Split-mouth evaluation of connective tissue graft with or without enamel matrix derivative for the treatment of isolated gingival recession defects in dogs

Abstract

Objectives

The potential additive effect of an enamel matrix derivative (EMD) to a subepithelial connective tissue graft (CTG) for recession coverage is still controversially discussed. Therefore, the aim of this study was to histologically evaluate the healing of gingival recessions treated with coronally advanced flap (CAF) and CTG with or without EMD in dogs.

Materials and methods

Gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 7 dogs. After 8 weeks of plaque accumulation and subsequent 2 weeks of chemical plaque control, the 14 chronic defects were randomized to receive either CAF with CTG (CAF/CTG) or CAF with CTG and EMD (CAF/CTG/EMD). The animals were sacrificed 10 weeks after reconstructive surgery for histologic evaluation.

Results

Treatment with CAF/CTG/EMD demonstrated statistically significantly better results in terms of probing pocket depth reduction (P < 0.05) and clinical attachment level gain (P < 0.001). The length of the epithelium was statistically significantly shorter in the CAF/CTG/EMD group than in the CAF/CTG group (1.00 ± 0.75 mm vs. 2.38 ± 1.48 mm, respectively, P < 0.01). Cementum formation was statistically significantly greater in the CAF/CTG/EMD group than following treatment with the CAF/CTG group (3.20 ± 0.89 mm vs. 1.88 ± 1.58 mm, respectively, P < 0.01). The CAF/CTG/EMD group showed statistically significantly greater complete periodontal regeneration (i.e., new cementum, new periodontal ligament, and new bone) than treatment with CAF/CTG (0.54 ± 0.73 mm vs. 0.07 ± 0.27 mm, respectively, P < 0.05).

Conclusion

Within their limits, the present findings indicate that the additional use of EMD in conjunction with CAF + CTG favors periodontal regeneration in gingival recession defects.

Clinical relevance

The present findings support the use of EMD combined with CTG and CAF for promoting periodontal regeneration in isolated gingival recession defects.

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4-D flow magnetic-resonance-imaging-derived energetic biomarkers are abnormal in children with repaired tetralogy of Fallot and associated with disease severity

Abstract

Background

Cardiac MRI plays a central role in monitoring children with repaired tetralogy of Fallot (TOF) for long-term complications. Current risk assessment is based on volumetric and functional parameters that measure late expression of underlying physiological changes. Emerging 4-D flow MRI techniques promise new insights.

Objective

To assess whether 4-D flow MRI-derived measures of blood kinetic energy (1) differentiate children and young adults with TOF from controls and (2) are associated with disease severity.

Materials and methods

Pediatric patients post TOF repair (n=21) and controls (n=24) underwent 4-D flow MRI for assessment of time-resolved 3-D blood flow. Data analysis included 3-D segmentation of the right ventricle (RV) and pulmonary artery (PA), with calculation of peak systolic and diastolic kinetic energy (KE) maps. Total KE_RV and KE_PA were determined from the sum of the KE of all voxels within the respective time-resolved segmentations.

Results

KE_PA was increased in children post TOF vs. controls across the cardiac cycle, with median 12.5 (interquartile range [IQR] 10.3) mJ/m² vs. 8.2 (4.3) mJ/m², P<0.01 in systole; and 2.3 (2.7) mJ/m² vs. 1.4 (0.9) mJ/m², P<0.01 in diastole. Diastolic KE_PA correlated with systolic KE_PA (R² 0.41, P<0.01) and with pulmonary regurgitation fraction (R² 0.65, P<0.01). Diastolic KE_RV showed similar relationships, denoting increasing KE with higher cardiac outputs and increased right heart volume loading. Diastolic KE_RV and KE_PA increased with RV end-diastolic volume in a non-linear relationship (R² 0.33, P<0.01 and R² 0.50, P<0.01 respectively), with an inflection point near 120 mL/m².

Conclusion

Four-dimensional flow-derived KE is abnormal in pediatric patients post TOF repair compared to controls and has a direct, non-linear relationship with traditional measures of disease progression. Future longitudinal studies are needed to evaluate utility for early outcome prediction in TOF.

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The South Asian Facial Anthropometric Profile: A Systematic Review

Craniofacial anatomy, as measured by facial anthropometric data, varies significantly between races. South Asia, comprised of eight countries, represents a large proportion of the global population and is the fastest-growing region of the world. This systematic review presents the facial anthropometric data collected for populations from this region.

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Semiautomatic device for in vitro/ experimental bone perforation in dental implant research

The present study presents a semiautomatic device developed to perform in vitro experiments using surgical drills for assisting dental implant research. It was built to perform tests independent of human direct contact, and contains an adjustable toolholder for engaging different types of implant contra angle hand pieces, in which different drills can be adapted. The researcher is able to make a range of adjustments on the machine, such as controlling the drilling force and depth.

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Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. The pipeline of novel targeted treatments for AD is expanding, largely based on our growing knowledge of disease mechanisms, with new therapeutics particularly focused on immune modulation.1 Most of our understanding of AD is derived from profiling tissues and blood of longstanding AD in adults, due to the difficulty of obtaining samples from infants and young children. However, initiation of AD typically happens very early in life, and the disease is already chronically established in the majority of patients by 5yrs of age.

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Neutrophil to lymphocyte ratio is a novel independent predictor of severe exacerbation in asthma patients

Severe exacerbations are well-known complications of asthma, which increase the total and asthma-related health care costs1 and decrease the quality of life of patients2. Although some exacerbation predictors have been reported3,4, it is difficult to predict and prevent severe exacerbations in a large percentage of patients affected by asthma.

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SERPING1 mutation in a rare hereditary angioedema with skin blisters

Hereditary Angioedema (HAE) is a rare, autosomal dominant disease characterized clinically by recurrent episodes of edema that may affect the skin and internal organs. The pathophysiological background of HAE is primarily an increased vascular permeability reaction to a local overproduction of bradykinin1. The most frequent dermatological manifestation is angioedema, which may occur on any part of the body and erythema marginatum is sometimes seen as symptomatic of the onset of an attack. The formation of blisters, described by some authors2-5, is an infrequent cutaneous manifestation of HAE.

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IFAR 2018 Reviewers

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Changes in the clinical and histological characteristics of Chinese chronic rhinosinusitis with nasal polyps over 11 years

Background

Traditionally, it was believed that chronic rhinosinusitis with nasal polyps (CRSwNP) demonstrated less eosinophilic and more neutrophilic inflammation in China compared to North America and Europe. However, inflammatory patterns may change over time. The study aimed to analyze the changing trends in the clinical and histological characteristics of CRSwNP over time in China.

Methods

A total of 115 consecutive CRSwNP patients from 2003 to 2005 and 114 consecutive CRSwNP patients from 2014 to 2016 were enrolled in this retrospective study. The clinical and histological data were compared between patients from the 2 time periods.

Results

The percentage of eosinophils in nasal polyp tissue increased, and the percentage of neutrophils and total inflammatory cell count decreased, over 11 years. The proportion of eosinophilic CRSwNP significantly increased from 59.1% to 73.7% over 11 years. The proportion of neutrophils and the total inflammatory cell count in nasal polyps decreased, and the proportion of eosinophilic CRSwNP patients using intranasal corticosteroids 1 month before surgery increased remarkably over 11 years. Moreover, eosinophilic CRSwNP patients had better compliance with intranasal corticosteroid use than non‐eosinophilic CRSwNP patients, and patients with comorbid allergic rhinitis and asthma had better compliance with intranasal corticosteroid use than patients without those conditions.

Conclusion

Eosinophilic CRSwNP, which was previously a minor subtype in East Asians, has increased remarkably in incidence to become the predominant CRSwNP subtype in Beijing, China, indicating that rhinologists should place greater emphasis on its diagnosis and treatment.

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Contact of the incisive canal and upper central incisors causing root resorption after retraction with orthodontic mini-implants: A CBCT study.

Related Articles

Contact of the incisive canal and upper central incisors causing root resorption after retraction with orthodontic mini-implants: A CBCT study.

Angle Orthod. 2018 Nov 28;:

Authors: Pan Y, Chen S

Abstract
OBJECTIVES:: To explore risk factors for contact between the incisive canal (IC) and upper central incisors (U1) and to evaluate the relationship between contact and root resorption using cone-beam computer tomography (CBCT).
MATERIALS AND METHODS:: This retrospective study used CBCT data of 33 patients treated by a senior orthodontist. Anterior teeth were retracted with mini-implants, and CBCT scans were taken before and after retraction. IC height and width, U1 lingual movement, and U1-IC distance and root length decrease were compared between contact and noncontact groups.
RESULTS:: Sixteen U1 roots in 11 patients touched the IC. The contact group had lower positioned ICs (2.86 ± 1.10 mm) than the noncontact group (4.07 ± 1.72 mm). The middle of the U1 roots showed more lingual movement to ICs in the contact group (2.30 ± 1.20 mm) than in the noncontact group (1.07 ± 1.16 mm). Right central incisors were closer to the IC than were the left. Root length decreased significantly more in the contact group (2.63 ± 0.93 mm) than in the noncontact group (1.14 ± 0.83 mm).
CONCLUSIONS:: There is a risk for the U1 root to contact the IC during anterior retraction when the IC is lower positioned. This contact might cause external apical root resorption.

PMID: 30484326 [PubMed - as supplied by publisher]

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Long-term stability of maxillary protraction therapy in Class III patients with complete unilateral cleft lip and palate.

Related Articles

Long-term stability of maxillary protraction therapy in Class III patients with complete unilateral cleft lip and palate.

Angle Orthod. 2018 Nov 28;:

Authors: Zhang Y, Fu Z, Jia H, Huang Y, Li X, Liu H, Li W

Abstract
OBJECTIVES:: This study evaluated the long-term stability of maxillary protraction (MP) in patients with complete unilateral cleft lip and palate (UCLP) and identified factors influencing relapse and long-term outcomes.
MATERIALS AND METHODS:: Twenty-three adolescents with UCLP who underwent MP therapy were recalled when craniofacial growth was close to completion. Subjects exhibiting reverse/positive overjets were assigned to unstable/stable groups. Lateral cephalometric measurements were made before treatment (T0), after active treatment (T1), and at the end of the growth spurt (T2).
RESULTS:: About 63% of the subjects exhibited positive overjets during follow-up. The unstable group demonstrated higher B-x and Co-Gn distances than the stable group (both P < .05) at T0. More short-term (T0-T1) sagittal advancement of point A (A-y) was evident in the unstable group than in the stable group ( P < .05), but no long-term difference was apparent between the two groups ( P = .481). During the posttreatment period (T1-T2), the SNA angle and maxillary incisor protrusion (U1-SN angle) were considerably lower in the unstable group than in the stable group (both P < .05). Overall, the unstable group exhibited a lower increase in the vertical extent of point A (A-x) than the stable group from T0 to T2 ( P < .05).
CONCLUSIONS:: In the long term, MP affords favorable maxillary advancement in patients with UCLP. A mandibular excess at T0 and vertical maxillary hypoplasia may contribute to the long-term relapse of a reverse overjet.

PMID: 30484325 [PubMed - as supplied by publisher]

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Atomic layout of an orthodontic titanium mini-implant in human tissue: Insights into the possible mechanisms during osseointegration.

Related Articles

Atomic layout of an orthodontic titanium mini-implant in human tissue: Insights into the possible mechanisms during osseointegration.

Angle Orthod. 2018 Nov 28;:

Authors: Kim JS, Ahn JP, Kim YH, Seo KW, Zadeh H, Kim SH

Abstract
OBJECTIVES:: To evaluate nanoscale molecular interactions in the interface between human bone and orthodontic titanium implants.
MATERIALS AND METHODS:: An orthodontic implant (sandblasted with large grit and with an acid-etched surface treated with Ti6A14V alloy) retrieved from the mandible of human after 2 months of healing was used to analyze the molecular interactive mechanism between the implant and the surrounding bone tissue. To preserve the natural state of the sample as much as possible, cryofixation and scanning electron microscope/focused ion beam milling without any chemical treatment were used during sample preparation. Atom probe tomography was used to investigate the chemical composition and structure at the interface between the implant and human bone tissue.
RESULTS:: Three-dimensional (3D) reconstruction of the whole sample revealed a 20 × 50-nm2 plate-like bony element diffusion layer in the sample. The iso concentration analysis of the diffusion layer indicated that the bony element, calcium, and the implant element, titanium oxide, were interspersed with each other. Detailed ionic distribution was illustrated by 3D reconstruction with partial region of interest and one-dimensional concentration profiles of the implant-bone interface.
CONCLUSIONS:: The study results advance nanoscale understanding of osseointegration and suggest a potential nanostructure for increasing bond strength of biomaterials to bone.

PMID: 30484324 [PubMed - as supplied by publisher]

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Calendar

Publication date: January 2019

Source: Ultrasound in Medicine & Biology, Volume 45, Issue 1

Author(s):

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Contents

Publication date: January 2019

Source: Ultrasound in Medicine & Biology, Volume 45, Issue 1

Author(s):

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Editorial Advisory Board

Publication date: January 2019

Source: Ultrasound in Medicine & Biology, Volume 45, Issue 1

Author(s):

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Masthead

Publication date: January 2019

Source: Ultrasound in Medicine & Biology, Volume 45, Issue 1

Author(s):

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Exceptional contact elasticity of human enamel in nanoindentation test

Publication date: Available online 30 November 2018

Source: Dental Materials

Author(s): Naofumi Shimomura, Reina Tanaka, Yo Shibata, Zhongpu Zhang, Qing Li, Jun Zhou, Wurihan, Takuma Tobe, Sachiko Ikeda, Kazuko Yoshikawa, Yukie Shimada, Takashi Miyazaki

Abstract

Objective

Tooth enamel has unsurpassed hardness and stiffness among mammalian tissue structures. Such stiff materials are usually brittle, yet mature enamel can survive for a lifetime. Understanding the nanoscale origin of enamel durability is important for developing advanced load-bearing biomaterials. Here, nanoscale exceptional contact elasticity of the human tooth enamel, based on nanoindentation tests, is reported.

Methods

Spherical indenter tips with radii of 243 and 1041 nm were used to determine stress–strain curves of enamel. Force–displacement curves were recorded using quasi-static loading strain rates of 0.031, 0.041, and 0.061 s⁻¹. The storage moduli from a superimposed signal amplitude (dynamic strain at 220 Hz) embedded during primary quasi-static loading and from quasi-static elastic theory were simultaneously measured. Modulus mapping was considered to be an extremely low quasi-static loading strain rate indentation test.

Results

The elastic limits were 7–9 GPa and 5–6 GPa for the small and large indenters, respectively. The elastic–plastic transition point and elastic modulus value increased with substantially increased quasi-static loading strain rate. The results suggested that the increase of the elastic limit during high-loading strain was associated with exceptional contact elasticity at the nanoscale of the enamel structure and the consequent extension of the contact area (i.e., a temporary pile-up response, dependent on the enamel nanocrystals and protein glue).

Significance

Structural modification at this scale effectively prevents the initiation of cracking from localized strain, thus reinforcing the bulk structure. These results may provide valuable insight for conceptualizing bio-inspired nanocomposites.

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Residual strain mapping through pair distribution function analysis of the porcelain veneer within a yttria partially stabilised zirconia dental prosthesis

Publication date: Available online 30 November 2018

Source: Dental Materials

Author(s): Alexander J.G. Lunt, Philip Chater, Annette Kleppe, Nikolaos Baimpas, Tee K. Neo, Alexander M. Korsunsky

Abstract

Objective

Residually strained porcelain is influential in the early onset of failure in Yttria Partially Stabilised Zirconia (YPSZ) – porcelain dental prosthesis. In order to improve current understanding it is necessary to increase the spatial resolution of residual strain analysis in these veneers.

Methods

Few techniques exist which can resolve residual stress in amorphous materials at the microscale resolution required. For this reason, recent developments in Pair Distribution Function (PDF) analysis of X-ray diffraction data of dental porcelain have been exploited. This approach has facilitated high-resolution (70 μm) quantification of residual strain in a YPSZ-porcelain dental prosthesis.

In order to cross-validate this technique, the sequential ring-core focused ion beam and digital image correlation approach was implemented at a step size of 50 μm. This semi-destructive technique exploits microscale strain relief to provide quantitative estimates of the near-surface residual strain.

Results

The two techniques were found to show highly comparable results. The residual strain within the veneer was found to be primarily tensile, with the highest magnitude stresses located at the YPSZ-porcelain interface where failure is known to originate. Oscillatory tensile and compressive stresses were also found in a direction parallel to the interface, likely to be induced by the multiple layering used during fabrication.

Significance

This study provides the insights required to improve prosthesis modelling, to develop new processing routes that minimise residual stress and ultimately to reduce prosthesis failure rates. The PDF approach also offers a powerful new technique for microscale strain quantification in amorphous materials.

Graphical abstract

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Influence of placement instruments on handling of dental composite materials

Publication date: Available online 30 November 2018

Source: Dental Materials

Author(s): Martin Rosentritt, Jana Hartung, Verena Preis, Stephanie Krifka

Abstract

Objective

Applicability and stickiness of dental composites are influential factors for the properties of those materials and so indirectly affect function, longevity and esthetics of composite restorations in the clinic. Thus, this in vitro study aimed for the influence of different placement instruments' diameter, geometries and coatings on the handling of uncured resin composite materials.

Methods

A survey about application technique of resin composites, placement instrument diameter, geometry and coating, and application temperature was answered by 55 German dentists in private practice. Due to these data diverse composite placement instruments were used to perform tensile tests on PMMA plates with application forces of 1 N and 2 N (v = 35 mm/min) at 25 and 37 °C. Following the dosing of a certain amount of the composite (nanohybrid, microhybrid) to the tip of the composite placement instrument, unplugging forces were determined after application and unplugging was performed.

Results

Unplugging forces were statistically significant different and varied between 0.27 N and 1.14 N. Stickiness of dental composites was dependent on the composite material itself as well as diameter, geometry and coating of the placement instruments.

Significance

Pre-clinical testing of composite materials' stickiness by unplugging forces facilitates the assessment of its handling properties.

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Antibacterial effects of polymeric PolymP-n Active nanoparticles. An in vitro biofilm study

Publication date: Available online 29 November 2018

Source: Dental Materials

Author(s): M.C. Sánchez, M. Toledano-Osorio, J. Bueno, E. Figuero, M. Toledano, A.L. Medina-Castillo, R. Osorio, D. Herrera, M. Sanz

Abstract

Objective

to study the antibacterial effect of polymeric PolymP-n Active nanoparticles using an in vitro subgingival biofilm model.

Methods

Hydroxyapatite discs coated with five modalities of nanoparticles (NPs): NPs, NPs doped with zinc, calcium, silver and doxycycline, PBS as control, and Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were studied in a static in vitro biofilm model (12, 24, 48, and 72 h). Nano-roughness of the different disc surfaces (SRa, in nm) and morphological characteristic of the biofilms (thickness (μm) and bacterial viability) were studied by different microscopy modalities. Quantitative Polymerase Chain Reaction was used to assess the effect of the nanoparticles on the bacterial load (colony forming unit per milliliter) (CFU mL⁻¹). Analysis of variance and post-hoc testing with T3 Dunnett́s, and Student Newman Keuls correction was used. Results were considered statistically significant at p < 0.05.

Results

Surfaces containing the different nanoparticles showed significant increments in roughness when compared to controls (p < 0.05). A similar biofilm formation and dynamics was observed, although reductions in bacterial viability were detected in biofilms in contact with the different nanoparticles, more pronounced with silver and doxycycline NPs. Doxycycline-NPs biofilms resulted in unstructured biofilm formation and significantly lower number of the six species when compared with the other nanoparticles specimens and controls (p < 0.001 in all cases).

Significance

Polymeric PolymP-n Active nanoparticles when combined with silver and doxycycline showed a significant antibacterial effect when tested in an in vitro subgingival biofilm model.

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Physical properties and cytotoxicity of antimicrobial dental resin adhesives containing dimethacrylate oligomers of Ciprofloxacin and Metronidazole

Publication date: Available online 29 November 2018

Source: Dental Materials

Author(s): Yasaman Delaviz, Timothy W. Liu, Ashley R. Deonarain, Yoav Finer, Babak Shokati, J. Paul Santerre

Abstract

Objective

Antimicrobial oligomers synthesized from ciprofloxacin (CF) and metronidazole (MN) were investigated for their potential use in dental adhesives.

Methods

Susceptibility of the cariogenic bacterium Streptococcus mutans UA159 to CF, MN, and CF/MN combination was evaluated. Hydrolytic stability and drug release from the oligomers was studied in buffer and simulated human salivary esterase conditions. Cytotoxicity of films with 15 wt% drug oligomers co-polymerized with commercial monomers were assessed using human gingival fibroblasts (HGFs). In-house adhesives were prepared and characterized for viscosity. Polymerized films were analysed for gel content and water swelling. Interfacial fracture toughness (K_IC) of composites bonded to dentin by either a 2 or 3-step etch-and-rinse approach using the in-house formulated adhesives was measured.

Results

The respective minimum inhibitory concentration for CF and MN against S. mutans was 0.7 and 2400 μg/mL, with the combination having an additive effect (0.35 μg/mL CF with 1200 μg/mL MN). Antibiotics were released upon hydrolysis of the oligomers. Films containing the drug oligomers were not cytotoxic against HGFs. Replacing 2-hydroxyethyl methacrylate with the drug oligomers increased the viscosity of the experimental adhesives, reduced gel content, and decreased swelling of films in water. Antimicrobial adhesives demonstrated bonding to dentin with interfacial K_IC values comparable to the in-house control in the 2-step application, and with slightly lower K_IC values in the 3-step approach.

Significance

The antimicrobial oligomers can be incorporated into dental adhesive systems using formulations that show comparable fracture toughness to commercial materials, and may provide a means to deliver local antimicrobial drug release at the marginal interface.

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Positive correlation between fluoride release and acid erosion of restorative glass-ionomer cements

Publication date: Available online 29 November 2018

Source: Dental Materials

Author(s): Lígia S. Bueno, Rafael S. Menezes, Ana Paula R. Magalhães, Maria Fidela L. Navarro, Renata C. Pascotto, Marília A.R. Buzalaf, Sharanbir K. Sidhu, John W. Nicholson, Ana Flávia S. Borges

Abstract

Objective

The aim of this study was to determine whether there is a correlation between acid erosion and fluoride release of conventional glass ionomer cements.

Methods

Ten specimens for each material were prepared for fluoride release tests and five for acid erosion tests separately. After placed in pH cycling solution, concentration of fluoride was measured by a fluoride-ion selective electrode each day for 15 days. For the acid erosion test, specimens were immersed in a lactic acid solution and their depth measured with a spring-loaded dial gauge. The data were submitted to 3-way ANOVA, followed by Tukey's test (p < 0.05)

Results

All materials showed ability to elute fluoride in the 15 day period of the test, with the same pattern of high fluoride release at the first 24 h. Despite this, the amount of fluoride released was statistically different among the 18 groups, with the highest for Maxxion R and the lowest for Chemfil Rock (p > 0.05). The highest acid erosion values were registered for Magic Glass, Ion Z, VitroFil and Maxxion R, which exceeded the maximum stipulated by the relevant ISO test (ISO 9917-1). A positive linear correlation (r² = 0.4886) was found for both properties, i.e., higher fluoride release is related to higher acid erosion.

Significance

Acid erosion and fluoride release are related properties of GICs, though factors such as pH and P/L ratio lead to differences between actual values for individual brands of these materials.

Graphical abstract

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PET/TC con 18F-FDG «superscan» en paciente con linfoma inmunoblástico

Publication date: Available online 30 November 2018

Source: Revista Española de Medicina Nuclear e Imagen Molecular

Author(s): I. Acevedo-Báñez, Á. De-Bonilla-Damiá, R. Fernández-López

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

Publication date: Available online 30 November 2018

Source: Journal of Voice

Author(s): Maxine Van Doren, Elizabeth Faudoa, Thomas L. Carroll

Abstract

Objective

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.

Methods/Design

Retrospective review. Subjects included demonstrated subtle glottic insufficiency from true vocal fold atrophy and comorbid EVT with no other vocal fold pathology. Voice Handicap Index (VHI-10), aerodynamic data including subglottic pressure and airflow, and the tremor scoring scale were evaluated before diagnostic VFIA with carboxymethylcellulose and after durable VFIA with calcium hydroxylapatite or autologous fat.

Results

Seven patients met inclusion criteria. Six subjects went on to durable VFIA. Three of six demonstrated meaningful improvement in the VHI-10 score. Subglottic pressure improved significantly in those subjects with meaningful VHI-10 improvement compared to those that did not. The tremor did not resolve completely in any subject, but patient satisfaction and function was improved in four of the six.

Conclusions

VFIA for EVT in the setting of true vocal fold atrophy appears to offer benefit and may be an alternative treatment pathway for EVT patients. More than half of the subjects who underwent durable VFIA after successful diagnostic VFIA reported improvement in their communication despite inconsistent objective outcomes. Subglottic pressure improved significantly in half of the subjects who also reported a substantive improvement in their VHI-10.

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Biobehavioral Measures of Presbylaryngeus

Publication date: Available online 30 November 2018

Source: Journal of Voice

Author(s): Vrushali Angadi, Colleen McMullen, Richard Andreatta, Maria Dietrich, Tim Uhl, Joseph Stemple

Abstract

Objective

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

Study design

Cross-sectional study.

Methods

Participants 60–85 years of age were divided into two age and sex-matched groups, based on the presence or absence of presbylaryngeus. Both groups underwent a battery of tests measuring anthropometric variables, inflammatory markers, general health measures, and vocal function parameters. Differences from the norm were calculated for all variables. Parametric and nonparametric tests were performed to assess group differences. In addition, variable selection analysis was performed to determine variables that were most influential in predicting the occurrence of presbylaryngeus in our current sample.

Results

Fifty-three participants were divided into age and sex-matched groups of "presbylaryngeus" (n = 26) and "non-presbylaryngeus" (n = 27). The two groups were statistically different in select measures of inflammatory markers, general health measures, and vocal function parameters. Anthropometric measures were not statistically different. Based on variable selection, the variables most predictive of the presence of presbylaryngeus were measures of the Physical Activity Scale of the Elderly, C-reactive protein, laryngeal airway resistance, and vocal roughness.

Conclusions

In addition to group differences in vocal function measures, results for the presbylaryngeus group consistently trended sub-optimally on anthropometric measures, two inflammatory markers, and general health measures. These results suggest that this sample of individuals with presbylaryngeus demonstrated greater biobehavioral deficits associated with aging as compared to age and sex-matched non-presbylaryngeus individuals.

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Challenges in allergy immunology practice: Solutions needed for persistent patient problems

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s): Gailen D. Marshall

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Author Index

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

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A new acronym for PPI-REE?

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s): Russell Hopp

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Editorial Board

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s):

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Information for Authors

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s):

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Table of Contents

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s):

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Information for Readers

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s):

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Erratum

Publication date: December 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 6

Author(s):

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

Publication date: Available online 29 November 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): C.P. Harkins, M.T.G. Holden, A.D. Irvine

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Individual 3-dimensional printed mold for treating hard palate carcinoma with brachytherapy: A clinical report

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Valentina Lancellotta, Stefano Pagano, Luca Tagliaferri, Marco Piergentini, Alessandro Ricci, Sandro Montecchiani, Simonetta Saldi, Sara Chierchini, Stefano Cianetti, Vincenzo Valentini, György Kovács, Cynthia Aristei

Abstract

This clinical report describes the use of a 3-dimensional (3D) printer to create an individual mold for delivering high-dose-rate interventional radiotherapy for hard palate cancer. The maxillary teeth and palate were scanned with an intraoral scanner (3Shape Trios 3). The scan was transformed into a mesh using the standard tessellation language (STL) format and aligned with Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) images using free Blue Sky Plan 4 planning software. A mold was generated by tracing a guideline around the gingival margins of the maxillary teeth and palate on the scan mesh in accordance with established parameters. All data were imported into computer-aided design (CAD) software. For this patient, 3 parallel 2.2-mm-diameter ducts were placed 10 mm from each other in the mold mesh. A CT scan of the patient's mouth with the mold in place was used for treatment planning. Treatment was delivered by means of microSelectron digital afterloading.

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Prosthodontic treatment of a patient with Ewing sarcoma of the left maxillary sinus: A clinical report

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Woo J. Chi, Matthew M. Hanasono, Theresa M. Hofstede, Ruth A. Aponte-Wesson

Abstract

This clinical report describes the prosthodontic rehabilitation of a 22-year-old woman with a substantial treatment history of Ewing sarcoma of the left maxillary sinus. The patient was diagnosed with Ewing sarcoma at the age of 7 years and went through chemotherapy, radiation, surgical resection, and free-flap reconstruction, initially without prosthodontic rehabilitation. The patient aged 22 years was referred to the oral oncology clinic at The University of Texas MD Anderson Cancer Center for prosthodontic treatment. The patient's prosthetic rehabilitation with dental implants and a definitive maxillary obturator prosthesis is presented in detail.

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Color stability of maxillofacial prosthetic silicone functionalized with oxide nanocoating

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Arghya Kamal Bishal, Alvin G. Wee, Valentim A.R. Barão, Judy Chia-Chun Yuan, Richard Landers, Cortino Sukotjo, Christos G. Takoudis

Abstract

Statement of problem

Maxillofacial prostheses made of silicone elastomers undergo undesirable color degradation over time. How this color change can be prevented is unclear.

Purpose

The purpose of this in vitro study was to evaluate the ability of an oxide nanocoating to prevent color degradation of maxillofacial silicone elastomers after artificial accelerated aging.

Material and methods

A silicone elastomer with functional intrinsic pigment was tested. Specimens (N=20) were fabricated, and half of them were coated with a nanolayer of titanium dioxide (TiO₂) using atomic layer deposition. Both coated and noncoated specimens (control) were exposed to artificial aging at 450 kJ/m² of total energy. Changes in the color of all the specimens with and without TiO₂ nanocoating were measured before and after the atomic layer deposition coating and before and after aging. The obtained color data were analyzed by using independent t tests and the 1-sample t test (α=.05).

Results

Color change (ΔE1=3.4 ±1.4) was observed for the silicone elastomers after the specimens were surface coated with TiO₂ nanofilm, although this change was not statistically significant (P=.369) compared with the acceptability threshold (ΔE=3.0). Upon exposure to artificial aging, the noncoated control specimens underwent color change (ΔE2=2.5 ±0.7, P=.083 compared with the acceptability threshold). The specimens with TiO₂ nanocoated surface experienced the least color change (ΔE3=1.4 ±0.6) when subjected to artificial aging, and this change was significantly lower (P<.001) than the established acceptability threshold of ΔE=3.0. In addition, the chemical analyses confirmed that the TiO₂ nanocoating remained on the surface after exposure to artificial aging.

Conclusions

TiO₂ nanocoating was shown to be effective in reducing color degradation of the silicone elastomer exposed to artificial aging for 120 hours with 450 kJ/m² of total energy.

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Clinical remounting of complete dentures: A systematic review

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Tyler V. Verhaeghe, Bernie A. Linke, Cheryl E. Cable, Nesrine Mostafa

Abstract

Statement of problem

A recent trend has been to reduce the procedural complexity of complete denture fabrication. Whether the clinical remount step is necessary is unclear.

Purpose

The purpose of this systematic review was to assess the relevance of the clinical remount procedure on complete denture outcomes.

Material and methods

Five electronic databases were searched through to May 2018. The terms "denture*", "dental prosthes*", "equilibrat*", and "remount*" were chosen. The titles and abstracts were screened, and those which met the inclusion criteria were selected for full-text assessment. Studies that only performed the laboratory remount or were not randomized controlled studies were excluded.

Results

After duplicate removal, the database search strategy resulted in a total of 226 potential studies. After the titles and abstracts had been screened and the inclusion and exclusion criteria applied, 10 studies were retrieved for full-text assessment. Four randomized controlled clinical studies were included in the systematic review. A meta-analysis could not be performed because of variation in outcome measures after the clinical remount.

Conclusions

A clinical remount for complete dentures is recommended on delivery to reduce clinically observed areas of discomfort and reduce the number of recall appointments. The development of a reliable and valid patient satisfaction questionnaire is necessary to determine conclusively whether the clinical remount also improves patient-perceived satisfaction and mastication.

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Is predicting masticatory function based on mandibular bone atrophy as defined by clinical and radiographic parameters possible? A clinical study

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Alessandra Julie Schuster, Raissa Micaella Marcello-Machado, Amália Machado Bielemann, Luciana de Rezende Pinto, Fernanda Faot

Abstract

Statement of problem

The degree of mandibular bone atrophy can guide and determine the choice of prosthetic treatment. Although several methodologies have been proposed for classifying atrophy, the clinical and radiographic parameters considered for the classification of mandibular bone atrophy should be standardized.

Purpose

The purpose of this clinical study was to evaluate the influence of methodologies of mandibular bone atrophy categorization on the masticatory function in complete denture (CD) wearers and to verify the relationship between these parameters according to the retention and stability of the mandibular CD.

Material and methods

CD wearers were radiographically and clinically evaluated to determine the mandibular bone atrophy levels. Three classifications were adopted: the Cawood and Howell criteria, the Wical and Swoope criteria, and the Kapur classification. CD retention and stability were scored based on the Sato et al method. The masticatory function was evaluated by the multiple sieve method using optical test food to determine the masticatory performance (MP) indexes (median particle size, MP X50; homogeneity index, MP B) and the masticatory efficiency (sieves 4 and 2.8).

Results

In this sample of 63 individuals (mean age of 67.4 years), atrophic participants presented significant differences in all radiographic parameters (Mann–Whitney test, P<.05) with both the Cawood and Howell and Wical and Swoope methodologies. No differences in masticatory function were found, except for atrophic participants classified by Wical and Swoope criteria, who had worse MP X50 (P=.047) than nonatrophic participants, with a medium effect size of 0.7. The retention of the mandibular CD significantly affected the masticatory outcomes, with higher values for MP X50 (P=.012) and MP B (P=.040) and lower values for masticatory efficiency, 2.8 (P=.008) for atrophic participants. The presence of mandibular bone atrophy showed an association with poor retention (P=.04) and poor stability (P=.002) when the Cawood and Howell criteria were adopted (Fisher exact test, P<.05).

Conclusions

The Kapur classification confirmed the clinical condition of the participants' atrophy, and the most clinically atrophic participants showed poor retention and stability of the mandibular CD. Only the poor retention directly affected the masticatory function. Radiographic evaluations alone did not provide sufficient data to determine the predictability of CD treatment regarding the participants' masticatory function. Radiographically, atrophic participants with poor retention had impaired mastication.

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Trephination-based, guided surgical implant placement: A clinical study

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Nawakamon Suriyan, Lertrit Sarinnaphakorn, George R. Deeb, Sompop Bencharit

Abstract

Statement of problem

Conventional guided implant surgery promises clinical success through implant placement accuracy; however, it requires multiple drills along with surgical sleeves and sleeve adapters for the horizontal and vertical control of osteotomy drills. This results in cumbersome surgery, problems with patients having limited mouth opening, and restriction to specific drill or implant manufacturers. A protocol for using trephination drills to simplify guided surgery and accommodate multiple implant systems is introduced.

Purpose

The purpose of this clinical study was to evaluate the accuracy of implant placement using this novel guided trephine drill protocol with and without a surgical sleeve.

Material and methods

Intraoral scanning and preoperative cone beam computed tomography (CBCT) scans were used for implant treatment planning. Surgical guides were fabricated using stereolithography. Implant surgery was performed using the guided trephination protocol with and without a surgical sleeve. Postoperative CBCT scans were used to measure the implant placement deviations rather than the implant planning position. Surgical placement time and patient satisfaction were also documented. One-tailed t test and F-test (P=.01) were used to determine statistical significance.

Results

Thirty-five implants in 17 participants were included in this study. With a surgical sleeve, implant positional deviations were 0.51 ±0.13 mm vertically, 0.32 ±0.10 mm facially, 0.11 ±0.11 mm lingually, and 0.38 ±0.13 mm mesially. Without a surgical sleeve, implant positional deviations were 0.58 ±0.27 mm vertically, 0.3 ±0.14 mm facially, 0.39 ±0.16 mm lingually, and 0.41 ±0.12 mm mesially. No statistically significant difference was found between the 2 protocols (P>.01), except that the sleeve group had greater vertical control precision (F-test, P=.006), reduced placement time, and the time variation was reduced (t test, P=.003; F-test, P<.001).

Conclusions

This trephination-based, guided implant surgery protocol produces accurate surgical guides that permit guided surgery in limited vertical access and with the same guided surgery protocol for multiple implant systems. Guided sleeves, although not always necessary, improve depth control and reduce surgical time in implant placement.

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Satisfaction of patients with amyotrophic lateral sclerosis with an oral appliance for managing oral self-biting injuries and alterations in their masticatory system: A case-series study

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Nina Riera-Punet, Jordi Martinez-Gomis, Carla Zamora-Olave, Eva Willaert, Maria Peraire

Abstract

Statement of problem

About 10% of patients with amyotrophic lateral sclerosis (ALS) are candidates for oral treatment specifically because of traumatic injuries in the lips, cheeks, or tongue due to self-biting. However, patients with ALS have a prevalence of temporomandibular disorder (TMD) similar to that in the general population.

Purpose

The purpose of this case-series study was to determine the degree of satisfaction of patients with ALS with an oral appliance for managing oral self-biting lesions or symptoms related to TMDs. This study also assessed the degree of improvement of the chief complaint and the compliance with and adverse effects of this treatment.

Material and methods

Eleven patients with ALS who sought oral treatment because of oral self-biting or TMD-related symptoms were included. A custom complete-coverage acrylic resin device was fabricated and fitted to each participant. A follow-up visit was planned for 3 months after the placement of the oral appliance, at which point the patients would rate the degree of improvement or worsening of the chief complaint and their degree of satisfaction with the treatment. A 1-sample t test was used to assess whether the degree of improvement of the chief complaint was significant.

Results

Participants reported a mean of 61% (95% confidence interval [CI] 38% to 84%) improvement of the chief complaint and a mean of 84% (95% CI 72% to 97%) satisfaction with the treatment. The mean rate of compliance was 62% (95% CI 40% to 84%) of the recommended time, and only a few adverse effects were reported.

Conclusions

Participants with ALS were highly satisfied with the use of an oral appliance to manage oral self-biting or TMD-related symptoms. Adherence to this treatment was high, and no major adverse effects were observed.

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Fabricating a low-cost autoclavable throat screen from a steamer mat

Publication date: Available online 30 November 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Ram Prakash, Krishna Prakash

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Quantitative Assessment of Bladder Cancer Reflects Grade and Recurrence: Comparing of Three Methods of Positioning Region of Interest for ADC Measurements at Diffusion-weighted MR Imaging

Publication date: Available online 30 November 2018

Source: Academic Radiology

Author(s): Hongyi Li, Lin Liu, Lei Ding, Zhenming Zhang, Mengchao Zhang

Purpose

To determine the impact of three different regions of interests (ROIs) positioning methods for apparent diffusion coefficient (ADC) measurements on the assessment of the grade and recurrence and to examine the correlation between ADC value and histopathological grade/ Ki-67 labeling index (LI) in patients with bladder cancer.

Materials and Methods

Sixty-one patients with bladder cancer were retrospectively evaluated. Two observers measured mean ADC values using whole-volume-ROIs, single-section-ROI and three-ROIs methods. Interclass correlation coefficient was analyzed to assess interobserver variability. The grade and recurrence in patients with bladder cancer were assessed by calculating the areas under the receiver operating characteristic curves with Az values. Spearman's correlation was used to analyze the correlations of ADC value with grade and Ki-67 LI.

Results

For the mean ADC value, the interclass correlation coefficient were excellent with the whole-volume and the single-section method (0.90 [95% CI: 0.84, 0.94] and 0.89 [95% CI: 0.81, 0.93]) and was good with the three-ROIs method (0.72 [95% CI: 0.53, 0.83]). The Az value for determining histological grade and recurrence of bladder cancer were not significantly different from each positioning method (all p > 0.05). There's significant correlation between histological grade and ADC measuring by whole-volume-ROIs and single-section-ROI methods (r = 0.31, p = 0.02; r = 0.37, p < 0.05). The ADC measured by whole-volume-ROIs, single-section-ROI, and three-ROIs methods were significantly and inversely correlated with the Ki-67 LI (r = −0.3; r = −0.49; r = −0.40, all p < 0.05).

Conclusion

There's no significant difference among any of the ROI positioning methods in evaluation of tumor grade and recurrence. There's significant correlation between histological grade and ADC measuring by whole-volume-ROIs and single-section-ROI methods. The ADC value obtained by either of three methods was significantly and inversely correlated with the Ki-67 LI.

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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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