than chronic fish or crustacean toxicity endpoints. Several of the NAFRA studies and several independent studies have reported toxicities exceeding the empirical water solubility limits of TBBPA (in the range of 2.0 mg/L depending on pH). The validity of these results is discussed.



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Τρίτη 17 Απριλίου 2018

Effects of single- and double-layered resorbable membranes and platelet-rich fibrin on bone healing

Abstract

Objectives

Research has been ongoing on achieving optimum bone healing in the reconstruction of bone loss. Clinically, soft tissue migration into the already existing bone defects is the leading cause of unfavourable bone healing. Platelet-rich fibrin, a recent material that is used to promote bone healing, was compared with single- and double-layered resorbable collagen membranes to determine whether a healing protocol which increases patient comfort is possible.

Materials and methods

Sixty adult female Sprague-Dawley rats were used. The rats were divided into five main groups as a sacrification group, a control group, and three experimental groups. The bone defects experimental group 1 were covered with a single-layer collagen membrane, and experimental group 2 were covered with the double-layered collagen membrane. Defects on the experimental group 3 were covered with platelet-rich fibrin membranes which were derived from the sacrification group. The animals in the main groups were also divided into eight subgroups arranged by sacrification periods on day 7 and day 28.

Results

Statistical analysis of our study revealed that new bone formation in experimental group 3 was significantly higher than in other groups. Fibrosis was found to be lower in experimental group 3 than in any other group. No significant differences were found between experimental group 1 and the control group.

Conclusion

Platelet-rich fibrin, which can be used as an autologous membrane which promotes bone healing, yields better clinical result compared to collagen membranes.

Clinical relevance

Histopathologic evaluation has been carried out regarding the effect of platelet-rich fibrin and collagen membranes applied on bone recovery. Our objective is to contribute to barrier membrane studies that continue to guide and accelerate bone recovery.



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Effect of bleaching agent extracts on murine macrophages

Abstract

Objectives

The aim of this study was to evaluate the cytotoxicity and the influence of bleaching agents on immunologically cell surface antigens of murine macrophages in vitro.

Materials and methods

RAW 264.7 cells were exposed to bleaching gel extracts (40% hydrogen peroxide or 20% carbamide peroxide) and different H2O2 concentrations after 1 and 24-h exposure periods and 1-h exposure and 23-h recovery. Tests were performed with and without N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO). Cell viability was determined by MTT assay. The expression of surface markers CD14, CD40, and CD54 with and without LPS stimulation was detected by flow cytometry, while the production of TNF-α was measured by ELISA. Statistical analysis was performed using the Mann-Whitney U test (α = 0.05).

Results

Extracts of bleaching agents were cytotoxic for cells after a 1-h exposure; cells could not recover after 24 h. This effect can be mitigated by the antioxidant NAC and increased by BSO, an inhibitor of glutathione (GSH) synthesis. LPS stimulated expression of all surface markers and TNF-α production. Exposure to bleaching agent extracts and H2O2 leads to a reduction of TNF-α, CD14, and CD40 expression, while the expression of CD54 was upregulated at non-cytotoxic concentrations. Whereas NAC reduced this effect, it was increased in the presence of BSO.

Conclusions

Extracts of bleaching agents were irreversibly cytotoxic to macrophages after a 1-h exposure. Only the expression of CD54 was upregulated. The reactions are mediated by the non-enzymatic antioxidant GSH.

Clinical relevance

The addition of an antioxidant can downregulate unfavorable effects of dental bleaching.



https://ift.tt/2JTVy1Z

Lack of association between ENAM gene polymorphism and dental caries in primary and permanent teeth in Czech children

Abstract

Objectives

The enamelin gene (ENAM) polymorphism (rs12640848) was recently associated with dental caries in primary teeth in Polish children. The aims of the present study were to prove this association in primary dentition and to find a possible effect of this variant on caries development in permanent dentition in Czech children.

Materials and methods

This study comprised 905 Czech children. Totally, 187 children aged 2–6 years with primary dentition [78 healthy subjects (with decayed/missing/filled teeth, dmft = 0) and 109 patients with early childhood caries (ECC; dmft ≥ 1)] were included in this case-control study. In addition, 177 subjects aged 13–15 years without caries (DMFT = 0) and 541 children with dental caries (DMFT ≥ 1) in permanent dentition were selected from the ELSPAC study. Genotype determination of the ENAM polymorphism (rs12640848) was based on the TaqMan method.

Results

No significant differences in the allele or genotype frequencies between the caries-free children and those affected by dental caries were observed in both primary and permanent dentitions.

Conclusions

Lack of association between the ENAM polymorphism (rs12640848) and dental caries in Czech children was detected.

Clinical relevance

Although ENAM is considered as a candidate gene for dental caries, the presence of the ENAM variant (rs12640848) cannot be used as a risk factor of this multifactorial disease in the Czech population.



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Evaluation of the interface between gutta-percha and two types of sealers using scanning electron microscopy (SEM)

Abstract

Objectives

The aim of the present study was to evaluate the adaptation of a calcium silicate bioceramic (BC) sealer with either BC or conventional gutta-percha compared with that of AH Plus sealer in different root canal sections.

Materials and methods

Seventy-two extracted mandibular premolars were divided randomly into six groups. After standardised chemomechanical preparation, four groups were obturated with the BC sealer and BC gutta-percha or conventional gutta-percha, and the other two groups were obturated with AH Plus sealer and conventional gutta-percha either in lateral compaction or in a single cone technique. Each root was sectioned into three sections. An impression was made from each section, and replicas were then made for scanning electron microscopy (SEM) analysis. Areas and interfacial gaps were identified using image analysis software. In addition to descriptive and explorative data analyses, linear regression analysis was performed.

Results

All specimens had measurable interfacial gaps. Significantly fewer gaps were found between conventional gutta-percha and sealer compared to those observed when using the BC gutta-percha (p < 0.001). However, minor interfacial gaps between sealer and dentin were observed with the BC sealer (p = 0.04). The technique of obturation in different root canal sections did not significantly affect the sealer adaptability.

Conclusion

The type of gutta-percha as well as the sealer had a noticeable impact on the adaptability.

Clinical relevance

Different obturation techniques will result in similar outcomes. However, within the limitations of the study, there seems to be no advantage in using the BC gutta-percha.



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