Treatment of Patients with Vocal Fold Atrophy and Comorbid Essential Voice Tremor: Long-Term Injection Augmentation Outcomes After Successful Diagnostic Vocal Fold Injection Augmentation

Vocal fold injection augmentation (VFIA) is employed diagnostically for patients with subtle glottic insufficiency. Its use in patients with both vocal fold atrophy and benign essential voice tremor (EVT) has been reported but not after durable augmentation. This study intends to evaluate the success of durable VFIA using either autologous fat or calcium hydroxylapatite in patients with both vocal fold atrophy and comorbid EVT.

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Biobehavioral Measures of Presbylaryngeus

The objective of this observational study was to assess the relationship between established aging biobehavioral measures and voice decline in normally aging adults.

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Anti-microbial Resistance In Atopic Dermatitis: Need for an Urgent Rethink

Atopic dermatitis (AD) results from a complex interplay of host genetic and environmental factors. There is a long established association between AD and Staphylococcus aureus. In healthy individuals this organism has a dichotomous relationship with the host, being a frequent component of the human microbiome, carried asymptomatically, and on occasion, an opportunistic pathogen capable of causing or influencing a broad ranging disease. In AD, high carriage rates of S. aureus on affected skin is commonly observed, with recent meta-analysis evidence demonstrating colonisation in approximately 70% of affected individuals 1.

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Corrigendum to “National Wisdom Tooth Treatment Audit” [Br. J. Oral Maxillofac. Surg. 54 (10) (December 2016) e71]

The authors regret that Kate Matin's name was missed of the author list in the original article. It appears correctly above.

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Elevated expression of IL-17RB and ST2 on myeloid dendritic cells is associated with a Th2-skewed eosinophilic inflammation in nasal polyps

Interleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure...

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Advancements in MAPK signaling pathways and MAPK‐targeted therapies for ameloblastoma: A review

Abstract

Numerous signal transduction pathways are closely associated with the occurrence, development, and prognosis of ameloblastoma(AM). Mitogen‐activated protein kinase (MAPK) is a serine/threonine‐specific protein kinase that transduces intracellular signals in critical cellular phenomena. A number of recent analyses have reported that the MAPK signaling pathway contributes significantly to AM. High‐throughput DNA sequencing methods, such as next‐generation sequencing using Illumina have yielded advancements in studies on MAPK signaling pathways and their association with AM; in particular, BRAF V600E is mediated by the activation of the Ras/Raf/MAPK pathway. This review discusses advancements in studies on MAPK signaling pathways and MAPK‐targeted inhibitors or antibodies, along with the merits and demerits of MAPK‐targeted therapies, finally followed by a discussion regarding more efficient potential MAPK‐targeted therapies to treat AM with few side effects, thereby providing novel insights into targeted therapy for AM.

This article is protected by copyright. All rights reserved.

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Overexpression of ADAR1 into the cytoplasm correlates with a better prognosis of patients with oral squamous cells carcinoma

Abstract

Background

ADAR1 is an enzymatic protein, which catalyzes a RNA‐editing reaction by converting Adenosine to Inosine and its expression has been found to be dysregulated in many cancer types. The aim of this study was to analyze the expression of ADAR1 in oral squamous cells carcinoma.

Methods

In order to analyze the ADAR1 mRNA expression, data from The Cancer Genome Atlas (TCGA) database were downloaded and analyzed. In addition, immunohistochemistry analysis was performed on an institutional database including 46 samples of oral squamous cell carcinoma in a tissue microarray (TMA).

Results

No statistically significant correlation linked the mRNA ADAR1 expression to any clinic‐pathological variables in the TCGA database. Immunohistochemistry analysis of ADAR1 showed different expression between normal mucosa and tumor tissue. Focusing on the subcellular localization, the nuclear expression of ADAR1 correlated with higher grading of differentiation (ρ = 0,442 p‐value = 0,002); the general expression of ADAR1 either in cytoplasm or in nuclei, correlated with the Gender of patients (Cytoplasm expression: ρ = ‐0,295; p‐value = 0,049; while for nuclear expression: ρ = +0,374 p = 0,011); cytosol expression resulted to be an independent protective prognostic factor (HR = 0,047; C.I. 95% 0,007‐0,321; p‐value = 0,002).

Conclusion

Higher expression of ADAR1 into the cytoplasm resulted to be an independent prognostic factor. In order to understand ADAR1 role in cancer, further studies should be performed, in bigger cohort and under a bio‐molecular point of view.

This article is protected by copyright. All rights reserved.

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Long term effects upon rituximab treatment of acquired angio‐edema due to c1‐inhibitor deficiency

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Dupilumab reduces local type 2 pro‐inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis

Abstract

Background

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2‐mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin‐4 receptor α (IL‐4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (e.g. atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo‐controlled, phase 2 trial (NCT01920893).

Methods

Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks.

Results

With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (LS mean area under the curve from 0–16 weeks for the change from baseline) vs placebo for eotaxin‐3 (−30.06 vs −0.86 pg/mL; P=0.0008) and total IgE (−7.90 vs −1.86 IU/mL; P=0.022)). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 versus baseline for ECP (P=0.008), eotaxin‐2 (P=0.008), eotaxin‐3 (P=0.031), pulmonary and activation‐regulated chemokine (P=0.016), IgE (P=0.023), and IL‐13 (P=0.031).

Conclusions

Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL‐4Rα signaling suppresses IL‐4‐/IL‐13‐dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.

This article is protected by copyright. All rights reserved.

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Computational fluid dynamics after endoscopic endonasal skull base surgery—possible empty nose syndrome in the context of middle turbinate resection

Background

Empty nose syndrome (ENS) is a rare and debilitating disease with a controversial definition, etiology, and treatment. One puzzling fact is that patients who undergo an endoscopic endonasal approach (EEA) often have resection of multiple anatomic structures, yet seldom develop ENS. In this pilot study, we analyzed and compared the computational fluid dynamics (CFD) and symptoms among post‐EEA patients, ENS patients, and healthy subjects.

Methods

Computed tomography scans of 4 post‐EEA patients were collected and analyzed using CFD techniques. Two patients had significant ENS symptoms based on results of the Empty Nose Syndrome 6‐item Questionnaire (score >11), whereas the other 2 were asymptomatic. As a reference, their results were compared with previously published CFD results of 27 non‐EEA ENS patients and 42 healthy controls.

Results

Post‐EEA patients with ENS symptoms had a similar nasal airflow pattern as non‐EEA ENS patients. This pattern differed significantly from that of EEA patients without ENS symptoms and healthy controls. Overall, groups with ENS symptoms exhibited airflow dominant in the middle meatus region and a significantly lower percentage of airflow in the inferior turbinate region (EEA with ENS, 17.74 ± 4.00% vs EEA without ENS, 51.25 ± 3.33% [t test, p < 0.02]; non‐EEA ENS, 25.8 ± 17.6%; healthy subjects, 36.5 ± 15.9%) as well as lower peak wall shear stress (EEA with ENS, 0.30 ± 0.13 Pa vs EEA without ENS, 0.61 ± 0.03 Pa [p = 0.003]; non‐EEA ENS, 0.58 ± 0.24 Pa; healthy subjects, 1.18 ± 0.81 Pa).

Conclusion

These results suggest that turbinectomy and/or posterior septectomy may have a varying functional impact and that ENS symptoms go beyond anatomy and correlate with aerodynamic changes. The findings open the door for CFD as a potential objective diagnosis tool for ENS.

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Noninvasive exosomal proteomic biosignatures, including cystatin SN, peroxiredoxin‐5, and glycoprotein VI, accurately predict chronic rhinosinusitis with nasal polyps

Background

Exosomes are secreted epithelial‐derived vesicles that contain a conserved protein array representative of their parent cell. Exosomes may be reproducibly and noninvasively purified from nasal mucus. The exosomal proteome can be quantified using SOMAscan^TM, a highly multiplexed, aptamer‐based proteomic platform. The purpose of this study was to determine whether chronic rhinosinusitis with nasal polyps (CRSwNP) has a unique predictive exosomal proteomic biosignature.

Methods

Exosomes were isolated from whole mucus sampled from control and CRSwNP patients (n = 20 per group) by differential ultracentrifugation. The SOMAscan^TM platform was used to simultaneously quantify 1310 biologically relevant human proteins. Matched tissue and whole mucus proteomes were also analyzed. Differential protein expression and discriminatory power were calculated using the unweighted pair group method with arithmetic‐mean and principal component analysis, respectively. Bioinformatic analysis was performed using Ingenuity Pathway, MetaCore, and GeneMANIA analyses.

Results

The exosomal proteome demonstrated 123 significantly (p < 0.05) differentially regulated proteins in CRSwNP relative to control. Eighty of these proteins overlapped with the matched CRSwNP tissue proteome as compared with only 4 among matched whole mucus samples. Forty‐three significantly dysregulated pathway networks overlapped between the exosomal and tissue proteome in CRSwNP as compared with only 3 among matched whole mucus samples. The best‐performing protein set (cystatin‐SN, peroxiredoxin‐5, and glycoprotein VI) achieved an area under the curve (AUC) value of up to 99%.

Conclusion

Our data contribute a significant advance in the development of a reproducible, noninvasive, serial, and quantitative "liquid biopsy" for rhinosinusitis. The exosomal proteomic approach has revealed a unique biosignature associated with CRSwNP, which outperforms whole mucus sampling, and thus provides a method of noninvasive disease detection and proposes new potential therapeutic targets.

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Endoscopic Evaluation of the Eustachian Tube: assessment of a novel tool for grading Eustachian tube inflammation

Background

Signs of inflammation are commonly encountered during endoscopic examination of the Eustachian tube (ET) region. The clinical applicability of these findings may be enhanced by use of a standardized assessment score.

Methods

Digital video recordings were obtained of 50 nasal endoscopy examinations of the nasopharyngeal portion of the ET. Four fellowship‐trained rhinologists independently reviewed the videos with regard to specific physical findings: edema of the ET torus, erythema of the ET torus, exudate at the ET orifice, and presence of tubal tonsil. Scoring of this Endoscopic Evaluation of the Eustachian Tube (3ET) was reported using both 2‐point and 3‐point scales. Each reviewer repeated the scoring at a 10‐day interval. Interrater and intrarater agreement were calculated for each item and the total scores.

Results

Interrater and intrarater agreement were greater for the 3‐point scale than the 2‐point scale. Interrater agreement for overall instrument using the 3‐point scale was in the "acceptable" range for Krippendorff's alpha on both the first trial (0.6922) and second trial (0.7238). Intrarater agreement was generally "excellent" for individual items as well as the overall instrument.

Conclusion

The 3ET comprising these 4 physical findings has acceptable interrater and intrarater reliability, and may be applied to future clinical studies of ET function and disease.

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Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms

Background

Olfactory dysfunction is a common symptom of chronic rhinosinusitis (CRS). We previously identified several cytokines potentially linked to smell loss, potentially supporting an inflammatory etiology for CRS‐associated olfactory dysfunction. In the current study we sought to validate patterns of olfactory dysfunction in CRS using hierarchical cluster analysis, machine learning algorithms, and multivariate regression.

Methods

CRS patients undergoing functional endoscopic sinus surgery were administered the Smell Identification Test (SIT) preoperatively. Mucus was collected from the middle meatus using an absorbent polyurethane sponge and 17 inflammatory mediators were assessed using a multiplexed flow‐cytometric bead assay. Hierarchical cluster analysis was performed to characterize inflammatory patterns and their association with SIT scores. The random forest approach was used to identify cytokines predictive of olfactory function.

Results

One hundred ten patients were enrolled in the study. Hierarchical cluster analysis identified 5 distinct CRS clusters with statistically significant differences in SIT scores observed between individual clusters (p < 0.001). A majority of anosmic patients were found in a single cluster, which was additionally characterized by nasal polyposis (100%) and a high incidence of allergic fungal rhinosinusitis (50%) and aspirin‐exacerbated respiratory disease (AERD) (33%). A random forest approach identified a strong association between olfaction and the cytokines interleukin (IL)‐5 and IL‐13. Multivariate modeling identified AERD, computed tomography (CT) score, and IL‐2 as the variables most predictive of olfactory function.

Conclusion

Olfactory dysfunction is associated with specific CRS endotypes characterized by severe nasal polyposis, tissue eosinophilia, and AERD. Mucus IL‐2 levels, CT score, and AERD were independently associated with smell loss.

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Sensorimotor Speech Processing: A Brief Introduction to the Special Issue

Publication date: December 2018

Source: Brain and Language, Volume 187

Author(s): Riikka Möttönen, Patti Adank, Jeremy I. Skipper

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Editorial Board

Publication date: December 2018

Source: Brain and Language, Volume 187

Author(s):

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Assessing autism at its social and developmental roots: A review of Autism Spectrum Disorder studies using functional near-infrared spectroscopy

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Tao Liu, Xingchen Liu, Li Yi, Chaozhe Zhu, Patrick S. Markey, Matthew Pelowski

Abstract

We review a relatively new method for studying the developing brain in children and infants with Autism Spectrum Disorder (ASD). Despite advances in behavioral screening and brain imaging, due to paradigms that do not easily allow for testing of awake, very young, and socially-engaged children—i.e., the social and the baby brain—the biological underpinnings of this disorder remain a mystery. We introduce an approach based on functional near-infrared spectroscopy (fNIRS), which offers a noninvasive imaging technique for studying functional activations by measuring changes in the brain's hemodynamic properties. This further enables measurement of brain activation in upright, interactive settings, while maintaining general equivalence to fMRI findings. We review the existing studies that have used fNIRS for ASD, discussing their promise, limitations, and their technical aspects, gearing this study to the researcher who may be new to this technique and highlighting potential targets for future research.

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The infant motor system predicts actions based on visual statistical learning

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Claire D. Monroy, Marlene Meyer, Lisanne Schröer, Sarah A. Gerson, Sabine Hunnius

Abstract

Motor theories of action prediction propose that our motor system combines prior knowledge with incoming sensory input to predict other people's actions. This prior knowledge can be acquired through observational experience, with statistical learning being one candidate mechanism. But can knowledge learned through observation alone transfer into predictions generated in the motor system? To examine this question, we first trained infants at home with videos of an unfamiliar action sequence featuring statistical regularities. At test, motor activity was measured using EEG and compared during perceptually identical time windows within the sequence that preceded actions which were either predictable (deterministic) or not predictable (random). Findings revealed increased motor activity preceding the deterministic but not the random actions, providing the first evidence that the infant motor system can use knowledge from statistical learning to predict upcoming actions. As such, these results support theories in which the motor system underlies action prediction.

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The dynamics of cortical folding waves and prematurity-related deviations revealed by spatial and spectral analysis of gyrification

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Jessica Dubois, Julien Lefèvre, Hugo Angleys, François Leroy, Clara Fischer, Jessica Lebenberg, Ghislaine Dehaene-Lambertz, Cristina Borradori-Tolsa, François Lazeyras, Lucie Hertz-Pannier, Jean-François Mangin, Petra S. Hüppi, David Germanaud

Abstract

In the human brain, the appearance of cortical sulci is a complex process that takes place mostly during the second half of pregnancy, with a relatively stable temporal sequence across individuals. Since deviant gyrification patterns have been observed in many neurodevelopmental disorders, mapping cortical development in vivo from the early stages on is an essential step to uncover new markers for diagnosis or prognosis. Recently this has been made possible by MRI combined with post-processing tools, but the reported results are still fragmented. Here we aimed to characterize the typical folding progression ex utero from the pre- to the post-term period, by considering 58 healthy preterm and full-term newborns and infants imaged between 27 and 62 weeks of post-menstrual age. Using a method of spectral analysis of gyrification (SPANGY), we detailed the spatial-frequency structure of cortical patterns in a quantitative way. The modeling of developmental trajectories revealed three successive waves that might correspond to primary, secondary and tertiary folding. Some deviations were further detected in 10 premature infants without apparent neurological impairment and imaged at term equivalent age, suggesting that our approach is sensitive enough to highlight the subtle impact of preterm birth and extra-uterine life on folding.

Graphical abstract

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Assessment of cerebral blood flow in neonates and infants: A phase-contrast MRI study

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Peiying Liu, Ying Qi, Zixuan Lin, Qiyong Guo, Xiaoming Wang, Hanzhang Lu

Abstract

Abnormal cerebral blood flow (CBF) is implicated in several neonatal and infant diseases. However, measurement of CBF in this population remains difficult and has not been used in routine clinical MRI. Arterial spin labeling (ASL) methods suffer from both low SNR and poor quantification when applied to very young children. Furthermore, rapid change in brain physiology in this age range makes it difficult to choose sequence parameters such as labeling pulse flip angle and post labeling delay. Phase-contrast (PC) MRI is another approach to measure flow. It provides fast and reliable global CBF assessment, and has great promises in pediatric applications. In this study, we aimed to apply PC-MRI technique for CBF quantification in neonates and infants up to 18 months of age. We first compared several implementations of time-of-flight (TOF) MR angiogram for the visualization of brain's feeding arteries, which provides anatomical information for the positioning of PC-MRI scans. We then measured flow velocity and CBF of the internal carotid artery (ICA) and vertebral artery (VA) in 21 subjects (age 34–114 gestational weeks, 3 females, 18 males), using six encoding velocities (Venc) in each vessel. In ICA, peak arterial flow velocity was 10.2 cm/s at birth and increased to 56.0 cm/s at 18 months old. These values were 4.5–36.3 cm/s, respectively, for VA. CBF after accounting for brain volume revealed a significant (p < 0.001) age-related increase from 13.1 to 84.7 ml/100  g/min within the first 18 months after birth. Based on the peak flow velocity, we provided age-specific recommendations for Venc selection in PC-MRI when one only has time for one scan. The present study used a multi-Venc scheme to determine flow velocities in major feeding arteries of infant brain and may lay a foundation for accurate measurement of whole-brain CBF in this population.

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Computational neuroanatomy of baby brains: A review

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Gang Li, Li Wang, Pew-Thian Yap, Fan Wang, Zhengwang Wu, Yu Meng, Pei Dong, Jaeil Kim, Feng Shi, Islem Rekik, Weili Lin, Dinggang Shen

Abstract

The first postnatal years are an exceptionally dynamic and critical period of structural, functional and connectivity development of the human brain. The increasing availability of non-invasive infant brain MR images provides unprecedented opportunities for accurate and reliable charting of dynamic early brain developmental trajectories in understanding normative and aberrant growth. However, infant brain MR images typically exhibit reduced tissue contrast (especially around 6 months of age), large within-tissue intensity variations, and regionally-heterogeneous, dynamic changes, in comparison with adult brain MR images. Consequently, the existing computational tools developed typically for adult brains are not suitable for infant brain MR image processing. To address these challenges, many infant-tailored computational methods have been proposed for computational neuroanatomy of infant brains. In this review paper, we provide a comprehensive review of the state-of-the-art computational methods for infant brain MRI processing and analysis, which have advanced our understanding of early postnatal brain development. We also summarize publically available infant-dedicated resources, including MRI datasets, computational tools, grand challenges, and brain atlases. Finally, we discuss the limitations in current research and suggest potential future research directions.

Graphical abstract

T1w, T2w, FA images, tissue segmentation results as well as the reconstructed inner and outer surfaces of a typically-developing infant, scanned longitudinally at 2 weeks, 3, 6, 9 and 12 months of age. Inner surfaces are color-coded with the maximum principal curvature, and outer surfaces are color-coded with cortical thickness.

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The UNC/UMN Baby Connectome Project (BCP): An overview of the study design and protocol development

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Brittany R. Howell, Martin A. Styner, Wei Gao, Pew-Thian Yap, Li Wang, Kristine Baluyot, Essa Yacoub, Geng Chen, Taylor Potts, Andrew Salzwedel, Gang Li, John H. Gilmore, Joseph Piven, J. Keith Smith, Dinggang Shen, Kamil Ugurbil, Hongtu Zhu, Weili Lin, Jed T. Elison

Abstract

The human brain undergoes extensive and dynamic growth during the first years of life. The UNC/UMN Baby Connectome Project (BCP), one of the Lifespan Connectome Projects funded by NIH, is an ongoing study jointly conducted by investigators at the University of North Carolina at Chapel Hill and the University of Minnesota. The primary objective of the BCP is to characterize brain and behavioral development in typically developing infants across the first 5 years of life. The ultimate goals are to chart emerging patterns of structural and functional connectivity during this period, map brain-behavior associations, and establish a foundation from which to further explore trajectories of health and disease. To accomplish these goals, we are combining state of the art MRI acquisition and analysis techniques, including high-resolution structural MRI (T1-and T2-weighted images), diffusion imaging (dMRI), and resting state functional connectivity MRI (rfMRI). While the overall design of the BCP largely is built on the protocol developed by the Lifespan Human Connectome Project (HCP), given the unique age range of the BCP cohort, additional optimization of imaging parameters and consideration of an age appropriate battery of behavioral assessments were needed. Here we provide the overall study protocol, including approaches for subject recruitment, strategies for imaging typically developing children 0–5 years of age without sedation, imaging protocol and optimization, a description of the battery of behavioral assessments, and QA/QC procedures. Combining HCP inspired neuroimaging data with well-established behavioral assessments during this time period will yield an invaluable resource for the scientific community.

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Sulcal pits and patterns in developing human brains

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Kiho Im, P. Ellen Grant

Abstract

Spatial distribution and specific geometric and topological patterning of early sulcal folds have been hypothesized to be under stronger genetic control and are more associated with optimal organization of cortical functional areas and their white matter connections, compared to later developing sulci. Several previous studies of sulcal pit (putative first sulcal fold) distribution and sulcal pattern analyses using graph structures have provided evidence of the importance of sulcal pits and patterns as remarkable anatomical features closely related to human brain function, suggesting additional insights concerning the anatomical and functional development of the human brain. Recently, early sulcal folding patterns have been observed in healthy fetuses and fetuses with brain abnormalities such as polymicrogyria and agenesis of corpus callosum. Graph-based quantitative sulcal pattern analysis has shown high sensitivity in detecting emerging subtle abnormalities in cerebral cortical growth in early fetal stages that are difficult to detect via qualitative visual assessment or using traditional cortical measures such as gyrification index and curvature. It has proven effective for characterizing genetically influenced early cortical folding development. Future studies will be aimed at better understanding a comprehensive map of spatio-temporal dynamics of fetal cortical folding in a large longitudinal cohort in order to examine individual clinical fetal MRIs and predict postnatal neurodevelopmental outcomes from early fetal life.

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Baby brain atlases

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Kenichi Oishi, Linda Chang, Hao Huang

Abstract

The baby brain is constantly changing due to its active neurodevelopment, and research into the baby brain is one of the frontiers in neuroscience. To help guide neuroscientists and clinicians in their investigation of this frontier, maps of the baby brain, which contain a priori knowledge about neurodevelopment and anatomy, are essential. "Brain atlas" in this review refers to a 3D-brain image with a set of reference labels, such as a parcellation map, as the anatomical reference that guides the mapping of the brain. Recent advancements in scanners, sequences, and motion control methodologies enable the creation of various types of high-resolution baby brain atlases. What is becoming clear is that one atlas is not sufficient to characterize the existing knowledge about the anatomical variations, disease-related anatomical alterations, and the variations in time-dependent changes. In this review, the types and roles of the human baby brain MRI atlases that are currently available are described and discussed, and future directions in the field of developmental neuroscience and its clinical applications are proposed. The potential use of disease-based atlases to characterize clinically relevant information, such as clinical labels, in addition to conventional anatomical labels, is also discussed.

Graphical abstract

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Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Lara Lordier, Serafeim Loukas, Frédéric Grouiller, Andreas Vollenweider, Lana Vasung, Djalel-Eddine Meskaldij, Fleur Lejeune, Marie Pascale Pittet, Cristina Borradori-Tolsa, François Lazeyras, Didier Grandjean, Dimitri Van De Ville, Petra S. Hüppi

Abstract

Neonatal Intensive Care Units (NICU) provide special equipment designed to give life support for the increasing number of prematurely born infants and assure their survival. More recently NICU's strive to include developmentally oriented care and modulate sensory input for preterm infants. Music, among other sensory stimuli, has been introduced into NICUs, but without knowledge on the basic music processing in the brain of preterm infants. In this study, we explored the cortico-subcortical music processing of different types of conditions (Original music, Tempo modification, Key transposition) in newborns shortly after birth to assess the effective connectivity of the primary auditory cortex with the entire newborn brain. Additionally, we investigated if early exposure during NICU stay modulates brain processing of music in preterm infants at term equivalent age. We approached these two questions using Psychophysiological Interaction (PPI) analyses. A group of preterm infants listened to music (Original music) starting from 33 weeks postconceptional age until term equivalent age and were compared to two additional groups without music intervention; preterm infants and full-term newborns. Auditory cortex functional connectivity with cerebral regions known to be implicated in tempo and familiarity processing were identified only for preterm infants with music training in the NICU. Increased connectivity between auditory cortices and thalamus and dorsal striatum may not only reflect their sensitivity to the known music and the processing of its tempo as familiar, but these results are also compatible with the hypothesis that the previously listened music induces a more arousing and pleasant state. Our results suggest that music exposure in NICU's environment can induce brain functional connectivity changes that are associated with music processing.

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Ultrafast Doppler for neonatal brain imaging

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Charlie Demené, Jérôme Mairesse, Jérôme Baranger, Mickael Tanter, Olivier Baud

Abstract

The emergence of functional neuroimaging has dramatically accelerated our understanding of the human mind. The advent of functional Magnetic Resonance Imaging paved the way for the next decades' major discoveries in neuroscience and today remains the "gold standard" for deep brain imaging. Recent improvements in imaging technology have been somewhat limited to incremental innovations of mature techniques instead of breakthroughs. Recently, the use of ultrasonic plane waves transmitted at ultrafast frame rates was shown to highly increase Doppler ultrasound sensitivity to blood flows in small vessels in rodents. By identifying regions of brain activation through neurovascular coupling, Ultrafast Doppler was entering into the world of preclinical neuroimaging. The combination of many advantages, including high spatio-temporal resolution, deep penetration, high sensitivity and portability provided unique information about brain function. Recently, Ultrafast Doppler imaging was found able to non-invasively image the spatial and temporal dynamics of microvascular changes during seizures and interictal periods with an unprecedented resolution at bedside. This review summarizes the technical basis, the added value and the clinical perspectives provided by this new brain imaging modality that could create a breakthrough in the knowledge of brain hemodynamics, brain insult, and neuroprotection.

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Delineation of early brain development from fetuses to infants with diffusion MRI and beyond

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Minhui Ouyang, Jessica Dubois, Qinlin Yu, Pratik Mukherjee, Hao Huang

Abstract

Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders.

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Maternal Interleukin-6 concentration during pregnancy is associated with variation in frontolimbic white matter and cognitive development in early life

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Jerod M. Rasmussen, Alice M. Graham, Sonja Entringer, John H. Gilmore, Martin Styner, Damien A. Fair, Pathik D. Wadhwa, Claudia Buss

Abstract

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life.

Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ± 2.8 weeks [S.D.]), mid (20.4 ± 1.5 weeks [S.D.]) and late (30.3 ± 1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ± 1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ± 3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment.

Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central portion of the UF proximal to the amygdala. Furthermore, maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p < 0.05), resulting in a null association between maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated with offspring cognition at 12-mo age, and this association was mediated by FA growth across the first year of postnatal life.

Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context.

Graphical abstract

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Early life predictors of brain development at term-equivalent age in infants born across the gestational age spectrum

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Deanne K. Thompson, Claire E. Kelly, Jian Chen, Richard Beare, Bonnie Alexander, Marc L. Seal, Katherine Lee, Lillian G. Matthews, Peter J. Anderson, Lex W. Doyle, Alicia J. Spittle, Jeanie L.Y. Cheong

Abstract

Background

It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32–33 weeks' GA) and late (LP; 34–36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38–44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT).

Methods

Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing.

Results

Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values.

Conclusion

Early life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum.

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A review on neuroimaging studies of genetic and environmental influences on early brain development

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Wei Gao, Karen Grewen, Rebecca C. Knickmeyer, Anqi Qiu, Andrew Salzwedel, Weili Lin, John H. Gilmore

Abstract

The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions.

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Challenges in pediatric neuroimaging

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Matthew J. Barkovich, Yi Li, Rahul S. Desikan, A. James Barkovich, Duan Xu

Abstract

Pediatric neuroimaging is challenging due the rapid structural, metabolic, and functional changes that occur in the developing brain. A specially trained team is needed to produce high quality diagnostic images in children, due to their small physical size and immaturity. Patient motion, cooperation and medical condition dictate the methods and equipment used. A customized approach tailored to each child's age and functional status with the appropriate combination of dedicated staff, imaging hardware, and software is key; these range from low-tech techniques, such as feed and swaddle, to specialized small bore MRI scanners, MRI compatible incubators and neonatal head coils. New pre-and post-processing techniques can also compensate for the motion artifacts and low signal that often degrade neonatal scans.

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Multi-task prediction of infant cognitive scores from longitudinal incomplete neuroimaging data

Publication date: 15 January 2019

Source: NeuroImage, Volume 185

Author(s): Ehsan Adeli, Yu Meng, Gang Li, Weili Lin, Dinggang Shen

Abstract

Early postnatal brain undergoes a stunning period of development. Over the past few years, research on dynamic infant brain development has received increased attention, exhibiting how important the early stages of a child's life are in terms of brain development. To precisely chart the early brain developmental trajectories, longitudinal studies with data acquired over a long-enough period of infants' early life is essential. However, in practice, missing data from different time point(s) during the data gathering procedure is often inevitable. This leads to incomplete set of longitudinal data, which poses a major challenge for such studies. In this paper, prediction of multiple future cognitive scores with incomplete longitudinal imaging data is modeled into a multi-task machine learning framework. To efficiently learn this model, we account for selection of informative features (i.e., neuroimaging morphometric measurements for different time points), while preserving the structural information and the interrelation between these multiple cognitive scores. Several experiments are conducted on a carefully acquired in-house dataset, and the results affirm that we can predict the cognitive scores measured at the age of four years old, using the imaging data of earlier time points, as early as 24 months of age, with a reasonable performance (i.e., root mean square error of 0.18).

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Acoustic Predictors of Gender Attribution, Masculinity–Femininity, and Vocal Naturalness Ratings Amongst Transgender and Cisgender Speakers

Publication date: Available online 28 November 2018

Source: Journal of Voice

Author(s): Teresa L.D. Hardy, Jana M. Rieger, Kristopher Wells, Carol A. Boliek

Abstract

Purpose

This study aimed to identify the most salient set of acoustic predictors of (1) gender attribution; (2) perceived masculinity–femininity; and (3) perceived vocal naturalness amongst a group of transgender and cisgender speakers to inform voice and communication feminization training programs. This study used a unique set of acoustic variables and included a third, androgynous, choice for gender attribution ratings.

Method

Data were collected across two phases and involved two separate groups of participants: communicators and raters. In the first phase, audio recordings were captured of communicators (n = 40) during cartoon retell, sustained vowel, and carrier phrase tasks. Acoustic measures were obtained from these recordings. In the second phase, raters (n = 20) provided ratings of gender attribution, perceived masculinity–femininity, and vocal naturalness based on a sample of the cartoon description recording.

Results

Results of a multinomial logistic regression analysis identified mean fundamental frequency (f_o) as the sole acoustic measure that changed the odds of being attributed as a woman or ambiguous in gender rather than as a man. Multiple linear regression analyses identified mean f_o, average formant frequency of /i/, and mean sound pressure level as predictors of masculinity–femininity ratings and mean f_o, average formant frequency, and rate of speech as predictors of vocal naturalness ratings.

Conclusion

The results of this study support the continued targeting of f_o and vocal tract resonance in voice and communication feminization/masculinization training programs and provide preliminary evidence for more emphasis being placed on vocal intensity and rate of speech. Modification of these voice parameters may help clients to achieve a natural-sounding voice that satisfactorily represents their affirmed gender.

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Multivariate Analysis of Radiologists’ Usage of Phrases that Convey Diagnostic Certainty

Publication date: Available online 28 November 2018

Source: Academic Radiology

Author(s): Ronilda Lacson, Eseosa Odigie, Aijia Wang, Neena Kapoor, Atul Shinagare, Giles Boland, Ramin Khorasani

Rationale and Objectives

To quantify the use of Diagnostic Certainty Phrases (DCP) in radiology reports, including DCPs with good agreement (including "diagnostic of," "unlikely" and "represents") in connoting degree of certainty between providers based on previous studies; and to assess whether modality, presence of a trainee, radiologic subspecialty, and individual radiologists are associated with the usage of DCPs with good agreement.

Materials and Methods

This retrospective, IRB-approved study was conducted at an academic medical center. Radiology reports that contain DCPs were identified using information retrieval from all reports generated in 2016, excluding mammograms, obstetrical ultrasound, bone densitometry, and interventional studies. DCPs connoting good agreement were further noted. Of the reports that contained DCPs, a two-level hierarchical generalized linear model with attending as the level-two variable was performed comparing the use of DCP with good agreement while considering trainee involvement, modality, and subspecialty.

Results

A total of 159,151 reports out of 370,881 were found to have at least one DCP (43%). Reports of CT scans had the most number of DCP (68% of all CT reports). Breast and abdomen subspecialties were associated with use of DCP with good agreement. There was significant variation in use of DCP with good agreement between physicians that could not be explained by modality, trainee presence, and subspecialty.

Conclusion

Phrases to convey diagnostic certainty were commonly used in radiology reports. There is wide variation in usage of DCP with good agreement. Future interventions to reduce variation in use of DCPs may reduce ambiguity and improve quality of radiology reports.

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Editorial Board

Publication date: December 2018

Source: Dental Materials, Volume 34, Issue 12

Author(s):

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Effect of exposure time and pre-heating on the conversion degree of conventional, bulk-fill, fiber reinforced and polyacid-modified resin composites

Publication date: Available online 28 November 2018

Source: Dental Materials

Author(s): Edina Lempel, Zsuzsanna Őri, József Szalma, Bálint Viktor Lovász, Adél Kiss, Ákos Tóth, Sándor Kunsági-Máté

Abstract

Objective

To determine the degree of conversion (DC) of different type of resin-based composites (RBC) in eight-millimeter-deep clinically relevant molds, and investigate the influence of exposure time and pre-heating on DC.

Methods

Two-millimeter-thick samples of conventional sculptable [FiltekZ250 (FZ)], flowable [Filtek Ultimate Flow (FUF)] and polyacid-modified [Twinky Star Flow (TS)] RBCs, and four-millimeter-thick samples of flowable bulk-fill [Filtek Bulk Fill Flow (FBF), Surefil SDR (SDR)] and sculptable fibre-reinforced [EverX Posterior (EX)] RBCs were prepared in an eight-millimeter-deep mold. The RBCs temperature was pre-set to 25, 35 and 55 °C. The RBCs were photopolymerized with the recommended and its double exposure time. The DC at the top and bottom was measured with micro-Raman spectroscopy. Data were analyzed with ANOVA and Scheffe post-hoc test (p < 0.05).

Results

The differences in DC% between the top/bottom and the recommended/extended exposure time were significant for the materials, except SDR (64.5/63.0% and 67.4/63.0%). FUF (69.0% and 53.4%) and TS (64.9% and 60.9%) in 2 mm provided higher DC% at the top and bottom with the recommended curing time, compared to the other materials, except SDR. Pre-heating had negative effect on DC at the bottom in flowable RBCs (FUF: 48.9%, FBF: 36.7%, SDR: 43%, TS: 54.7%). Pre-heating to 55 °C significantly increased the DC% in fibre-reinforced RBC (75.0% at the top, 64.7% at the bottom).

Significance

Increased exposure time improves the DC for each material. Among bulk-fills, only SDR performed similarly, compared to the two-millimeter-thick flowable RBCs. Pre-heating of low-viscosity RBCs decreased the DC% at the bottom. Pre-heating of fibre-reinforced RBC to 55 °C increased the DC% at a higher rate than the extended curing time.

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Effects of anterior tongue strengthening exercises on posterior tongue strength in healthy young adults

Publication date: Available online 28 November 2018

Source: Archives of Oral Biology

Author(s): Jitsuro Yano, Sayako Yamamoto-Shimizu, Tomonori Yokoyama, Isami Kumakura, Kozo Hanayama, Akio Tsubahara

Abstract

Objective

The aim of the present study was to investigate whether anterior tongue muscle strengthening exercises can affect the strength of posterior tongue muscles.

Design

Eleven healthy subjects (20.6 ± 1.2 years) were included. The subjects exercised by pushing the anterior tongue to the palate 30 times, three times a day, 3 days a weekfor 8 weeks. The exercise intensity was set at 60% of maximum tongue pressure (MTP) in the first week and 80% of MTP for the remainder of training. After the completion of training, MTP measurements were continued every month for another 3 months to evaluate whether training effects were sustained.

Results

MTP was significantly increased after 8 weeks of training compared with before training. No significant differences were seen between MTP immediately after completion of training and MTP 1-3 months after completion of training. However, MTP was significantly higher 1-3 months after completion of training than before training.

Conclusions

The present study showed significant increases in both anterior and posterior MTPs by anterior tongue muscle strengthening exercises. In the future, a database on tongue muscle strengthening exercises in elderly persons,patients with dysphagia, etc. will need to be generated, with the aim of preventing frailty.

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Horizontal alveolar transport distraction osteogenesis followed by implant placement

Publication date: Available online 28 November 2018

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): S. Uckan, G. Senol, E. Ogut, G. Muftuoglu

Abstract

Alveolar transport distraction osteogenesis (ATDO) is an alternative treatment method to vertical alveolar distraction osteogenesis in cases of large bony defects, especially when the bone is limited in size. ATDO was performed in 10 patients with 12 defects. The mean age of the patients was 39.1 years. The average bone length gain was 18.2 mm. Implants were inserted following a 3-month consolidation period. Three patients needed additional bone grafting for horizontal widening. Final prosthetic rehabilitation was performed at least 3 months following implant insertion. The mean follow-up period was 63 months and the survival rate of the 25 implants placed was 92%. All failures (n = 2) occurred during the early healing period. Although the results are not totally predictable, it can be concluded that ATDO can be effective in the reconstruction of the alveolar crest prior to implant placement.

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Influence of the anatomical form of the posterior maxilla on the reliability of superior maxillary repositioning by Le Fort I osteotomy

Publication date: Available online 28 November 2018

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): N. Tomomatsu, K. Kurohara, K. Nakakuki, H. Yoshitake, T. Kanemaru, S. Yamaguchi, T. Yoda

Abstract

Certain patients with facial deformities require superior repositioning of the maxilla via Le Fort I osteotomy; however, the magnitude of superior repositioning of the maxilla is often less than expected. In this study, the correlation between the accuracy of superior repositioning of the maxilla and the anatomical form of the maxillary posterior region was examined. Seventy-five patients who underwent Le Fort I osteotomy without forward movement of the maxilla but with superior repositioning of the maxilla were included in this study. The bone volume around the descending palatine artery (DPA), the angle of the junction between the pterygoid process and the tuberosity, and the distance between the upper second molar and the pterygoid process were measured via three-dimensional analysis. A significant negative correlation (r = −0.566) was found between the bone volume around the DPA and the ratio of repositioning (actual movement divided by expected movement). It is possible that the superior repositioning of the maxilla expected prior to surgery was not sufficiently attained because of the large volume of bone around the DPA. The results of this study show that in some patients, superior repositioning was not achieved at the expected level because of bone interference attributable to the anatomical form of the maxillary posterior region.

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Challenges in allergy immunology practice

As our knowledge base continues to increase, many of the diseases we see and treat seem to have become more complex. This may come from a variety of factors, including better technology, better research, and better diagnostic techniques, among other factors. Not that long ago, asthma was classified more simply as either "intrinsic" or "extrinsic," and rhinitis was either "allergic" or "nonallergic." Now, with the vast improvements we enjoy in the practice of medicine, we have phenotypes and endotypes; we have biomarkers, treatment guidelines, practice parame-->ters, and more.

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A new acronym for PPI-REE?

Eosinophilic esophagitis (EoE) is a complex allergic disease commonly associated with food-induced symptomatic esophageal dysfunction.1 This includes reflux, dysphagia, and dysmotility.2 Consensus guidelines have provided clinical information to guide EoE evaluation, including the use of proton pump inhibitors (PPIs), to distinguish gastroesophageal reflux disease from EoE, and observations that a unique subset of eosinophilic esophageal infiltration might be largely resolved using a PPI, also termed PPI-REE (PPI-responsive esophageal eosinophilia).

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Information for Readers

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Erratum

In the Original Article, "Omalizumab chronic spontaneous urticaria: Efficacy, safety, predictors of treatment outcome, and time to response" (Ann Allergy Asthma Immunol. 2018;121:474-478), the title should have been set as "Omalizumab in chronic spontaneous urticaria: Efficacy, safety, predictors of treatment outcome, and time to response."

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Table of Contents

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Author Index

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Information for Authors

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Editorial Board

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