Publication date: June 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 180
Author(s): Afrozul Haq, Sunil J. Wimalawansa, Carsten Carlberg
https://ift.tt/2LvHVH5
Παρασκευή 25 Μαΐου 2018
Highlights from the 6th International Conference on Vitamin D Deficiency, “Nutrition and Human Health”, Abu Dhabi, United Arab Emirates, March 9-10, 2017
Editorial Board
Publication date: June 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 180
https://ift.tt/2KVUcDC
Serum 25-hydroxyvitamin D levels in multiple sclerosis patients from the north of Portugal
Publication date: June 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 180
Author(s): Andreia Bettencourt, Daniela Boleixa, Henrique Reguengo, Raquel Samões, Ernestina Santos, José Carlos Oliveira, Berta Silva, Paulo Pinho Costa, Ana Martins da Silva
Increasing evidence has shown that individuals with Multiple Sclerosis (MS) have lower 25-hydroxyvitamin D [25(OH)D] levels compared to healthy controls. There is no information regarding 25(OH)D levels and MS in Portugal. Therefore the aim of the current study was to examine the levels of 25(OH)D in a group of patients with MS and in healthy matched controls, as well as the association of 25(OH)D levels with disease course, disability and severity. A group of 244 unrelated Portuguese patients, with a definitive diagnosis of MS, and 198 ethnically matched healthy controls were included in the study. A sub-group of patients with recent disease onset was included. Serum 25(OH)D was measured using an electrochemiluminescence binding assay.The mean serum level of 25(OH)D in patients with MS was 39.9±22.0 nmol/L, which was significantly lower (p<0.0001) than those in healthy controls, 55.4±23.4 nmol/L. There was a negative correlation between 25(OH)D levels and EDSS (r=−0.293, p<0.0001) and MSSS scores (r=−0.293, p<0.0001). In multiple logistic regression analysis adjusted for age, gender, disease form, EDSS, disease duration and MSSS, 25(OH)D levels were independently associated with EDSS (p=0.004) and disease duration (p=0.016), and with MSSS (p=0.001).In accordance with the majority of the literature, low serum 25(OH)D levels were associated with susceptibility and disability in MS patients from Portugal. Lower serum 25(OH)D levels were also found in patients with a recent disease onset, supporting vitamin D levels as a risk factor for MS.
https://ift.tt/2J6m7DI
Anticipatory neural dynamics of spatial-temporal orienting of attention in younger and older adults
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Simone G. Heideman, Gustavo Rohenkohl, Joshua J. Chauvin, Clare E. Palmer, Freek van Ede, Anna C. Nobre
Spatial and temporal expectations act synergistically to facilitate visual perception. In the current study, we sought to investigate the anticipatory oscillatory markers of combined spatial-temporal orienting and to test whether these decline with ageing. We examined anticipatory neural dynamics associated with joint spatial-temporal orienting of attention using magnetoencephalography (MEG) in both younger and older adults. Participants performed a cued covert spatial-temporal orienting task requiring the discrimination of a visual target. Cues indicated both where and when targets would appear. In both age groups, valid spatial-temporal cues significantly enhanced perceptual sensitivity and reduced reaction times. In the MEG data, the main effect of spatial orienting was the lateralised anticipatory modulation of posterior alpha and beta oscillations. In contrast to previous reports, this modulation was not attenuated in older adults; instead it was even more pronounced. The main effect of temporal orienting was a bilateral suppression of posterior alpha and beta oscillations. This effect was restricted to younger adults. Our results also revealed a striking interaction between anticipatory spatial and temporal orienting in the gamma-band (60–75 Hz). When considering both age groups separately, this effect was only clearly evident and only survived statistical evaluation in the older adults. Together, these observations provide several new insights into the neural dynamics supporting separate as well as combined effects of spatial and temporal orienting of attention, and suggest that different neural dynamics associated with attentional orienting appear differentially sensitive to ageing.
Graphical abstract
https://ift.tt/2LyDAmi
Population-averaged atlas of the macroscale human structural connectome and its network topology
Source:NeuroImage, Volume 178
Author(s): Fang-Cheng Yeh, Sandip Panesar, David Fernandes, Antonio Meola, Masanori Yoshino, Juan C. Fernandez-Miranda, Jean M. Vettel, Timothy Verstynen
A comprehensive map of the structural connectome in the human brain has been a coveted resource for understanding macroscopic brain networks. Here we report an expert-vetted, population-averaged atlas of the structural connectome derived from diffusion MRI data (N = 842). This was achieved by creating a high-resolution template of diffusion patterns averaged across individual subjects and using tractography to generate 550,000 trajectories of representative white matter fascicles annotated by 80 anatomical labels. The trajectories were subsequently clustered and labeled by a team of experienced neuroanatomists in order to conform to prior neuroanatomical knowledge. A multi-level network topology was then described using whole-brain connectograms, with subdivisions of the association pathways showing small-worldness in intra-hemisphere connections, projection pathways showing hub structures at thalamus, putamen, and brainstem, and commissural pathways showing bridges connecting cerebral hemispheres to provide global efficiency. This atlas of the structural connectome provides representative organization of human brain white matter, complementary to traditional histologically-derived and voxel-based white matter atlases, allowing for better modeling and simulation of brain connectivity for future connectome studies.
https://ift.tt/2KT2qwo
The distribution of pain activity across the human neonatal brain is sex dependent
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Madeleine Verriotis, Laura Jones, Kimberley Whitehead, Maria Laudiano-Dray, Ismini Panayotidis, Hemani Patel, Judith Meek, Lorenzo Fabrizi, Maria Fitzgerald
In adults, there are differences between male and female structural and functional brain connectivity, specifically for those regions involved in pain processing. This may partly explain the observed sex differences in pain sensitivity, tolerance, and inhibitory control, and in the development of chronic pain. However, it is not known if these differences exist from birth. Cortical activity in response to a painful stimulus can be observed in the human neonatal brain, but this nociceptive activity continues to develop in the postnatal period and is qualitatively different from that of adults, partly due to the considerable cortical maturation during this time. This research aimed to investigate the effects of sex and prematurity on the magnitude and spatial distribution pattern of the long-latency nociceptive event-related potential (nERP) using electroencephalography (EEG). We measured the cortical response time-locked to a clinically required heel lance in 81 neonates born between 29 and 42 weeks gestational age (median postnatal age 4 days). The results show that heel lance results in a spatially widespread nERP response in the majority of newborns. Importantly, a widespread pattern is significantly more likely to occur in females, irrespective of gestational age at birth. This effect is not observed for the short latency somatosensory waveform in the same infants, indicating that it is selective for the nociceptive component of the response. These results suggest the early onset of a greater anatomical and functional connectivity reported in the adult female brain, and indicate the presence of pain-related sex differences from birth.
https://ift.tt/2LvvLxX
Heritability estimates of cortical anatomy: The influence and reliability of different estimation strategies
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Sejal Patel, Raihaan Patel, Min Tae M. Park, Mario Masellis, Jo Knight, M. Mallar Chakravarty
Twin study designs have been previously used to investigate the heritability of neuroanatomical measures, such as regional cortical volumes. Volume can be fractionated into surface area and cortical thickness, where both measures are considered to have independent genetic and environmental bases. Region of interest (ROI) and vertex-wise approaches have been used to calculate heritability of cortical thickness and surface area in twin studies. In our study, we estimate heritability using the Human Connectome Project magnetic resonance imaging dataset composed of healthy young twin and non-twin siblings (mean age of 29, sample size of 757). Both ROI and vertex-wise methods were used to compare regional heritability of cortical thickness and surface area. Heritability estimates were controlled for age, sex, and total ipsilateral surface area or mean cortical thickness. In both approaches, heritability estimates of cortical thickness and surface area were lower when accounting for average ipsilateral cortical thickness and total surface area respectively. When comparing both approaches at a regional level, the vertex-wise approach showed higher surface area and lower cortical thickness heritability estimates compared to the ROI approach. The calcarine fissure had the highest surface area heritability estimate (ROI: 44%, vertex-wise: 50%) and posterior cingulate gyrus had the highest cortical thickness heritability (ROI: 50%, vertex-wise 40%). We also observed that limitations in image processing and variability in spatial averaging errors based on regional size may make obtaining true estimates of cortical thickness and surface area challenging in smaller regions. It is important to identify which approach is best suited to estimate heritability based on the research hypothesis and the size of the regions being investigated.
https://ift.tt/2KT2jRu
Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Omer F. Gulban, Federico De Martino, An T. Vu, Essa Yacoub, Kamil Uğurbil, Christophe Lenglet
Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which provide complementary (e.g. to anatomical and functional MRI) microstructural information about the cortex architectonic. Several ex-vivo and in-vivo MRI studies have recently addressed this question, however predominantly with an emphasis on specific cortical areas. There is currently no whole brain in-vivo data leveraging multi-shell diffusion MRI acquisition at high spatial resolution, and depth dependent analysis, to characterize the complex organization of cortical fibers. Here, we present unique in-vivo human 7T diffusion MRI data, and a dedicated cortical depth dependent analysis pipeline. We leverage the high spatial (1.05 mm isotropic) and angular (198 diffusion gradient directions) resolution of this whole brain dataset to improve cortical fiber orientations mapping, and study neurites (axons and/or dendrites) trajectories across cortical depths. Tangential fibers in superficial cortical depths and crossing fiber configurations in deep cortical depths are identified. Fibers gradually inserting into the gyral walls are visualized, which contributes to mitigating the gyral bias effect. Quantitative radiality maps and histograms in individual subjects and cortex-based aligned datasets further support our results.
https://ift.tt/2J7CFuU
Quantifying fast optical signal and event-related potential relationships during a visual oddball task
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Nicole Proulx, Ali-Akbar Samadani, Tom Chau
Event-related potentials (ERPs) have previously been used to confirm the existence of the fast optical signal (FOS) but validation methods have mainly been limited to exploring the temporal correspondence of FOS peaks to those of ERPs. The purpose of this study was to systematically quantify the relationship between FOS and ERP responses to a visual oddball task in both time and frequency domains. Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) sensors were co-located over the prefrontal cortex while participants performed a visual oddball task. Fifteen participants completed 2 data collection sessions each, where they were instructed to keep a mental count of oddball images. The oddball condition produced a positive ERP at 200 ms followed by a negativity 300–500 ms after image onset in the frontal electrodes. In contrast to previous FOS studies, a FOS response was identified only in DC intensity signals and not in phase delay signals. A decrease in DC intensity was found 150–250 ms after oddball image onset with a 400-trial average in 10 of 15 participants. The latency of the positive 200 ms ERP and the FOS DC intensity decrease were significantly correlated for only 6 (out of 15) participants due to the low signal-to-noise ratio of the FOS response. Coherence values between the FOS and ERP oddball responses were found to be significant in the 3–5 Hz frequency band for 10 participants. A significant Granger causal influence of the ERP on the FOS oddball response was uncovered in the 2–6 Hz frequency band for 7 participants. Collectively, our findings suggest that, for a majority of participants, the ERP and the DC intensity signal of the FOS are spectrally coherent, specifically in narrow frequency bands previously associated with event-related oscillations in the prefrontal cortex. However, these electro-optical relationships were only found in a subset of participants. Further research on enhancing the quality of the event-related FOS signal is required before it can be practically exploited in applications such as brain-computer interfacing.
https://ift.tt/2KT2aNW
Subregional volumes of the hippocampus in relation to cognitive function and risk of dementia
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Tavia E. Evans, Hieab H.H. Adams, Silvan Licher, Frank J. Wolters, Aad van der Lugt, M. Kamran Ikram, Michael J. O'Sullivan, Meike W. Vernooij, M. Arfan Ikram
BackgroundTotal hippocampal volume has been consistently linked to cognitive function and dementia. Yet, given its complex and parcellated internal structure, the role of subregions of the hippocampus in cognition and risk of dementia remains relatively underexplored. We studied subregions of the hippocampus in a large population-based cohort to further understand their role in cognitive impairment and dementia risk.MethodsWe studied 5035 dementia- and stroke-free persons from the Rotterdam Study, aged over 45 years. All participants underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Automatic segmentation of the hippocampus and 12 of its subregions was performed using the FreeSurfer software (version 6.0). A cognitive test battery was performed, and participants were followed up for the development of dementia until 2015. Associations of hippocampal subregion volumes with cognition and incident dementia were examined using linear and Cox regression models, respectively. All analyses were adjusted for age, sex, education, and total hippocampal volume.ResultsMean age was 64.3 years (SD 10.6) with 56% women. Smaller volumes of the hippocampal fimbria, presubiculum and subiculum showed the strongest associations with poor performance on several cognitive domains, including executive function but not memory. During a mean follow-up of 5.5 years, 76 persons developed dementia. Smaller subiculum volume was associated with risk of dementia adjusted for total volume (hazard ratio per SD decrease in volume: 1.75, 95% confidence interval 1.35; 2.26).ConclusionsIn a community-dwelling non-demented population, we describe patterns of association between hippocampal subregions with cognition and risk of dementia. Specifically, the subiculum was associated with both poorer cognition and higher risk of dementia.
https://ift.tt/2Lw64xo
Multivoxel pattern similarity suggests the integration of temporal duration in hippocampal event sequence representations
Source:NeuroImage, Volume 178
Author(s): Sathesan Thavabalasingam, Edward B. O'Neil, Andy C.H. Lee
Recent rodent work suggests the hippocampus may provide a temporal representation of event sequences, in which the order of events and the interval durations between them are encoded. There is, however, limited human evidence for the latter, in particular whether the hippocampus processes duration information pertaining to the passage of time rather than qualitative or quantitative changes in event content. We scanned participants while they made match-mismatch judgements on each trial between a study sequence of events and a subsequent test sequence. Participants explicitly remembered event order or interval duration information (Experiment 1), or monitored order only, with duration being manipulated implicitly (Experiment 2). Hippocampal study-test pattern similarity was significantly reduced by changes to order or duration in mismatch trials, even when duration was processed implicitly. Our findings suggest the human hippocampus processes short intervals within sequences and support the idea that duration information is integrated into hippocampal mnemonic representations.
https://ift.tt/2KT1TdS
Brain network segregation and integration during an epoch-related working memory fMRI experiment
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Peter Fransson, Björn C. Schiffler, William Hedley Thompson
The characterization of brain subnetwork segregation and integration has previously focused on changes that are detectable at the level of entire sessions or epochs of imaging data. In this study, we applied time-varying functional connectivity analysis together with temporal network theory to calculate point-by-point estimates in subnetwork segregation and integration during an epoch-based (2-back, 0-back, baseline) working memory fMRI experiment as well as during resting-state. This approach allowed us to follow task-related changes in subnetwork segregation and integration at a high temporal resolution. At a global level, the cognitively more taxing 2-back epochs elicited an overall stronger response of integration between subnetworks compared to the 0-back epochs. Moreover, the visual, sensorimotor and fronto-parietal subnetworks displayed characteristic and distinct temporal profiles of segregation and integration during the 0- and 2-back epochs. During the interspersed epochs of baseline, several subnetworks, including the visual, fronto-parietal, cingulo-opercular and dorsal attention subnetworks showed pronounced increases in segregation. Using a drift diffusion model we show that the response time for the 2-back trials are correlated with integration for the fronto-parietal subnetwork and correlated with segregation for the visual subnetwork. Our results elucidate the fast-evolving events with regard to subnetwork integration and segregation that occur in an epoch-related task fMRI experiment. Our findings suggest that minute changes in subnetwork integration are of importance for task performance.
https://ift.tt/2LvA7VN
Model-free and model-based reward prediction errors in EEG
Source:NeuroImage, Volume 178
Author(s): Thomas D. Sambrook, Ben Hardwick, Andy J. Wills, Jeremy Goslin
Learning theorists posit two reinforcement learning systems: model-free and model-based. Model-based learning incorporates knowledge about structure and contingencies in the world to assign candidate actions with an expected value. Model-free learning is ignorant of the world's structure; instead, actions hold a value based on prior reinforcement, with this value updated by expectancy violation in the form of a reward prediction error. Because they use such different learning mechanisms, it has been previously assumed that model-based and model-free learning are computationally dissociated in the brain. However, recent fMRI evidence suggests that the brain may compute reward prediction errors to both model-free and model-based estimates of value, signalling the possibility that these systems interact. Because of its poor temporal resolution, fMRI risks confounding reward prediction errors with other feedback-related neural activity. In the present study, EEG was used to show the presence of both model-based and model-free reward prediction errors and their place in a temporal sequence of events including state prediction errors and action value updates. This demonstration of model-based prediction errors questions a long-held assumption that model-free and model-based learning are dissociated in the brain.
https://ift.tt/2KVj2U9
The temporal evolution of conceptual object representations revealed through models of behavior, semantics and deep neural networks
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): B.B. Bankson, M.N. Hebart, I.I.A. Groen, C.I. Baker
Visual object representations are commonly thought to emerge rapidly, yet it has remained unclear to what extent early brain responses reflect purely low-level visual features of these objects and how strongly those features contribute to later categorical or conceptual representations. Here, we aimed to estimate a lower temporal bound for the emergence of conceptual representations by defining two criteria that characterize such representations: 1) conceptual object representations should generalize across different exemplars of the same object, and 2) these representations should reflect high-level behavioral judgments. To test these criteria, we compared magnetoencephalography (MEG) recordings between two groups of participants (n = 16 per group) exposed to different exemplar images of the same object concepts. Further, we disentangled low-level from high-level MEG responses by estimating the unique and shared contribution of models of behavioral judgments, semantics, and different layers of deep neural networks of visual object processing. We find that 1) both generalization across exemplars as well as generalization of object-related signals across time increase after 150 ms, peaking around 230 ms; 2) representations specific to behavioral judgments emerged rapidly, peaking around 160 ms. Collectively, these results suggest a lower bound for the emergence of conceptual object representations around 150 ms following stimulus onset.
https://ift.tt/2LxY4f1
A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks
Source:NeuroImage, Volume 178
Author(s): Rafael Ceschin, Alexandria Zahner, William Reynolds, Jenna Gaesser, Giulio Zuccoli, Cecilia W. Lo, Vanathi Gopalakrishnan, Ashok Panigrahy
Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well-defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 ± 0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging.
https://ift.tt/2KVRaPA
Individualized tractography-based parcellation of the globus pallidus pars interna using 7T MRI in movement disorder patients prior to DBS surgery
Source:NeuroImage, Volume 178
Author(s): Rémi Patriat, Scott E. Cooper, Yuval Duchin, Jacob Niederer, Christophe Lenglet, Joshua Aman, Michael C. Park, Jerrold L. Vitek, Noam Harel
The success of deep brain stimulation (DBS) surgeries for the treatment of movement disorders relies on the accurate placement of an electrode within the motor portion of subcortical brain targets. However, the high number of electrodes requiring relocation indicates that today's methods do not ensure sufficient accuracy for all patients. Here, with the goal of aiding DBS targeting, we use 7 Tesla (T) MRI data to identify the functional territories and parcellate the globus pallidus pars interna (GPi) into motor, associative and limbic regions in individual subjects.7 T MRI scans were performed in seventeen patients (prior to DBS surgery) and one healthy control. Tractography-based parcellation of each patient's GPi was performed. The cortex was divided into four masks representing motor, limbic, associative and "other" regions. Given that no direct connections between the GPi and the cortex have been shown to exist, the parcellation was carried out in two steps: 1) The thalamus was parcellated based on the cortical targets, 2) The GPi was parcellated using the thalamus parcels derived from step 1. Reproducibility, via repeated scans of a healthy subject, and validity of the findings, using different anatomical pathways for parcellation, were assessed. Lastly, post-operative imaging data was used to validate and determine the clinical relevance of the parcellation.The organization of the functional territories of the GPi observed in our individual patient population agrees with that previously reported in the literature: the motor territory was located posterolaterally, followed anteriorly by the associative region, and further antero-ventrally by the limbic territory. While this organizational pattern was observed across patients, there was considerable variability among patients. The organization of the functional territories of the GPi was remarkably reproducible in intra-subject scans. Furthermore, the organizational pattern was observed consistently by performing the parcellation of the GPi via the thalamus and via a different pathway, going through the striatum. Finally, the active therapeutic contact of the DBS electrode, identified with a combination of post-operative imaging and post-surgery DBS programming, overlapped with the high-probability "motor" region of the GPi as defined by imaging-based methods.The consistency, validity, and clinical relevance of our findings have the potential for improving DBS targeting, by increasing patient-specific knowledge of subregions of the GPi to be targeted or avoided, at the stage of surgical planning, and later, at the stage when stimulation is adjusted.
https://ift.tt/2LxXVIv
Handedness-dependent functional organizational patterns within the bilateral vestibular cortical network revealed by fMRI connectivity based parcellation
Source:NeuroImage, Volume 178
Author(s): V. Kirsch, R. Boegle, D. Keeser, E. Kierig, B. Ertl-Wagner, T. Brandt, M. Dieterich
Current evidence points towards a vestibular cortex that involves a multisensory bilateral temporo-parietal-insular network with a handedness-dependent hemispheric lateralization. This study aimed to identify handedness-dependent organizational patterns of (lateralized and non-lateralized) functional subunits within the human vestibular cortex areas. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state functional MRI (fMRI). The data was analyzed in four major steps using a functional connectivity based parcellation (fCBP) approach: (1) independent component analysis (ICA) on a whole brain level to identify different resting state networks (RSN); (2) creation of a vestibular informed mask from four whole brain ICs that included reference coordinates of the vestibular network extracted from meta-analyses of vestibular neuroimaging experiments; (3) Re-ICA confined to the vestibular informed mask; (4) cross-correlation of the activated voxels within the vestibular subunits (parcels) to each other (P-to-P) and to the whole-brain RSN (P-to-RSN).This approach disclosed handedness-dependency, inter-hemispheric symmetry, the scale of connectedness to major whole brain RSN and the grade of spatial overlap of voxels within parcels (common/unique) as meaningful discriminatory organizational categories within the vestibular cortex areas. This network consists of multiple inter-hemisphere symmetric (not lateralized), well-connected (many RSN-assignments) multisensory areas (or hubs; e.g., superior temporal gyrus, temporo-parietal intersection) organized around an asymmetric (lateralized, "dominant") and functionally more specialized (few RSN-assignments) core region in the parieto-insular cortex. The latter is in the middle, posterior and inferior insula. In conclusion, the bilateral cortical vestibular network contains not only a handedness-dependent lateralized central region concentrated in the right hemisphere in right-handers and left hemisphere in left-handers, but also surrounding inter-hemisphere symmetric multisensory vestibular areas that seem to be functionally influenced by their neighboring sensory systems (e.g., temporo-parietal intersection by the visual system). One may speculate that the development of an asymmetrical organized vestibular subsystem reflects a more recent phylogenetic evolution of various multisensory vestibular functions. The right hemispheric dominance of spatial orientation and its disorders, spatial neglect and pusher syndrome, may serve as examples.
https://ift.tt/2KWfiBU
Mutual connectivity analysis of resting-state functional MRI data with local models
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Adora M. DSouza, Anas Z. Abidin, Udaysankar Chockanathan, Giovanni Schifitto, Axel Wismüller
Functional connectivity analysis of functional MRI (fMRI) can represent brain networks and reveal insights into interactions amongst different brain regions. However, most connectivity analysis approaches adopted in practice are linear and non-directional. In this paper, we demonstrate the advantage of a data-driven, directed connectivity analysis approach called Mutual Connectivity Analysis using Local Models (MCA-LM) that approximates connectivity by modeling nonlinear dependencies of signal interaction, over more conventionally used approaches, such as Pearson's and partial correlation, Patel's conditional dependence measures, etcetera. We demonstrate on realistic simulations of fMRI data that, at long sampling intervals, i.e. high repetition time (TR) of fMRI signals, MCA-LM performs better than or comparable to correlation-based methods and Patel's measures. However, at fast image acquisition rates corresponding to low TR, MCA-LM significantly outperforms these methods. This insight is particularly useful in the light of recent advances in fast fMRI acquisition techniques. Methods that can capture the complex dynamics of brain activity, such as MCA-LM, should be adopted to extract as much information as possible from the improved representation. Furthermore, MCA-LM works very well for simulations generated at weak neuronal interaction strengths, and simulations modeling inhibitory and excitatory connections as it disentangles the two opposing effects between pairs of regions/voxels. Additionally, we demonstrate that MCA-LM is capable of capturing meaningful directed connectivity on experimental fMRI data. Such results suggest that it introduces sufficient complexity into modeling fMRI time-series interactions that simple, linear approaches cannot, while being data-driven, computationally practical and easy to use. In conclusion, MCA-LM can provide valuable insights towards better understanding brain activity.
https://ift.tt/2LxXLkn
Extracting orthogonal subject- and condition-specific signatures from fMRI data using whole-brain effective connectivity
Source:NeuroImage, Volume 178
Author(s): Vicente Pallarés, Andrea Insabato, Ana Sanjuán, Simone Kühn, Dante Mantini, Gustavo Deco, Matthieu Gilson
The study of brain communication based on fMRI data is often limited because such measurements are a mixture of session-to-session variability with subject- and condition-related information. Disentangling these contributions is crucial for real-life applications, in particular when only a few recording sessions are available. The present study aims to define a reliable standard for the extraction of multiple signatures from fMRI data, while verifying that they do not mix information about the different modalities (e.g., subjects and conditions such as tasks performed by them). In particular, condition-specific signatures should not be contaminated by subject-related information, since they aim to generalize over subjects. Practically, signatures correspond to subnetworks of directed interactions between brain regions (typically 100 covering the whole brain) supporting the subject and condition identification for single fMRI sessions. The key for robust prediction is using effective connectivity instead of functional connectivity. Our method demonstrates excellent generalization capabilities for subject identification in two datasets, using only a few sessions per subject as reference. Using another dataset with resting state and movie viewing, we show that the two signatures related to subjects and tasks correspond to distinct subnetworks, which are thus topologically orthogonal. Our results set solid foundations for applications tailored to individual subjects, such as clinical diagnostic.
https://ift.tt/2KWCDTI
The protective effects of selenium supplementation on ambient PM 2.5- induced cardiovascular injury in rats
Abstract
Substantial epidemiological and experimental studies have shown that ambient fine particulate matter (PM2.5) exposure can lead to myocardial damage in human and animal through the mechanism of inflammation and oxidative stress. The purpose of the current study was to investigate whether selenium yeast (SeY) supplementation could prevent cardiovascular injury caused by PM2.5 in rats. Fifty-six Sprague-Dawley rats were randomly divided into seven groups: saline control group; solvent control group, low-, middle-, and high-dose Se pretreatment groups, PM2.5 exposure group, and high-dose Se control group. The rats were pretreated with different concentration of dietary SeY for 28 days, then were exposed to PM2.5 by intratracheal instillation every other day, a total of three times. The levels of inflammatory markers (tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), soluble intercellular adhesion molecule-1 (sICAM-1), and oxidative responses-related indicators total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured in blood and myocardium of the left ventricle. The results showed that although PM2.5 caused a decrease of T-AOC, T-AOD, and GSH-Px and increase of MDA and sICM-1, pretreatment with SeY induced a dose-dependent increase in these anti-oxidative indicators and a decrease in oxidative indicators. In addition, the levels of TNF-α and IL-1β in Se pretreatment groups were significantly lower than that in PM2.5 exposure group. The results indicated that Se supplementation could effectively prevent cardiovascular inflammation and oxidative stress induced by PM2.5. The results also indicated that the nutritional supplementation might be an effective way to protecting people's health from air pollution.
https://ift.tt/2sb7hkw
Differential contributions of cortical thickness and surface area to trait impulsivity in healthy young adults
Publication date: 17 September 2018
Source:Behavioural Brain Research, Volume 350
Author(s): Katharina M. Kubera, Mike M. Schmitgen, Klaus H. Maier-Hein, Philipp A. Thomann, Dusan Hirjak, Robert C. Wolf
BackgroundImpulsivity is an essential human personality trait and highly relevant for the development of several mental disorders. There is evidence that impulsivity is heritable, yet little is known about neural correlates reflecting early brain development. Here, we address the question whether motor, attentional and non-planning components, as reflected by the Barratt Impulsiveness Scale (BIS-11), are distinctly associated with cortical thickness and surface area variations in young healthy individuals.MethodWe investigated cortical thickness and surface area in 54 healthy volunteers (m/f = 30%/70%; age mean/SD = 24.9/4.02) using structural magnetic resonance imaging at 3 T together with surface-based analysis techniques. Impulsivity was examined on the Barratt impulsiveness scale (BIS-11) and related to the two distinct cortical measurements.ResultsHigher BIS-11 total scores were negatively associated with cortical thickness variations in the left lingual gyrus, left superior temporal gyrus, right cuneus, and right superior parietal gyrus (p < 0.05 cluster-wise probability [CWP] corrected). Higher BIS-11 nonplanning scores were negatively associated with cortical thickness variations in bilateral pericalcarine gyrus (p < 0.05 CWP corr.). In the orbitofrontal cortex, the association between impulsivity and cortical thickness differed significantly between males and females.ConclusionThese data suggest distinct neurodevelopmental trajectories underlying impulsivity in healthy subjects. Impulsivity total scores appear to be specifically related to cortical thickness variations, in contrast to variations of cortical surface area. Furthermore, our findings underscore the importance of better characterizing gender-specific structural correlates of impulsivity.
https://ift.tt/2kpua0b
The homing of human umbilical cord-derived mesenchymal stem cells and the subsequent modulation of macrophage polarization in type 2 diabetic mice
Source:International Immunopharmacology, Volume 60
Author(s): Yaqi Yin, Haojie Hao, Yu Cheng, Jieqing Gao, Jiejie Liu, Zongyan Xie, Qi Zhang, Li Zang, Weidong Han, Yiming Mu
Umbilical cord-derived mesenchymal stem cells (UC-MSCs), with both immunomodulatory and pro-regenerative properties, are promising for the treatment of type 2 diabetes mellitus (T2DM). As efficient cell therapy largely relies on appropriate homing to target tissues, knowing where and to what extent injected UC-MSCs have homed is critically important. However, bio-distribution data for UC-MSCs in T2DM subjects are extremely limited. Beneficial effects of UC-MSCs on T2DM subjects are associated with increased M2 macrophages, but no systemic evaluation of M2 macrophages has been performed in T2DM individuals. In this study, we treated T2DM mice with CM-Dil-labelled UC-MSCs. UC-MSC infusion not only exerted anti-diabetic effects but also alleviated dyslipidemia and improved liver function in T2DM mice. To compare UC-MSC migration between T2DM and normal subjects, a collection of normal mice also received UC-MSC transplantation. UC-MSCs homed to the lung, liver and spleen in both normal and T2DM recipients. Specifically, the spleen harbored the largest number of UC-MSCs. Unlike normal mice, a certain number of UC-MSCs also homed to pancreatic islets in T2DM mice, which suggested that UC-MSC homing may be closely related to tissue damage. Moreover, the number of M2 macrophages in the islets, liver, fat and muscle significantly increased after UC-MSC infusion, which implied a strong link between the increased M2 macrophages and the improved condition in T2DM mice. Additionally, an M2 macrophage increase was also observed in the spleen, suggesting that UC-MSCs might exert systemic effects in T2DM individuals by modulating macrophages in immune organs.
https://ift.tt/2xdpT9n
IL-9 exhibits elevated expression in osteonecrosis of femoral head patients and promotes cartilage degradation through activation of JAK-STAT signaling in vitro
Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Wei Geng, Wen Zhang, Jinzhu Ma
Osteonecrosis of the femoral head (ONFH) often causes severe symptoms in young people and limits the mobility of the hip joint. Interleukin-9 (IL-9) is a multi-functional inflammatory factor that participates in lumbar disk herniation and arthritis and has been reported in many studies. However, the correlation between IL-9 and ONFH is unclear. The present study aimed to determine the role of IL-9 in the pathogenetic mechanism of osteonecrosis. To assess IL-9 expression in ONFH and femoral neck fracture patients, cartilage tissue was examined through western blot analysis and immunohistochemistry. Human primary chondrocytes were stimulated with IL-9, and inflammation-related cytokines and cartilage matrix-degrading enzymes were assessed via real-time PCR. After being treated with IL-9, Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling were tested through western blot analysis. Our results showed a significant increase in the expression of IL-9 in ONFH patients. IL-9 raised the level of inflammation-related cytokines and cartilage matrix-degrading enzymes and enhanced the activation of JAK-STAT signaling. Furthermore, blocking the JAK-STAT signaling pathway reduced the secretion of inflammation-related cytokines and cartilage matrix-degrading enzymes and markedly alleviated the degradation of the cartilage matrix. These findings provide new insights into the role that IL-9 plays in the pathogenetic mechanism of osteonecrosis and also provide a potential treatment for ONFH.
Graphical abstract
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Enhancing the effects of chemotherapy by combined macrophage-mediated photothermal therapy (PTT) and photochemical internalization (PCI)
Abstract
Light-based treatment modalities such as photothermal therapy (PTT) or photochemical internalization (PCI) have been well documented both experimentally and clinically to enhance the efficacy of chemotherapy. The main purpose of this study was to examine the cytotoxic effects of silica–gold nanoshell (AuNS)-loaded macrophage-mediated (MaNS) PTT and bleomycin BLM-PCI on monolayers of squamous cell carcinoma cells. The two modalities were applied separately and in simultaneous combination. Two different wavelengths of light were employed simultaneously, one to activate a highly efficient PCI photosensitizer, AlPcS2a (670 nm) and the other for the MaNS-mediated PTT (810 nm), to evaluate the combined effects of these modalities. The results clearly demonstrated that macrophages could ingest sufficient numbers of silica–gold nanoshells for efficient near infrared (NIR) activated PTT. A significant synergistic effect of simultaneously applied combined PTT and PCI, compared to each modality applied separately, was achieved. Light-driven therapies have the advantage of site specificity, non-invasive and non-toxic application, require inexpensive equipment and can be given as repetitive treatment protocols.
https://ift.tt/2IP9X2o
Long-term (2005–2015) trend analysis of PM 2.5 precursor gas NO 2 and SO 2 concentrations in Taiwan
Abstract
Ground air monitoring stations have been installed in Taiwan since 1993 to ensure whether the criteria air pollutants meet the ambient air quality standards. In the present study, the data from the monitoring stations were used to evaluate long-term (2005–2015) trend of NO2 and SO2 in three metropolitan cities (northern Taipei, central Taichung, and southern Kaohsiung), two eastern coastal cities (Hualien and Taitung), and one agricultural city in west-central plain (Douliu); those cities essentially covered the entire region of Taiwan. The results indicate that SO2 and NO2 concentrations of all studied six cities meet the annual average standards of 30 and 50 ppb, respectively. After deseasonalizing the original data and using 7-month moving average, the trend analysis reveals a decreasing trend ranging from 0.15 to 0.57 ppb/year (R2 from 0.33 to 0.85) for NO2 and 0.06 to 0.45 ppb/year (R2 from 0.32 to 0.92) for SO2; the corresponding reductions over the 10-year span are 4 to 42% for NO2 and 22 to 52% for SO2. The reduction trend, despite the growth in GDP, vehicle numbers and energy consumption, industrial output, etc., is similar to those of developed countries. Clearly, there are seasonal/monthly variation patterns for these two precursor gases with minimum levels in summer (July) and maximum in winter (December). The concentration reductions, however, were lagging behind the respective emission reductions. There are significant correlations among six cites for NO2 (r = 0.58–0.93) and, to some extent, SO2 (0.32–0.66). The correlation between SO2 and NO2 (r = 0.46–0.74) indicates same or similar emission sources. Furthermore, the correlation between observed pollutant concentrations and their emission is excellent for SO2 in two cities (0.79–0.96). The SO2/NO2 ratios vary with city and time and the value is site specific. For example, in 2005, the SO2/NO2 ratio was 0.38 in Kaohsiung and 0.18 in both Taipei and Taichung, the latter reflecting significant contribution from mobile sources. However, they all converged to 0.18–0.28 in 2015 in the six cities evaluated. All in all, the policies/measures made by the central and local government are effective in reducing ambient SO2 and NO2 levels.
https://ift.tt/2koK3nw
Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action
AbstractImmune checkpoint inhibitors (ICIs) have transformed the treatment landscape for cancer. Due to the mechanism of action of ICIs, inflammatory reactions against normal tissue were an anticipated side effect of these agents; these immune‐related adverse events have been documented and are typically low grade and manageable. Myocarditis has emerged as an uncommon but potentially life‐threatening adverse reaction in patients treated with ICIs. Assessment and characterization of ICI‐associated myocarditis is challenging because of its low incidence and protean manifestations. Nevertheless, the seriousness of ICI‐associated myocarditis justifies a coordinated effort to increase awareness of this syndrome, identify patients who may be at risk, and enable early diagnosis and appropriate treatment. The "Checkpoint Inhibitor Safety Working Group," a multidisciplinary committee of academic, industry, and regulatory partners, convened at a workshop hosted by Project Data Sphere, LLC, on December 15, 2017. This meeting aimed to evaluate the current information on ICI‐associated myocarditis, determine methods to collect and share data on this adverse reaction, and establish task forces to close the identified knowledge gaps. In this report, we summarize the workshop findings and proposed steps to address the impact of ICI‐associated myocarditis in patients with cancer.
https://ift.tt/2saP7PS
Association Between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer
AbstractBackground.Folate level was proposed to be a predictor for fluoropyrimidine‐related toxicity. We conducted a prospective study to determine the association between serum and red‐cell folate and capecitabine‐related toxicity in patients with colorectal cancers.Materials and Methods.Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine‐oxaliplatin (CAPOX) for adjuvant or palliative purposes. Exclusion criteria included concomitant radiotherapy or chemotherapy other than capecitabine or CAPOX and creatinine clearance <30 mL/min. Fasting serum and red‐cell folate were measured prior to chemotherapy. Capecitabine was administered at 2,500 mg/m2 per day (monotherapy) or 2,000 mg/m2 per day (CAPOX) for 14 days every 3 weeks. The toxicity of the first four cycles was documented by clinical investigators who were blinded to folate levels.Results.A total of 144 patients were recruited, of whom 126 were eligible; 40 patients had capecitabine alone, and 86 patients received CAPOX. The rates of grade 2 and grade 3 toxicity were 63.5% and 14.3%, respectively. Nausea and vomiting were the most common grade ≥2 adverse event (47.7%), followed by hand‐foot syndrome (25.4%), diarrhea (23.1%), and neutropenia (22.3%). Combination with oxaliplatin (odds ratio [OR], 2.77; p = .043) and serum folate (OR, 10.33; p = .002) were independent predictors of grade ≥2 toxicity. Red‐cell folate was not predictive of toxicity. For every 10 nmol/L increment in serum folate, the risk of grade ≥2 toxicity increased by 9%.Conclusion.Serum folate level, but not red‐cell folate, was associated with higher rate of grade ≥2 toxicity during capecitabine‐based treatment. Excessive folate intake may be avoided before and during capecitabine‐based chemotherapy. The Oncologist 2018;23:1–10
https://ift.tt/2kuU6rb
Immune Checkpoint Inhibitor‐Associated Myocarditis
AbstractImmune checkpoint inhibitors (ICIs) are approved for a wide range of malignancies. They work by priming the immune system response to cancer and have changed the landscape of available cancer treatments. As anticipated, modulation of the regulatory controls in the immune system with ICIs results in diverse immune‐related adverse events, targeting any organ or gland. These toxicities are rarely fatal and generally regress after treatment discontinuation and/or prescription of corticosteroids. Recently, several cases of ICI‐related cardiotoxicity have been reported with complications ranging from cardiogenic shock to sudden death. The true incidence of ICI‐associated myocarditis is likely underestimated, due to a combination of factors including the lack of specificity in the clinical presentation, the potential of overlap with other cardiovascular and general medical illnesses, the challenges in the diagnosis, and a general lack of awareness of this condition. Currently, there are no clear guidelines for surveillance, diagnosis, or management of this entity. There are multiple unresolved issues including, but not limited to, identifying those at risk of this uncommon toxicity, elucidating the pathophysiology, determining if and what type of surveillance is appropriate, optimal work‐up of suspected patients, and methods for resolution of myocarditis. Here we describe a clinical vignette and discuss the salient features and management strategies of ICI‐associated myocarditis. The Oncologist 2018
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Targeted Alpha Therapy using Radium-223: From physics to biological effects
Source:Cancer Treatment Reviews
Author(s): I.A. Marques, A.R. Neves, A.M. Abrantes, A.S. Pires, E. Tavares-da-Silva, A. Figueiredo, M.F. Botelho
With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 (223Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical.
https://ift.tt/2J8HrZ3
Restoration with pioneer plants changes soil properties and remodels the diversity and structure of bacterial communities in rhizosphere and bulk soil of copper mine tailings in Jiangxi Province, China
Abstract
To unravel the ecological function played by pioneer plants in the practical restoration of mine tailings, it is vital to explore changes of soil characteristics and microbial communities in rhizosphere and bulk soil following the adaptation and survival of plants. In the present study, the diversity and structure of rhizospheric bacterial communities of three pioneer plants in copper mine tailings were investigated by Illumina MiSeq sequencing, and the effects of pioneer plants on soil properties were also evaluated. Significant soil improvement was detected in rhizospheric samples, and Alnus cremastogyne showed higher total organic matter, total nitrogen, and available phosphorus than two other herbaceous plants. Microbial diversity indices in rhizosphere and bulk soil of reclaimed tailings were significantly higher than bare tailings, even the soil properties of bulk soil in reclaimed tailings were not significantly different from those of bare tailings. A detailed taxonomic composition analysis demonstrated that Alphaproteobacteria and Deltaproteobacteria, Chloroflexi, Acidobacteria, and Gemmatimonadetes showed significantly higher relative abundance in rhizosphere and bulk soil. In contrast, Gammaproteobacteria and Firmicutes were abundant in bare tailings, in which Bacillus, Pseudomonas, and Lactococcus made up the majority of the bacterial community (63.04%). Many species within known heavy metal resistance and nutrient regulatory microorganism were identified in reclaimed tailings, and were more abundant among rhizospheric microbes. Hierarchical clustering and principal coordinate analysis (PCoA) analysis demonstrated that the bacterial profiles in the rhizosphere clustered strictly together according to plant types, and were distinguishable from bulk soil. However, we also identified a large shared OTUs that occurred repeatedly and was unaffected by highly diverse soil properties in rhizosphere and bulk samples. Redundancy analysis indicated that water content and Cu and As concentrations were the main environmental regulators of microbial composition. These results suggest that the interactive effect of pioneer plants and harsh soil environmental conditions remodel the specific bacterial communities in rhizosphere and bulk soil in mine tailings. And A. cremastogyne might be approximate candidate for phytoremediation of mine tailings for better soil amelioration effect and relative higher diversity of bacterial community in rhizosphere.
https://ift.tt/2s96W2Q
Application of blueberry anthocyanins reduces perfluorooctane sulfonate toxicity on planarians ( Dugesia japonica ) in locomotion, regeneration, and gene expression and contents
Abstract
Perfluorooctane sulfonate (PFOS) which has been distributed worldwide is a persistent organic contaminant. Blueberry anthocyanins (ANT) are phytonutrients with antioxidant activities. The influence of different PFOS and ANT concentrations on the behavioral activities, regeneration of planarians (Dugesia japonica), and the expression levels and contents of Djnad6 and Djcox1 genes has been investigated. PFOS treatments affected the gene expression levels, induced a decrease in the planarians' locomotor velocity, and increased the time required for the regeneration of the transverse amputated fragments in a time- and dose-dependent manner. Additionally, ANT treatments, to a certain extent, alleviated the damage caused by PFOS to planarians. ANT increased the planarians' locomotor velocity and the percentage of regenerating planarians with eyespots and auricles. Furthermore, ANT alleviated the expression disorders of Djnad6 and Djcox1 induced by PFOS.
https://ift.tt/2xaHYoF
Green solid synthesis of polyaniline-silver oxide nanocomposite for the adsorptive removal of ionic divalent species of Zn/Co and their radioactive isotopes 65 Zn/ 60 Co
Abstract
A comparative study between two nanosorbents, nanopolyaniline (NPANI) and nanopolyaniline coated with nanosilver oxide (NPANI-NAg2O) is explored to dispose the divalent species of Zn/Co from water and radioactive isotopes 65Zn/60Co from radioactive wastewater using batch and column techniques. NPANI-NAg2O nanocomposite was synthesized via solid-solid reaction. Characterization was achieved using FT-IR, TGA, XRD, SEM, HR-TEM, and surface area analysis. The images of SEM and HR-TEM confirmed the success of the modification process and the particle size was found in the range 28.78–68.28 nm (NPANI) and 25.74–85.71 nm (NPANI-NAg2O), respectively. Solution pH, contact time, solid dosage, and ionic concentration of the metals were studied as fundamental factors. The obtained results indicated that the optimum conditions to dispose Zn/Co divalent species using NPANI were pH 7 and 30–33 min, while NPANI-NAg2O exhibited the optimum conditions at pH 7 and 20–30 min. The maximum removal capacities were 100.1 and 139.75 mg/g for Zn(II) and 57.93 and 112.1 mg/g for Co(II) using NPANI and NPANI-NAg2O, respectively.
Graphical abstract
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https://ift.tt/2s9I2jr
Efficiency of biomonitoring methods applying tropical bioindicator plants for assessing the phytoxicity of the air pollutants in SE, Brazil
Abstract
In the tropical region, the greatest challenge of the biomonitoring approach is to establish linear relationships between biomarkers measured in plants and pollutant concentrations, since the bioindicator responses can be intensified or restricted by climatic variations. In southeastern Brazil, there are two regions affected by air pollution, where the Atlantic Forest remains and should be preserved. Consequently, both areas have been monitored by biomonitoring procedures using standardized and tropical plants. The industrial complex settled in Cubatão is one of the world's most famous examples of environmental pollution and degradation, with consequent decline of the Atlantic Forest. An oil refinery is among the most polluting industries in the Cubatão region. The other region is located in the Metropolitan Region of Campinas (MRC). The MRC has been affected by high levels of air pollutants originated from road traffic and is responsible for over 80% of CO, NOx, and hydrocarbon emissions and develops industrial activities that emit about 70% of the particulate matter present in the region. Both regions are distinguished by the climate, despite the fact that they are only about 130 km far from each other. Several studies carried out by our group in these regions aimed to establish the best native tree species and respective potential biomarkers for future assessment of pollution effects on tropical Forests. We present a critical review about the efficiency of native species compared to standardized bioindicator plants considering antioxidant defense system, nutrient accumulation, and microscopic aspects when exposed to atmospheric pollutants and climate.
https://ift.tt/2xaHPS9
The role of depressive symptoms in treatment of adolescent cannabis use disorder with N-Acetylcysteine
Source:Addictive Behaviors, Volume 85
Author(s): Rachel L. Tomko, Amanda K. Gilmore, Kevin M. Gray
Relative to adults, adolescents are at greater risk of developing a cannabis use disorder (CUD) and risk may be exacerbated by co-occurring depressive symptoms. N-Acetylcysteine (NAC), an over-the-counter antioxidant, is thought to normalize glutamate transmission. Oxidative stress and glutamate transmission are disrupted in both depression and CUD. Thus, NAC may be particularly effective at promoting cannabis abstinence among adolescents with elevated depressive symptoms. Secondary analyses were conducted using a sub-sample of adolescents with CUD (N = 74) who participated in an 8-week randomized placebo-controlled clinical trial examining the efficacy of NAC for cannabis cessation. It was hypothesized that NAC would reduce severity of depressive symptoms, and that decreases depressive symptom severity would mediate decreases in positive weekly urine cannabinoid tests (11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Additionally, it was expected that adolescents with greater severity of baseline depressive symptoms would be more likely to become abstinent when assigned NAC relative to placebo. Results from linear mixed models and generalized estimating equations did not suggest that NAC reduced severity of depressive symptoms, and the hypothesis that NAC's effect on cannabis cessation would be mediated by reduced depressive symptoms was not supported. However, an interaction between treatment condition and baseline severity of depressive symptoms as a predictor of weekly urine cannabinoid tests was significant, suggesting that NAC was more effective at promoting abstinence among adolescents with heightened baseline depressive symptoms. These secondary findings, though preliminary, suggest a need for further examination of the role of depressive symptoms in treatment of adolescent CUD with NAC.
https://ift.tt/2GQJNqi
Collecting outcome data of a text messaging smoking cessation intervention with in-program text assessments: How reliable are the results?
Source:Addictive Behaviors, Volume 85
Author(s): Johannes Thrul, Judith A. Mendel, Samuel J. Simmens, Lorien C. Abroms
BackgroundText messaging interventions have shown promise in helping people quit smoking. Texting programs periodically survey participants about their smoking status. This study examined the consistency of participant self-reported smoking between external surveys and internal program text message assessments.MethodsParticipants in Text2Quit program were surveyed about their past 7-day smoking at one, three, and six months post-enrollment using different survey modes (external surveys and internal program text message assessments) and responses were compared for consistency. The first set of analyses was conducted for participants responding on both modes (n = 45 at one month; n = 50 at three months; n = 42 at six months). Additional analyses, assuming missing = smoking, were conducted with the full sample of 262 smokers (68.7% female, mean age = 35.8 years) and compared to saliva-confirmed abstinence rates.ResultsParticipants responding to both modes consistently reported smoking status at one (88.9%), three (88.0%) and six (88.1%) months post-enrollment, with fair to substantial levels of agreement (one month: κ = 0.24; three months: κ = 0.63; six months: κ = 0.66). Participants responding to both modes reported high rates of abstinence. In missing = smoking analyses, significant differences in abstinence rates reported across modes were detected at each timepoint (one month: external = 30.5%, internal = 16.4%; three months: external = 33.2%, internal = 16.0%; six months: external = 31.7%, internal = 12.2%; all p < .001). Moderate levels of agreement were found between the two modes. At 6 months, abstinence rates obtained via internal data were closer to those biochemically verified (15.7%) compared to external surveys.ConclusionsResults provide initial support for the use of internal program assessments in text messaging programs with missing = smoking assumptions in order to gather outcome data on smoking behavior.
https://ift.tt/2INNXoI
Extraversion, neuroticism, and the electrocortical response to monetary rewards in adolescent girls
Source:Biological Psychology
Author(s): Brittany C. Speed, Brady D. Nelson, Amanda R. Levinson, Greg Perlman, Daniel N. Klein, Roman Kotov, Greg Hajcak
Affective personality traits, such as extraversion and neuroticism, are associated with individual differences in reward system functioning. The reward positivity (ΔRewP) is an event-related potential (ERP) component that indexes sensitivity to reward, and can be elicited by feedback indicating monetary gains relative to losses. In a sample of 508 adolescent girls, the current study examined the relationship between extraversion, neuroticism, and their respective facets and the ΔRewP. Results indicated an Extraversion × Neuroticism interaction, such that greater extraversion was associated with an increased ΔRewP, but only in the context of low neuroticism. This association was primarily due to the extraversion facet positive emotionality—high levels of positive emotionality were associated with an increased ΔRewP, but only in the context of low neuroticism. In addition, increased neuroticism diminished the age-related increase in the ΔRewP. The current study suggests that both extraversion and neuroticism are associated with reward system function in adolescence.
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État scléreux révélant une porphyrie cutanée tardive
Publication date: Available online 24 May 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Brunet, E. Hainaut
IntroductionLa porphyrie cutanée tardive (PCT) de type 1 est liée à une accumulation cutanée de porphyrines. Cette accumulation est due à un déficit en uroporphyrinogène décarboxylase strictement limité aux hépatocytes. Classiquement, elle se manifeste par une éruption bulleuse photo-distribuée.ObservationUne femme de 59 ans se présentait à la consultation de dermatologie pour des lésions scléreuses qui évoluaient depuis un an. Le reste de l'examen clinique et les explorations complémentaires n'orientaient pas vers une sclérodermie systémique. Le caractère photo-distribué des lésions conduisait à réaliser un dosage des porphyrines urinaires, qui étaient très élevées. Le taux sanguin d'uroporphyrinogène décarboxylase était en revanche normal, confirmant le diagnostic de PCT de type 1. La recherche d'une cause hépatique permettait de mettre en évidence une mutation hétérozygote H63D/C282Y du gène de l'hémochromatose. La patiente bénéficiait de saignées régulières, permettant une disparition complète de la sclérose cutanée.DiscussionLes lésions sclérodermiformes sont un mode de présentation inhabituel de la PCT, à l'origine de retards diagnostiques. L'accumulation d'uroporphyrines au niveau du derme stimulerait les fibroblastes, qui par la suite, synthétiseraient du collagène, expliquant la sclérose cutanée.BackgroundPorphyria cutanea tarda (PCT) is associated with cutaneous accumulation of porphyrins. This accumulation results from a deficiency of uroporphyrinogen decarboxylase occurring only in the liver. The classical presentation is blistering on sun-exposed areas.Patients and methodsA 59-year-old woman presented at the dermatology consultation for sclerotic lesions that had been present for one year. The remainder of the clinical examination and further investigations did not indicate systemic scleroderma. The sun-exposed nature of the lesions led us to perform an assay of urinary porphyrin, which was found to be elevated. Uroporphyrinogen decarboxylase levels were normal, confirming the diagnosis of type 1 PCT. Screening for a hepatic etiology revealed a heterozygous mutation H63D/C282Y of the hemochromatosis gene responsible for this clinical picture. The patient underwent regular bleeding, which led to complete disappearance of cutaneous sclerosis.DiscussionSclerodermatous lesions are an unusual presentation of PCT and cause delays in diagnosis. The accumulation of uroporphyrins in the dermis stimulates fibroblasts, which then synthesize collagen, resulting in cutaneous sclerosis.
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Globular amyloidosis of the colon
Publication date: Available online 24 May 2018
Source:Arab Journal of Gastroenterology
Author(s): C. Díaz del Arco, M.J. Fernández Aceñero
Gastrointestinal involvement is frequent in systemic amyloidosis. However, amyloidosis can rarely be confined to the gastrointestinal tract or appear as a tumour mass. There have been few reports describing amyloid globular deposits in a variety of locations, as opposed to the usual linear ones. We herein report a rare case of globular amyloidosis involving the large bowel, which to the best of our knowledge is the second reported in the world literature.A 74-year-old man consulted on anaemia. Endoscopy showed ulcerative lesions in the left colon, which were biopsied and diagnosed as ischemic colitis. Under light microscopy, we found globular discrete deposits in the lamina propria which were Congo red-positive and resistant to permanganate digestion. Histopathological diagnosis was globular amyloidosis with AL deposits. The patient underwent further studies, including a haematologic evaluation that discarded systemic involvement.Globular amyloidosis seems to be a rare morphologic type of amyloidosis, but not a distinct entity. Its etiology, pathogenesis and relationship with patient prognosis and disease severity remain largely unknown. When amyloid deposits are confined to the gastrointestinal tract, systemic therapy can be avoided and patients should only be followed periodically. Immunohistochemical classification and clinical correlation are essential to rule out systemic amyloidosis.
https://ift.tt/2IJUYXE
Retrospective self-sorted 4D-MRI for the liver
Source:Radiotherapy and Oncology
Author(s): Tessa N. van de Lindt, Martin F. Fast, Uulke A. van der Heide, Jan-Jakob Sonke
PurposeDaily MRI-guidance for liver radiotherapy is becoming possible on an MR-Linac. The purpose of this study was to develop a 4D-MRI strategy using an image-based respiratory signal with an acquisition-reconstruction time <5 min, providing T2-weighting for non-contrast enhanced tumor visibility.Materials and MethodsImages were acquired using an axial multi-slice 2D Turbo Spin Echo (TSE) sequence, repeated a variable number of times (dynamics). A self-sorting signal (SsS) was retrieved from the data by computing correlation coefficients between all acquired slices. Images were sorted into 10 phases and missing data were interpolated. The method was validated in a phantom and 10 healthy volunteers. The SsS, image quality (SSIM index: structural similarity index) and quantified liver motion were assessed as a function of the number of dynamics. Tumor visibility was demonstrated in two patients with liver metastasis on the Elekta Unity MR-Linac.ResultsSsS was in good agreement with the reference navigator signal. Missing data increased from 0.4 ± 0.6% to 37.1 ± 6.6% for 60 to 10 dynamics. The SSIM index for the interpolated slices was ∼0.6. The RMSD of quantified motion was <1 mm in phantom experiments and in volunteers <1 mm for >10 dynamics.ConclusionFor 30 dynamics, acquisition-reconstruction time was <5 min and showed good performance in the validation experiments. The tumor was clearly visible in the patient images.
https://ift.tt/2INwSHB
Art is long, life is short. Francisco José de Goya y Lucientes (1746–1828), the suffering artist
Source:Medical Hypotheses
Author(s): Gabriele Cipriani, Luca Cipriani, Lucia Picchi, Mario Di Fiorino
Francisco José de Goya y Lucientes is one of the major figures of European art. From royal portraits to bizarre, grotesque illustrations, his legacy demonstrates a tortured genius, generating some of the most compelling art ever produced. His story is also the story of Spain during one of the most tumultuous passages of its history. In the winter of 1792–3, Goya experienced a mysterious illness resulting in lifelong deafness. After that, his work became more negative, with thick, bold strokes of dark colour. Scholars have suggested various diagnoses on the basis of Master's symptoms, but the exact nature of the illness has never been identified.
https://ift.tt/2scTcDf
Can you use Botox under your eyes?
Botox is often used to treat lines and wrinkles around the eyes and mouth. Can it also reduce dark circles or bags under the eyes? Using Botox under the eyes is not approved in the U.S. and researchers are unsure how well it may work and what side effects may occur. Here, learn about the procedure and its alternatives.
https://ift.tt/2KVnoKK
Challenges for the registration of vaccines in emerging countries: Differences in dossier requirements, application and evaluation processes
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Nora Dellepiane, Sonia Pagliusi
The divergence of regulatory requirements and processes in developing and emerging countries contributes to hamper vaccines' registration, and therefore delay access to high-quality, safe and efficacious vaccines for their respective populations. This report focuses on providing insights on the heterogeneity of registration requirements in terms of numbering structure and overall content of dossiers for marketing authorisation applications for vaccines in different areas of the world. While it also illustrates the divergence of regulatory processes in general, as well as the need to avoid redundant reviews, it does not claim to provide a comprehensive view of all processes nor existing facilitating mechanisms, nor is it intended to touch upon the differences in assessments made by different regulatory authorities. This report describes the work analysed by regulatory experts from vaccine manufacturing companies during a meeting held in Geneva in May 2017, in identifying and quantifying differences in the requirements for vaccine registration in three aspects for comparison: the dossier numbering structure and contents, the application forms, and the evaluation procedures, in different countries and regions. The Module 1 of the Common Technical Document (CTD) of 10 countries were compared. Modules 2–5 of the CTDs of two regions and three countries were compared to the CTD of the US FDA. The application forms of eight countries were compared and the registration procedures of 134 importing countries were compared as well. The analysis indicates a high degree of divergence in numbering structure and content requirements. Possible interventions that would lead to significant improvements in registration efficiency include alignment in CTD numbering structure, a standardised model-application form, and better convergence of evaluation procedures.
https://ift.tt/2J6vt24
WHO/IVI global stakeholder consultation on group A Streptococcus vaccine development: Report from a meeting held on 12–13 December 2016
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Joshua Osowicki, Johan Vekemans, David C. Kaslow, Martin H. Friede, Jerome H. Kim, Andrew C. Steer
While progress towards a Group A Streptococcus (GAS) vaccine has been stalled by a combination of scientific, regulatory, and commercial barriers, the problem persists. The high and globally-distributed burden of disease attributable to GAS makes vaccination an imperative global public health goal. Advances across a range of scientific disciplines in understanding GAS diseases have made the goal a realistic one and focused attention on the need for coordinated global action. With a view to accelerating GAS vaccine development, the World Health Organization (WHO) and the International Vaccine Institute (IVI) convened a global stakeholder consultation on the 12th and 13th of December 2016, in Seoul, South Korea. Topics discussed included: (1) gaps in current knowledge of global GAS epidemiology, burden of disease, and molecular epidemiology; (2) contribution of pre-clinical models to candidate vaccine evaluation and new immunological assays to address GAS immunology knowledge gaps; (3) status and future of the GAS vaccine development pipeline; and (4) defining a pathway to licensure, policy recommendations and availability of a vaccine. The meeting determined to establish a GAS vaccine working group to coordinate preparation of a global vaccine values proposition, preferred product characteristics, and a technical research and development roadmap. A new global GAS vaccine consortium will drive strategic planning to anticipate requirements for licensure, prequalification, and policy recommendations.
https://ift.tt/2GTeJq8
Selecting the right indicators to ensure optimised implementation of BCG vaccination policy
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Sanne Marie Thysen, Ane Bærent Fisker
https://ift.tt/2kpOPkJ
BCG vaccine: WHO position paper, February 2018 – Recommendations
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): World Health Organization
This article presented the World Health Organization's (WHO) recommendations on the use of on Bacille Calmette-Guérin (BCG) vaccine excerpted from the BCG vaccines: WHO position paper – February 2018 published in the Weekly Epidemiological Record [1]. This position paper replaces the 2004 WHO position paper on Bacille Calmette-Guérin (BCG) vaccine [2] and the 2007 WHO revised BCG vaccination guidelines for infants at risk for human immunodeficiency virus (HIV) infection [3]. It incorporates recent developments in the tuberculosis (TB) field, provides revised guidance on the immunization of children infected with HIV, and re-emphasizes the importance of the birth dose. This position paper also includes recommendations for the prevention of leprosy.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation tables. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of cholera vaccines were discussed by the Strategic Advisory Group of Experts (SAGE) in October 2017; evidence presented at these meetings can be accessed at: https://ift.tt/2GT06qS
https://ift.tt/2sefp3O
Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Kirsten S. Vannice, Annelies Wilder-Smith, Alan D.T. Barrett, Kalinka Carrijo, Marco Cavaleri, Aravinda de Silva, Anna P. Durbin, Tim Endy, Eva Harris, Bruce L. Innis, Leah C. Katzelnick, Peter G. Smith, Wellington Sun, Stephen J. Thomas, Joachim Hombach
Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines.
https://ift.tt/2sbH8SQ
Editorial Board/Aims and Scope
Source:Vaccine, Volume 36, Issue 24
https://ift.tt/2J9PDIz
Cholera vaccine: WHO position paper, August 2017 – Recommendations
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): World Health Organization
This article presents the World Health Organization's (WHO) recommendations on the use of cholera vaccines excerpted from the Cholera vaccines: WHO position paper, August 2017, published in the Weekly Epidemiological Record (Cholera vaccine, 2017) [1]. This position paper replaces the 2010 WHO position paper on cholera vaccines (Cholera vaccine, 2010) [2]. It incorporates the most recent evidence on cholera vaccination and provides revised recommendations on the target populations for cholera immunization.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of cholera vaccines were discussed by the Strategic Advisory Group of Experts (SAGE) in April 2017; evidence presented at these meetings can be accessed at: https://ift.tt/2J9PogD.
https://ift.tt/2sb5qwh
Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Atsushi Komatsu, Shizunobu Igimi, Kei Kawana
Therapeutic HPV vaccine is an agent to induce E7-specific Th1 immune responses to treat cervical neoplasia (CIN2-3). Our previous clinical trial has demonstrated that oral administration of HPV16 E7-expressing Lactobacillus casei (L. casei), GLBL101c, resulted in the regression of HPV16-related CIN3. Here we examined optimization of the E7-expressing L. casei for induction of the mucosal immune responses to E7. Various doses of HPV16 E7 molecule were displayed on the L. casei. Immunization with E7-bound L. casei showed the induction of E7-specific mucosal IFNγ-producing cells was dependent on displayed E7-doses but saturated beyond 0.3 μg/108 cells. A new agent, L. casei with endogenous expression of E7 (IGMKK16E7), showed the optimal amount of displayed-E7. Immunization with IGMKK16E7 demonstrated 4-fold higher induction of E7-specific mucosal IFNγ-producing cells when compared with the former one. Our new system provided the optimal E7-expressing L. casei for displayed-E7 amount and induction of mucosal Th1 immune response.
https://ift.tt/2GS7PBc
Composition of gut microbiota and its influence on the immunogenicity of oral rotavirus vaccines
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Cliff A. Magwira, Maureen B. Taylor
The introduction of oral rotavirus vaccines (ORVVs) has led to a reduction in number of hospitalisations and deaths due to rotavirus (RV) infection. However, the efficacy of the vaccines has been varied with low-income countries showing significantly lower efficacy as compared to high-income countries. The reasons for the disparity are not fully understood but are thought to be multi-factorial. In this review article, we discuss the concept that the disparity in the efficacy of oral rotavirus vaccines between the higher and lower socio-economical countries could be due the nature of the bacteria that colonises and establishes in the gut early in life. We further discuss recent studies that has demonstrated significant correlations between the composition of the gut bacteria and the immunogenicity of oral vaccines, and their implications in the development of novel oral RV vaccines or redesigning the current ones for maximum impact.
https://ift.tt/2J31SXk
Does consecutive influenza vaccination reduce protection against influenza: A systematic review and meta-analysis
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Jessica J. Bartoszko, Isabella F. McNamara, Oguz A.Z. Aras, Danielle A. Hylton, Yuan B. Zhang, Danya Malhotra, Sarah L. Hyett, Rita E. Morassut, Paulina Rudziak, Mark Loeb
IntroductionVaccination against influenza on an annual basis is widely recommended, yet recent studies suggest consecutive vaccination may reduce vaccine effectiveness (VE).PurposeTo assess whether when examining the entirety of existing data consecutive influenza vaccination reduces VE compared to current season influenza vaccination.Data sourcesMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 26, 2017; citations of included studies.Study selectionRandomized, controlled trials (RCTs) and observational studies of children, adults and/or the elderly that reported laboratory-confirmed influenza infection over 2 or more consecutive influenza seasons were eligible.Data extractionData related to study characteristics, participant demographics, cases of influenza infection by vaccination group and risk of bias assessment was extracted in duplicate.Data synthesisFive RCTs involving 11,987 participants did not show a significant reduction in VE when participants vaccinated in two consecutive seasons (VE 71%, 95% CI 62–78%) were compared to those vaccinated in the current season (VE 58%, 95% CI 48–66%) (odds ratio [OR] 0.88, 95% CI 0.62–1.26, p = 0.49, I2 = 39%). Twenty-eight observational studies involving 28,627 participants also did not show a reduction (VE for two consecutive seasons 41%, 95% CI 30–51% compared to VE for current season 47%, 95% CI 39–54%; OR 1.14, 95% CI 0.98–1.32, p = 0.09, I2 = 63%). Results from subgroup analyses by influenza type/subtype, vaccine type, age, vaccine match and co-morbidity support these findings; however, dose–response results were inconsistent. Certainty in the evidence was assessed to be very low due to unexplained heterogeneity and imprecision.LimitationsThe inclusion of studies with relatively small sample sizes and low event rates contributed to the imprecision of summary VE and OR estimates, which were based on unadjusted data.ConclusionAvailable evidence does not support a reduction in VE with consecutive influenza vaccination, but the possibility of reduced effectiveness cannot be ruled out due to very low certainty in this evidence.Funding sourceCIHR Foundation Grant (PROSPERO: CRD42017059893).
https://ift.tt/2GQjeRX
The immunogenicity and protection effect of an inactivated coxsackievirus A6, A10, and A16 vaccine against hand, foot, and mouth disease
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Heeji Lim, Hyun Ju In, Jung-Ah Lee, Jung Sik Yoo, Sang-Won Lee, Gyung Tae Chung, Young Ki Choi, Jae Keun Chung, Sun Ju Cho, June-Woo Lee
Coxsackievirus belongs to the Enterovirus genus of the Picornaviridae family and is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD). Historically, outbreaks of HFMD have mainly been caused by enterovirus 71 and coxsackievirus A16. Recently, coxsackieviruses A6 and A10 have been associated with increased occurrences of sporadic HFMD cases and outbreak events globally. In this study, the immunogenicity of coxsackieviruses A6, A10, and A16 (CA6, CA10, and CA16), which were inactivated by formalin or β-propiolactone (BPL) under different conditions, was evaluated as multivalent vaccine candidates. CA6 induced similar immune responses with both inactivation methods, and the immune efficacy of CA10 and CA16 was better following inactivation with BPL than with formalin. There was no sufficient cross-reactivity or cross-protectivity against heterologous strains in groups vaccinated with the BPL-inactivated (BI) monovalent vaccine. Sufficient neutralizing antibody and cell-mediated immune responses were induced in the BI-trivalent vaccinated group. These findings suggest that BI-CA6, CA10, and CA16 are potential multivalent vaccine candidates and that a multivalent vaccine is needed to control HFMD. The coxsackievirus multivalent vaccine could be useful for the development of effective HFMD vaccines.
https://ift.tt/2krwx2N
Pharmacies versus doctors’ offices for adolescent vaccination
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Parth D. Shah, Macary W. Marciniak, Shelley D. Golden, Justin G. Trogdon, Carol E. Golin, Noel T. Brewer
PurposeWe sought to understand the relative advantage of pharmacies compared to doctors' offices for delivering HPV vaccination to adolescents.MethodsParticipants were a national sample of 1500 U.S. parents of adolescents ages 11–17 recruited in 2014–15. In an online survey, items informed by Diffusion of Innovation Theory assessed parents' perceptions of the relative advantages of HPV vaccine delivery in pharmacies and doctors' offices.Principle findingsMany parents believed doctor's offices offered a better health care environment than pharmacies, with more privacy (77%) and a safer place for vaccination (70%). However, many parents also believed pharmacies were more accessible than doctors' offices, requiring less time for vaccinations (71%) and offering more convenient hours (59%). Parents were more willing to get their children HPV vaccine from pharmacists if they indicated more relative advantages in vaccine delivery in pharmacies (β = .29; p < .001) and believed patient accessibility more important than health care environment (β = .20; p < .001).ConclusionsTo be more appealing to parents as HPV vaccine providers, pharmacy providers within community and hospital settings should build on their relative advantage with respect to accessibility and enhance their appeal of their healthcare environment.
https://ift.tt/2sdz8ko
Decreased accumulation of subgenomic RNA in human cells infected with vaccine candidate DEN4Δ30 increases viral susceptibility to type I interferon
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): José Bustos-Arriaga, Gregory D. Gromowski, Konstantin A. Tsetsarkin, Cai-Yen Firestone, Tannya Castro-Jiménez, Alexander G. Pletnev, Leticia Cedillo-Barrón, Stephen S. Whitehead
The NIH has developed live attenuated dengue virus (DENV) vaccine candidates by deletion of 30 nucleotides (Δ30) from the untranslated region of the viral genome. Although this attenuation strategy has proven to be effective in generating safe and immunogenic vaccine strains, the molecular mechanism of attenuation is largely unknown. To examine the mediators of the observed attenuation phenotype, differences in translation efficiency, genome replication, cytotoxicity, and type I interferon susceptibility were compared between wild type parental DENV and DENVΔ30 attenuated vaccine candidates. We observed that decreased accumulation of subgenomic RNA (sfRNA) from the vaccine candidates in infected human cells causes increased type I IFN susceptibility and propose this as one of the of attenuation mechanisms produced by the 3′ UTR Δ30 mutation.
https://ift.tt/2koOC1d
Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Seo-Yeon Jung, Kyung Won Kang, Eun-Young Lee, Dong-Won Seo, Hong-Lim Kim, Hak Kim, TaeWoo Kwon, Hye-Lim Park, Hun Kim, Sang-Myeong Lee, Jae-Hwan Nam
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime–boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime–boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime–boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime–boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime–boost regimens did not. Thus, heterologous prime–boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime–boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.
https://ift.tt/2GP1IxK
Influenza vaccine effectiveness in hospitalised Hong Kong children: Feasibility of estimates from routine surveillance data
Publication date: 7 June 2018
Source:Vaccine, Volume 36, Issue 24
Author(s): Karene Hoi Ting Yeung, Kate Ching Ching Chan, Paul K.S. Chan, David Shu Yan Lam, Philip Chak On Sham, Yat Sun Yau, Wai Hung Chan, Wa Keung Chiu, Kwok Leung Ng, Daniel Kwok Keung Ng, Iris Mei Ching Chan, E. Anthony S. Nelson
BackgroundHong Kong has a high burden of influenza hospitalisation. This study estimated influenza vaccine effectiveness in hospitalised Hong Kong children aged 6 months to below 6 years using data potentially obtainable from routine surveillance sources.MethodsThis 'test-negative' case-control study was conducted over two summer and one winter influenza seasons in five public Hong Kong hospitals during 2015 and 2016. Patients admitted for febrile and/or respiratory-associated illnesses who met inclusion criteria were invited to participate. Case-patients were respiratory-associated admissions with nasopharyngeal aspirate or nasopharyngeal swab specimens obtained during the first 48 h of hospitalisation that tested positive for influenza A or B, whereas control-patients were those with specimens that tested negative for both influenza A and B. Reliability of a routinely collected influenza immunisation status form was evaluated. Vaccine effectiveness for administration of full or partial series of influenza vaccination was calculated as 1 minus the odds ratio for influenza vaccination history for case-patients versus control-patients.Results2900 eligible subjects had influenza vaccination status available. A simple record form, designed to collect upon admission information on influenza vaccination status, was found to be reliable when compared to confirmed vaccination status from immunisation records and guardians' self-reports. Influenza vaccine effectiveness for preventing influenza A or B hospitalisation in children aged from 6 months to below 6 years during the period June 2015 to November 2016 was 68% (95% confidence interval [CI]: 55%, 77%) from unconditional analyses and 64% (95% CI: 46%, 75%) from conditional analyses.ConclusionsSeasonal influenza vaccine was effective in preventing hospitalisation from influenza A or B in young Hong Kong children during 2015 and 2016. As influenza vaccination status is not currently routinely recorded, implementation of an influenza immunisation status form in all paediatric wards, and centralising the data in Hong Kong's central computerised database, could provide real-time monitoring of influenza vaccine effectiveness.
https://ift.tt/2J88SCh
Association between provider recommendation and influenza vaccination status among children
Source:Vaccine, Volume 36, Issue 24
Author(s): Katherine E. Kahn, Tammy A. Santibanez, Yusheng Zhai, Carolyn B. Bridges
BackgroundProvider recommendation is associated with influenza vaccination receipt. The objectives of this study were to estimate the percentage of children 6 months–17 years for whom a provider recommendation for influenza vaccination was received, identify factors associated with receipt of provider recommendation, and evaluate the association between provider recommendation and influenza vaccination status among children.MethodsNational Immunization Survey-Flu (NIS-Flu) parentally reported data for the 2013–14, 2014–15, and 2015–16 seasons were analyzed. Tests of association between provider recommendation and demographic characteristics were conducted using Wald chi-square tests and pairwise comparison t-tests. Multivariable logistic regression was used to determine variables independently associated with receiving provider recommendation and the association between provider recommendation and influenza vaccination status.ResultsApproximately 70% of children had a parent report receiving a provider recommendation for influenza vaccination for their child. The strongest association between receipt of provider recommendation and demographic characteristics was with child's age, with younger children (6–23 months, 2–4 years, and 5–12 years) being more likely to have a provider recommendation than older children (13–17 years). In addition, children living in a household above poverty with household income >$75,000 were more likely to have a parent report receipt of a provider recommendation than children living below poverty. Children with a provider recommendation were twice as likely to be vaccinated than those without.ConclusionsThis study affirms the importance of provider recommendation for influenza vaccination among children. Ensuring that parents of all children receive a provider recommendation may improve vaccination coverage.
https://ift.tt/2sc1MSM
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