What can urban/rural differences in food allergy prevalence tell us about the drivers of food allergy?

Publication date: Available online 17 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Katrina J. Allen, Jennifer J. Koplin

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The Atopic March and Atopic Multimorbidity: Many Trajectories, Many Pathways

Publication date: Available online 17 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Amy S. Paller, Jonathan M. Spergel, Paola Mina-Osorio, Alan D. Irvine

Abstract

The "atopic march" recognizes the increased occurrence of asthma and/or allergic rhinitis after atopic dermatitis (AD) onset. Mechanisms for developing atopic comorbidities after AD onset are poorly understood, but may involve the impaired cutaneous barrier, which facilitates cutaneous sensitization. The association may also be driven or amplified in susceptible individuals by a systemic Th2-dominant immune response to cutaneous inflammation. However, these associations may merely involve shared genetic loci and environmental triggers, including microbiome dysregulation, with the temporal sequence reflecting tissue-specific peak time of occurrence of each disease, suggesting more of a clustering of disorders than a march. Prospective longitudinal cohort studies provide an opportunity to explore the relationships between post-dermatitis development of atopic disorders and potential predictive phenotypic, genotypic, and environmental factors. Recent investigations implicate disease severity and persistence, age of onset, parental atopic history, FLG (filaggrin) mutations, polysensitization, and the non-rural environment among risk factors for development of multiple atopic comorbidities in young children with AD. Early intervention studies to repair the epidermal barrier or alter exposure to the microbiome or allergens may elucidate the relative roles of barrier defects, genetic locus alterations, and environmental exposures in the risk and sequence of occurrence of Th2 activation disorders.

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IL-25 promotes Th2-type reactions and correlates with disease severity in the pathogenesis of oral lichen planus

Publication date: Available online 17 November 2018

Source: Archives of Oral Biology

Author(s): Hui Wang, Yuchen Jiang, Hongning Wang, Zhenhua Luo, Yuanyuan Wang, Xiaobing Guan

Abstract

Objective

The aim of the present study was to investigate the correlation between IL-25 expression and disease severity, and the potential immunoregulatory role of IL-25 expression in oral lichen planus (OLP).

Materials and Methods

The oral mucosal tissue samples obtained from OLP patients and healthy controls (HCs) were analyzed for IL-25 expression by real-time quantitative PCR (qPCR) and immunohistochemistry. Recombinant IL-25 was used to stimulate OLP patient-derived CD4 + T cells, and then IL-4 secretion and mRNA expression were evaluated by ELISA and qPCR, respectively. The efficiency of the siRNA-mediated knockdown of IL-25R expression in oral keratinocytes was determined by qPCR and Western blotting. Human oral keratinocyte cells were cultured with the recombinant human cytokines IL-25, IL-17 A and IL−17 F. The production of associated cytokines by keratinocytes was determined by qPCR. Statistical analyses of quantitative data were performed using SPSS software.

Results

The IL-25 and IL-4 mRNA levels were elevated and correlated significantly with each other in specific OLP subtype lesions compared to HCs, while the numbers of IL-25 positive cells were also increased in local OLP lesions as compared to HCs. In vitro culture with recombinant IL-25 could significantly promote CD4 + T cells from both subtypes of OLP to produce IL-4 mRNA and remarkably elevate supernatant IL-4 levels in reticular OLP CD4 + T cell cultures, which may be attributed to the elevated expression of IL-25R in local OLP lesions. Statistical analyses demonstrated that the simultaneously increased levels of IL-4, CXCL8 and CCL20 in keratinocytes were induced by IL-25 but not IL-17 A or IL−17 F. Decreasing IL-25R subunit expression by siRNA-mediated knockdown significantly blocked the expression of all cytokine-produced inflammatory mediators in oral keratinocytes.

Conclusions

In OLP lesions, IL-25 can function to mediate the Th2 response in specific disease subtypes, which may be an important cause of OLP disease chronicity and persistent inflammation.

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Forty cases of acquired oral syphilis and a review of the literature

Publication date: Available online 17 November 2018

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): L.F. Schuch, K.D. da Silva, J.A.A. de Arruda, A. Etges, A.P.N. Gomes, R.A. Mesquita, A.C.U. Vasconcelos, S.B.C. Tarquinio

Abstract

The aim of this study was to describe 40 cases of acquired oral syphilis (AOS) and to discuss the distribution of demographic characteristics, clinical features, and differential diagnosis of the disease. A retrospective study was conducted covering a 17-year period at a single institution in southern Brazil. Moreover, a literature review was performed through a search of the PubMed database for articles on AOS published between 1955 and March 2018. Data were analyzed descriptively. The predominant group within the case series was male patients in their twenties. The vast majority of cases (92.5%) were in the secondary stage of the disease. The lips were the most commonly affected site, with greyish-white mucous patches and reddish ulcers. In the literature review, the largest number of reported cases came from North America. Male patients in the third and fourth decades of life were most affected. AOS occurred more commonly as mucous patches and ulcers on the tongue and palate. Similarities regarding the distribution by sex, age, and anatomical location were found in the present study when compared to cases reported elsewhere. Clinicians, oral pathologists, and maxillofacial surgeons should familiarize themselves with the variable spectrum of signs and symptoms of AOS in their clinical practice to improve diagnosis and management.

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Three-dimensional soft tissue effects of mandibular midline distraction and surgically assisted rapid maxillary expansion: an automatic stereophotogrammetry landmarking analysis

Publication date: Available online 17 November 2018

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): A. Gül, M.A. de Jong, J.P. de Gijt, E.B. Wolvius, M. Kayser, S. Böhringer, M.J. Koudstaal

Abstract

Studies on mandibular midline distraction (MMD) are mostly performed using conventional research methods. Concerning surgically assisted rapid maxillary expansion (SARME), more research is conducted using three-dimensional (3D) techniques. Research on bimaxillary expansion, the combination of MMD and SARME, is reported sparsely. The main objective of this study was to provide a 3D evaluation of soft tissue effects following SARME and/or MMD. Patients who underwent SARME and/or MMD between 2008 and 2013 were included. Stereophotogrammetry was undertaken at the following time points: preoperative (T1), immediately post-distraction (T2), 1 year postoperative (T3). An automatic 3D facial landmarking algorithm using two-dimensional Gabor wavelets was applied for the analysis. Twenty patients who had undergone SARME were included, 12 of whom had undergone bimaxillary expansion. Age at the time of surgery ranged from 16 to 47 years. There was a significant downward displacement of soft tissue pogonion. Furthermore, there was a significant mean increase of 2.20 mm in inter-alar width and a non-significant mean increase of 1.77 mm in inter-alar curvature point width. In conclusion, automatic stereophotogrammetry landmarking analysis of soft tissue effects showed downward displacement of soft tissue pogonion following bimaxillary expansion and transverse widening of the inter-alar width and a tendency towards an increase in inter-alar curvature point width after SARME.

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Estimation of brain functional connectivity from hypercapnia BOLD MRI data: Validation in a lifespan cohort of 170 subjects

Publication date: Available online 18 November 2018

Source: NeuroImage

Author(s): Xirui Hou, Peiying Liu, Hong Gu, Micaela Chan, Yang Li, Shin-Lei Peng, Gagan Wig, Yihong Yang, Denise Park, Hanzhang Lu

Abstract

Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ± 0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ± 0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.

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Implicit visual cues tune oscillatory motor activity during decision-making

Publication date: Available online 17 November 2018

Source: NeuroImage

Author(s): Andrea Alamia, Alexandre Zénon, Rufin VanRullen, Julie Duque, Gerard Derosiere

Abstract

Motor decisions entails a buildup of choice-selective activity in the motor cortex. The rate of this buildup crucially depends on the amount of evidence favoring the selection of each action choice in the visual environment. Though numerous studies have characterized how sensory evidence drives motor activity when processed consciously, very little is known about the neural mechanisms that underlie the integration of implicit sources of information.

Here, we used electroencephalography to investigate the impact of implicit visual cues on response-locked potentials and oscillatory activity in the motor cortex during decision-making. Subjects were required to select between left and right index finger responses according to the motion direction of a cloud of dots presented in one of three possible colors. Unbeknown to the participants, the color cue could bring evidence either in favor of or against the selection of the correct response.

Implicit color cues tuned choice-selective oscillatory activity in the low beta range (16–25 Hz), boosting the buildup of contralateral activity when evidence favored the selection of the correct action, while weakening it when evidence biased against the correct response. This modulation of oscillatory activity influenced the speed at which the correct action was eventually chosen. Implicit cues also altered oscillatory activity in a non-selective way in the low frequency oscillation (1–7 Hz) and high beta ranges (25–35 Hz), impacting both contralateral and ipsilateral activity. The current findings yield a critical extension of prior observations by indicating that the integration of both explicit and implicit sources of evidence tunes oscillatory motor activity during decision-making.

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Brain reading and behavioral methods provide complementary perspectives on the representation of concepts

Publication date: Available online 17 November 2018

Source: NeuroImage

Author(s): Andrew James Bauer, Marcel Adam Just

Abstract

The advent of brain reading techniques has enabled new approaches to the study of concept representation, based on the analysis of multivoxel activation patterns evoked by the contemplation of individual concepts such as animal concepts. The present fMRI study characterized the representation of 30 animal concepts. Dimensionality reduction of the multivoxel activation patterns underlying the individual animal concepts indicated that the semantic building blocks of the brain's representations of the animals corresponded to intrinsic animal properties (e.g. fierceness, intelligence, size). These findings were compared to behavioral studies of concept representation, which have typically collected pairwise similarity ratings between two concepts (e.g. Henley, 1969). Behavioral similarity judgments, by contrast, indicated that the animals were organized into taxonomically defined groups (e.g. canine, feline, equine). The difference in the results between the brain reading and behavioral approaches might derive from differences in cognitive processing during judging similarities versus contemplating one animal at a time. Brain reading approaches may have an advantage in describing thoughts about an individual concept, owing to the ability to decode brain activation patterns elicited by the brief consideration of a single concept (e.g. word reading) without a complex cognitive or behavioral task (e.g. similarity judgments). On the other hand, some behavioral tasks may tend to evoke a concept from numerous perspectives, yielding a representation of the breadth and sophistication of the concept knowledge. These results suggest that neural and behavioral measures offer complementary perspectives that together characterize the content and structure of concept representations.

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Pharmacological stress impairs working memory performance and attenuates dorsolateral prefrontal cortex glutamate modulation

Publication date: Available online 17 November 2018

Source: NeuroImage

Author(s): Eric A. Woodcock, Mark K. Greenwald, Dalal Khatib, Vaibhav A. Diwadkar, Jeffrey A. Stanley

Abstract

Working memory processes are associated with the dorsolateral prefrontal cortex (dlPFC). Prior research using proton functional magnetic resonance spectroscopy (¹H fMRS) observed significant dlPFC glutamate modulation during letter 2-back performance, indicative of working memory-driven increase in excitatory neural activity. Acute stress has been shown to impair working memory performance. Herein, we quantified dlPFC glutamate modulation during working memory under placebo (oral lactose) and acute stress conditions (oral yohimbine 54 mg + hydrocortisone 10 mg). Using a double-blind, randomized crossover design, participants (N = 19) completed a letter 2-back task during left dlPFC ¹H fMRS acquisition (Brodmann areas 45/46; 4.5 cm³). An automated fitting procedure integrated with LCModel was used to quantify glutamate levels. Working memory-induced glutamate modulation was calculated as percentage change in glutamate levels from passive visual fixation to 2-back levels. Results indicated acute stress significantly attenuated working memory-induced glutamate modulation and impaired 2-back response accuracy, relative to placebo levels. Follow-up analyses indicated 2-back performance significantly modulated glutamate levels relative to passive visual fixation during placebo but not acute stress. Biomarkers, including blood pressure and saliva cortisol, confirmed that yohimbine + hydrocortisone dosing elicited a significant physiological stress response. These findings support a priori hypotheses and demonstrate that acute stress impairs dlPFC function and excitatory activity. This study highlights a neurobiological mechanism through which acute stress may contribute to psychiatric dysfunction and derail treatment progress. Future research is needed to isolate noradrenaline vs. cortisol effects and evaluate anti-stress medications and/or behavioral interventions.

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Nonlinear Distributional Mapping (NoDiM) for harmonization across amyloid-PET radiotracers

Publication date: Available online 17 November 2018

Source: NeuroImage

Author(s): Michael J. Properzi, Rachel F. Buckley, Jasmeer P. Chhatwal, Michael C. Donohue, Cristina Lois, Elizabeth C. Mormino, Keith A. Johnson, Reisa A. Sperling, Aaron P. Schultz

Abstract

Introduction

There is a growing need in clinical research domains for direct comparability between amyloid-beta (Aβ) Positron Emission Tomography (PET) measures obtained via different radiotracers and processing methodologies. Previous efforts to provide a common measurement scale fail to account for non-linearities between measurement scales that can arise from these differences. We introduce a new application of distribution mapping, based on well established statistical orthodoxy, that we call Nonlinear Distribution Mapping (NoDiM). NoDiM uses cumulative distribution functions to derive mappings between Aβ-PET measurements from different tracers and processing streams that align data based on their location in their respective distributions.

Methods

Utilizing large datasets of Florbetapir (FBP) from the Alzheimer's Disease Neuroimaging Initiative (n = 349 female (%) = 53) and Pittsburgh Compound B (PiB) from the Harvard Aging Brain Study (n = 305 female (%) = 59.3) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (n = 184 female (%) = 53.3), we fit explicit mathematical models of a mixture of two normal distributions, with parameter estimates from Gaussian Mixture Models, to each tracer's empirical data. We demonstrate the accuracy of these fits, and then show the ability of NoDiM to transform FBP measurements into PiB-like units.

Results

A mixture of two normal distributions fit both the FBP and PiB empirical data and provides a strong basis for derivation of a transfer function. Transforming Aβ-PET data with NoDiM results in FBP and PiB distributions that are closely aligned throughout their entire range, while a linear transformation does not. Additionally the NoDiM transform better matches true positive and false positive profiles across tracers.

Discussion

The NoDiM transformation provides a useful alternative to the linear mapping advocated in the Centiloid project, and provides improved correspondence between measurements from different tracers across the range of observed values. This improved alignment enables disparate measures to be merged on to continuous scale, and better enables the use of uniform thresholds across tracers.

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