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Tuesday, December 11, 2018

Correction to: Anatomical locations in the oral cavity where surgical resections of oral squamous cell carcinomas are associated with a close or positive margin—a retrospective study

The following note was inadvertently omitted from the published paper: This work was performed in (partial) fulfillment of the requirements for the first author's obtaining the degree Dr. med. dent.



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Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging

Abstract

Purpose

Quantitative susceptibility mapping (QSM) is influenced by iron as well as myelin, which makes interpretation of pathologic changes challenging. Concurrent acquisition of MR sequences that are sensitive to axonal/myelin integrity, such as diffusion tensor imaging (DTI), may provide context for interpreting quantitative susceptibility (QS) signal. The purpose of our study was to investigate alterations in normal-appearing white matter (NAWM) in multiple sclerosis (MS) using QSM in conjunction with DTI.

Methods

Twenty relapsing–remitting MS patients and 20 age-matched healthy controls (HC) were recruited for this prospective study. QS, radial diffusivity (RD), fractional anisotropy (FA), and R2* maps within the whole brain as well as individual tracts were generated for comparison between NAWM and HC white matter (HCWM).

Results

MS lesions demonstrated significant differences in QS, FA, RD, and R2* compared to HCWM (p < 0.03). These metrics did not show a significant difference between whole-brain NAWM and HCWM. Among NAWM tracts, the cingulate gyri demonstrated significantly decreased QS compared to HCWM (p = 0.004). The forceps major showed significant differences in FA and RD without corresponding changes in QS (p < 0.01).

Conclusion

We found discordant changes in QSM and DTI metrics within the cingulate gyri and forceps major. This may potentially reflect the influence of paramagnetic substrates such as iron, which could be decreased along these NAWM tracts. Our results point to the potential role of QSM as a unique biomarker, although additional validation studies are needed.



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A mathematical approach improves the predictability of length of hospitalization due to acute odontogenic infection: A retrospective investigation of 303 patients

Increasing rates of hospitalization of patients diagnosed with acute odontogenic infection have become a burden for public health care, with significant economic concerns. The aim of this study was to investigate factors that tend to prolong hospital length of stay (LOS) in the treatment of severe infections. We present a statistical model that enables the prediction of LOS by exposing the feasibility of the essential statistical determinants.

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Reliability and intra-examiner agreement of orthodontic model analysis with a digital caliper on plaster and printed dental models

Abstract

Objective

To investigate if orthodontic model analysis with a digital caliper can be interchangeably performed between plaster and printed dental models.

Materials and methods

Forty-eight plaster models were digitized with orthoX®scan (DENTAURUM) and 48 counterparts were printed with Objet30 Dental Prime (Stratasys). One examiner performed five repeated orthodontic model analyses (41 outcomes) with a digital caliper in each plaster and the corresponding printed model and was externally validated by a second examiner. Inter- and intra-examiner reliability and error were evaluated with intraclass correlation coefficients (ICCs) and Dahlberg's formula, intra-examiner agreement with Bland-Altman analyses and Lin's correlation coefficients (CCCs), and changing bias with regression analyses.

Results

Inter- and intra-examiner ICCs and Dahlberg's error were ≥ 0.75 and ≤ 0.5 mm, respectively, for most outcomes in both plaster and printed models. Intra-examiner agreement (systematic bias) between plaster and printed models ranged from − 0.45 to 0.45 mm. Ranges of limits of agreement were wide for cumulative outcomes, such as crowding maxilla and mandible (2.69 mm and 3.07 mm around zero, respectively). Tooth widths were measured slightly larger in printed models. Lin's CCCs were ≥ 0.87 for all the outcomes between plaster and printed models, while no changing bias was detected.

Conclusion

If orthodontic model analyses are consistently performed, plaster casts and their corresponding printed models obtained with orthoX®scan and Objet30 Dental Prime can be interchangeably used for clinical purposes in orthodontics.

Clinical relevance

Orthodontic model analysis is important in treatment planning and printed dental models need to be validated regarding this diagnostic procedure.



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The role of the skin microbiome in atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease associated with significant medical burden, affecting 15-20% of children and 1-3% of adults worldwide.1 The prevalence of AD has increased by 2-3 folds during the past decade in Western countries. While the cause of this increase remains unknown, meta-analyses have indicated that the risk of AD is lower when associated with potentially protective environmental factors during childhood such as three or more siblings, day care, pet ownership and farm residence.

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The Asthma Controller Step-down Yardstick

Guidelines for asthma recommend a series of treatment steps (Figure 1) as a framework for disease management.1,2 The steps allow individualized adjustments in controller therapy in an upward or downward manner in response to a patient's level of asthma control over a period of time. For patients with inadequately controlled asthma, a step-up is recommended.1,2 Strategies for stepping up controller therapy are described in detail in the adult and pediatric Asthma Yardsticks.3,4 For patients whose asthma has been well controlled for at least 3 months (or longer for the highest risk patients), controller treatment may be stepped down.

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Cytokine levels in crevicular fluid associated with compliance during periodontal maintenance therapy

Abstract

Objectives

To longitudinally evaluate the effects of compliance during periodontal maintenance therapy (PMT) on cytokines levels and its relation to periodontal status.

Materials and methods

Ninety-one eligible individuals were selected from a 6-year prospective study with 212 individuals in PMT. From this total, 28 regular compliers (RC) were randomly selected and matched for age and gender with 28 irregular compliers (IC). All participants were non-smokers and non-diabetic. Periodontal parameters and gingival crevicular fluid samples were collected in 5 times: T1 [prior to active periodontal therapy (APT)], T2 (after APT), T3 (2 years), T4 (4 years), and T5 (6 years). Levels of IL-6, IL-10, IL-1β, TNF-α, and MMP-8 were quantified through ELISA.

Results

RC presented better clinical periodontal status over time when compared to IC. A significant reduction in the levels of IL-1β, TNF-α, MMP-8, and IL-6 was observed among RC along time (from T1 to T5). Levels of IL-1 were similar among groups. By contrast, levels of IL-6 and TNF-α increased over time in IC individuals. Levels of IL-10 increased among RC and reduced among IC.

Conclusions

The inflammatory cytokines IL-1, TNF-α, IL-6, and MMP-8 were correlated with worse clinical parameters among IC, while IL-10 was associated with an improvement in clinical parameters among RC. These results reinforce the role of these cytokines in the pathogenesis of periodontitis, as well as their role as markers to monitoring the progression of the periodontitis.

Clinical relevance

Regular compliance during 6-year period the PMT sustained clinical and immunological benefits obtained after active periodontal therapy.



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Estrogen receptor gene is associated with dental fluorosis in Brazilian children

Abstract

Objectives

The aim of this study was investigate the association between genetic polymorphisms in ESR1, ESR2, and ESRRB and dental fluorosis (DF) in a well-characterized sample of children from Curitiba, Brazil.

Material and methods

From a representative sample of 538 children, 12-year-old were evaluated. DF was assessed in erupted permanent teeth by the Dean's index modified. Fourteen polymorphisms were selected in intronic and intergenic regions of ESR1, ESR2, and ESRRB and genotyped in genomic DNA source from saliva using TaqMan chemistry and end-point analysis. Allele and genotype distributions between DF and DF free groups were analyzed using the Epi Info 7.2. Chi-square or Fisher's exact tests at a level of significance of 5% and odds ratios calculations with 95% confidence intervals were used to determine the statistical associations.

Results

Among 538 children, 147 were DF and 391 were DF free. Genotype distribution for the polymorphism rs12154178 in ESR1 was different between the two groups (p = 0.037; OR = 0.91; CI = 0.67–1.22). The dominant model analysis (AA+AC vs. CC) demonstrated that CC is a protective factor for DF (p = 0.038; OR = 0.51, 0.27–0.97 95% CI). We did not find differences in frequency distributions in the other evaluated polymorphisms.

Conclusion

This study provides evidence that ESR1 is associated with DF.

Clinical relevance

Dental fluorosis is an important condition that affects the mineralized tissues of the teeth. In severe cases, the treatment takes time and is extremely costly. This research provides evidences that there are genetic factors involved in dental fluorosis and will help professionals to plan more precise strategies to reduce dental fluorosis occurrence.



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Clinical evaluation of direct pulp capping using a calcium silicate cement—treatment outcomes over an average period of 2.3 years

Abstract

Objectives

This study aims to assess the treatment outcomes of direct pulp capping with a calcium silicate cement (Biodentine) after caries excavation.

Materials and methods

A total of 245 teeth of 226 patients diagnosed to be clinical healthy or showing spontaneous pain were directly capped. The teeth were examined 0.19 to 7.4 (mean 2.3 ± 2.04) years after treatment. The following data were recorded: age and sex of the patient, type of tooth and restoration (glass ionomer cement [GIC], amalgam, composite resin, ceramic, gold) and symptoms before or after treatment. The evaluation of the treatment was carried out by sensibility and percussion testing and by the patient's questioning. A positive sensibility test, a negative percussion test, the absence of swelling and discomfort were considered as treatment success. Survival analysis was performed using the Kaplan-Meier, log-rank, Chi-square and Fisher's exact test, respectively.

Results

After an average period of 2.3 years, 86.0% of the teeth remained vital; the survival rate after 7.4 years was 83.4%. The treatment outcome was significantly worse for cavities restored with GIC compared to all other restorative materials (p < 0.05). All other evaluated factors had no significant influence on the success rate (p > 0.05).

Conclusion

Exposed pulps of asymptomatic vital permanent teeth and teeth with spontaneous pain before treatment can be successfully capped directly using Biodentine. A subsequent restoration with GIC does not appear to be suitable as it significantly reduces the success of the treatment.

Clinical relevance

Direct pulp capping can be done successfully with this type of calcium silicate cement.



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Anticaries effect of toothpaste with nano-sized sodium hexametaphosphate

Abstract

Objective

To evaluate the effect of a fluoride toothpaste containing nano-sized sodium hexametaphosphate (HMPnano) on enamel demineralization on the biochemical composition and insoluble extracellular polysaccharide (EPS) in biofilm formed in situ.

Methods

This crossover double-blind study consisted of four phases (7 days each), in which 12 volunteers wore intraoral appliances containing four enamel bovine blocks. The cariogenic challenge was performed using 30% sucrose solution (6×/day). Blocks were treated 3×/day with the following toothpastes: no F/HMP/HMPnano (Placebo), conventional fluoride toothpaste, 1100 ppm F (1100F), 1100F + 0.5% micrometric HMP (1100F/HMP), and 1100F + 0.5% nano-sized HMP (1100F/HMPnano). The percentage of surface hardness loss (%SH), integrated loss of subsurface hardness (ΔKHN), and enamel calcium (Ca), phosphorus (P), and fluoride (F) were determined. Moreover, biofilms formed on the blocks were analyzed for F, Ca, P, and insoluble extracellular polysaccharide (EPS) concentrations. Data were analyzed using one-way ANOVA, followed by Student–Newman–Keuls' test (p < 0.001).

Results

1100F/HMPnano promoted the lowest %SH and ΔKHN among all groups (p < 0.001). The addition of HMPnano to 1100F significantly increased Ca concentrations (p < 0.001). The 1100F/HMPnano promoted lower values of EPS when compared with 1100F (~ 70%) (p < 0.001) and higher values of fluoride and calcium in the biofilms (p < 0.001).

Conclusion

1100F/HMPnano demonstrated a greater protective effect against enamel demineralization and on the composition of biofilm in situ when compared to 1100F toothpaste.

Clinical relevance

This toothpaste could be a viable alternative to patients at high risk of caries.



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Identification of salivary metabolites for oral squamous cell carcinoma and oral epithelial dysplasia screening from persistent suspicious oral mucosal lesions

Abstract

Objective

To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with persistent suspicious oral mucosal lesions (PSOML).

Subjects and methods

Whole unstimulated saliva samples were collected from age-, sex-, and race-matched patients who had a lesion in the oral cavity and for whom open biopsies were performed. The patients included OSCC (n = 6), OED (n = 10), and PSOML (n = 32). Hydrophilic metabolites in saliva samples were comprehensively analyzed using capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC/OED from PSOML.

Results

Six metabolites were significantly different in OSCC/OED compared with PSOML. From these six metabolites, ornithine, o-hydroxybenzoate, and ribose 5-phosphate (R5P) were used to develop the MLR model, which resulted in a high value for the area under receiver operating characteristic curve (AUC 0.871, 95% confidential interval (CI) 0.760–0.982; p < 0.001) to discriminate OSCC/OED from PSOML.

Conclusions

This is the first study to identify salivary metabolites that discriminate OSCC/OED from PSOML rather than from healthy controls. The profiles of salivary metabolites were significantly different between OSCC/OED and PSOML. The ability to discriminate OSCC/OED from PSOML is important for dentists who are not oral surgery specialists. These salivary metabolites showed potential for non-invasive screening to discriminate OSCC/OED from PSOML.

Clinical relevance

Salivary metabolites in this study showed potential for non-invasive screening to discriminate OSCC/OED from PSOML.



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Resident Education in Laryngeal Stroboscopy and Perceptual Voice Evaluation: An Assessment

Publication date: Available online 10 December 2018

Source: Journal of Voice

Author(s): Joel W. Jones, Mollie Perryman, Paul Judge, Maraya M. Baumanis, Kevin Sykes, Jayme Dowdall, Cristina Cabrera-Muffly, James David Garnett, Shannon Kraft

Summary
Objectives

To evaluate otolaryngology residents' level of confidence and understanding in interpreting laryngeal stroboscopy.

Methods

Otolaryngology residents from three residency programs with fellowship-trained laryngologists on faculty were invited to participate. An assessment consisting of a survey and five stroboscopic exams was administered. Each exam consisted of questions on perceptual voice evaluation, laryngoscopic findings, and stroboscopic findings. Scores were compared to answers provided by three fellowship-trained laryngologists.

Results

Thirty-eight of 47 invited residents (80.8%) enrolled in the study. On a five-point likert scale, residents reported low confidence (median = 2, range = 1–4) in interpreting stroboscopy, regardless of training program (P = 0.81). Mean assessment scores were 56.5% ± 11.9, with scores in perceptual voice evaluation = 68.5% ± 10.6; laryngoscopy = 70.2% ± 12.8; and stroboscopy = 45.3% ± 17.8. Residents performed worse on stroboscopy questions compared to laryngoscopy questions (P < 0.0001). There was a significant difference in scores by postgraduate year (P = 0.03), but not by institution (P = 0.34). A moderately positive correlation between reported level of confidence and overall scores (ρ = .47, P = 0.003) was demonstrated.

Conclusions

Despite didactic and clinical exposure, residents report low confidence in interpreting stroboscopy and scored lower on stroboscopy-specific questions compared to other assessment items. Additional resources and learning opportunities are needed to improve resident confidence and comprehension of stroboscopy.



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News and Notes

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s):



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Impact of crestal bone resorption on quality of life and professional maintenance with conventional dentures or Locator-retained mandibular implant overdentures

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s): Carine Matthys, Stijn Vervaeke, Wolfgang Jacquet, Hugo De Bruyn

Abstract
Statement of problem

The influence of the mandibular resorption profile on clinical outcome after converting a conventional complete denture into a Locator-retained implant overdenture is unknown.

Purpose

The purpose of this prospective study was to assess the oral health-related quality of life (OHRQoL) and prosthetic maintenance of mandibular overdentures on 2 Locator abutments in relation to the resorption degree of the edentulous mandible.

Material and methods

Twenty-five participants were treated and classified according to the Cawood and Howell (CAW-H) resorption classification for the resorption profile of the mandible, CAW-H group III-IV (n=14) and CAW-H group V (n=11). Participants received conventional complete dentures (CDs) before implant placement and immediate nonfunctional loading on Locators with a resilient liner. After 3 months, the attachments were functionally activated. Assessments were made using the Oral Health Impact Profile 14 (OHIP-14) questionnaires with existing CDs and new CDs at 1, 3, and 15 months after loading. Prosthetic maintenance (repairs, rebasings, replacement of retention parts) and biological prosthetic aftercare were assessed. For comparison between groups, the Kruskal-Wallis and Mann-Whitney U tests were applied for continuous and ordinal variables and the chi-square test for cross-tabulations. To analyze repeated OHIP-14 scores, the Friedman test was used for ordered alternatives to test whether the measurements differed (overall significance level α=.05). Then the Wilcoxon signed rank test was conducted to detect specific differences (α=.05).

Results

OHIP-14 scores decreased significantly after implant placement and functional connection for the whole population (P<.001) and for both sub groups, the CAW-H group III-IV (P<.001) and the CAW-H group V (P=.013). CAW-H group V participants needed more retention inserts than CAW-H group III-IV participants (26 versus 3, respectively; P=.006). The incidence of repair and rebasing was limited for both groups, and biological aftercare and pain relief were comparable.

Conclusions

Changing a CD to an overdenture significantly improved ORLQoL regardless of the resorption degree, but heavily resorbed mandibles require more replacements of retention inserts.



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Sponsoring Organizations and Liaisons

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s):



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Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s): Terence E. Donovan, Riccardo Marzola, Kevin R. Murphy, David R. Cagna, Frederick Eichmiller, James R. McKee, James E. Metz, Jean-Pierre Albouy, Mathias Troeltzsch

Abstract
Problem

There are countless numbers of scientific studies published in countless scientific journals on subjects related to restorative dentistry.

Purpose

The purpose of this article is to review pertinent scientific studies published in 2017 on topics of interest to restorative dentists.

Methods and materials

The authors, considered to be experts in their disciplines searched the scientific literature in 7 different areas (prosthodontics, periodontics, dental materials, occlusion and temporomandibular disorders, sleep-disordered breathing, oral medicine and oral and maxillofacial surgery and dental caries). Pertinent articles were either identified and referenced or reviewed.

Results

A total of 437 articles in 7 disciplines were identified or reviewed.

Conclusions

An impressive amount of scientific literature related to restorative dentistry was published in 2017. The evidence presented in this article can assist dentists in the practice of contemporary evidence-based dentistry.



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The Essentials

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s):



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Table of Contents

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s):



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Editorial Board

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s):



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Changes in the flexural strength of translucent zirconia due to glazing and low-temperature degradation

Publication date: December 2018

Source: The Journal of Prosthetic Dentistry, Volume 120, Issue 6

Author(s): Min-Gyeong Nam, Mi-Gyoung Park

Abstract
Statement of problem

Surface glazing and low-temperature degradation (LTD) can affect the mechanical properties of zirconia, which is used to fabricate monolithic ceramic crowns.

Purpose

The purpose of this in vitro study was to assess the changes in flexural strength of monolithic ceramic crowns fabricated from translucent zirconia due to surface glazing and LTD.

Material and methods

Sixty plates of zirconia (25×4×1.2 mm) were milled and sintered. They were classified into 4 groups according to glazing and LTD (n=15): control, glazing, LTD, and LTD after glazing. A 3-point flexural test was performed with a universal testing machine. X-ray diffraction (XRD) was used to observe changes in the crystal structures of each group, and field emission scanning electron microscopy was used to observe the sizes of the crystal grains. Two-way analysis of variance was used to evaluate the results of the flexural strength tests, and the Tukey honestly significant difference test was performed for post hoc analysis (α=.05).

Results

The flexural strength showed significant differences due to glazing (P<.01). No significant differences were found due to LTD (P>.05). The crystal grain size increased with decreasing flexural strength of the specimens. XRD showed monoclinic phases in the groups subjected to LTD.

Conclusions

Glazing significantly reduced the flexural strength of translucent zirconia. LTD decreased the flexural strength of glazed translucent zirconia, but not to a significant extent.



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Validation of an Ultrasound Protocol to Measure Intervertebral Axial Twist during Functional Twisting Movements in Isolated Functional Spinal Units

Publication date: Available online 11 December 2018

Source: Ultrasound in Medicine & Biology

Author(s): Colin D. McKinnon, Jack P. Callaghan

Abstract

Ultrasound has potential for use in evaluation of bone and joint movement during axial twist of the lumbar spine both in vivo and in vitro. Such segmental rotations could then be measured under controlled external thoracic axial twist conditions and in response to mechanical loading. The purpose of this study was to measure vertebral segmental rotations in a porcine model of the human lumbar spine using an ultrasound imaging protocol and to validate use of this imaging technique with an optical motion capture system. In part 1, ultrasound transducer angle was confirmed to have no effect on sonogram point digitization. In part 2, 12 porcine functional spinal units were fixed to a mechanical testing system, and compression (15% of compressive tolerance), flexion–extension and axial twist (0°, 2°, 4° or 6°) were applied. Axial twist motion was tracked using an optical motion capture system and posterior surface ultrasound. Correlation between the two measurement systems was >0.903, and absolute system error was 0.01° across all flexion–extension postures. These findings indicate that ultrasound can be used to track axial twist motion in an in vitro spine motion segment and has the potential for use in vivo to evaluate absolute intervertebral axial twist motion.



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Does MR enterography offer added value after a recent CT in the evaluation of abdominal pain in Crohn's disease patients?

Publication date: Available online 10 December 2018

Source: Clinical Imaging

Author(s): Michael Spektor, Mahan Mahtur, Guido Santacana, Daniella Asch, Steffen Huber, Lawrence Staib, Gary Israel

Abstract
Purpose

To determine if there is added value in performing MR enterography shortly after a contrast-enhanced CT of the abdomen and pelvis in patients with Crohn's disease presenting with acute abdominal pain.

Materials and methods

A total of 45 consecutive patients who underwent MRE examination <7 days after a CT met our strict inclusion criteria. Independent and blinded review of both MRE and CT exams was performed by two abdominal radiologists.

Results

There were no significant differences in detection of various findings associated with Crohn's disease between modalities. These findings included abscess, fistula, bowel wall thickening, free fluid, stricture, and bowel obstruction. There was moderate interobserver agreement with CT (Kappa: 0.52, 95% CI: [0.4–0.6]) and fair with MRE (Kappa: 0.36, 95% CI:[0.3 = 0.5]).

Conclusion

The routine use of MRE after a diagnostic CT should be avoided, as it provides no additional valuable information, at the expense of extra patient risks, discomfort, and higher health care costs.



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Computed tomography imaging characteristics of primary atrial intimal sarcoma

Publication date: Available online 10 December 2018

Source: Clinical Imaging

Author(s): Mitchell Edquist, Christopher Lui, German Kilimnik, Hillel Karp

Abstract

We present a 36-year-old man who presented to our emergency department with acute onset shortness of breath and syncope. He was found to have a large left atrial mass on initial computed tomography (CT) which was confirmed by echocardiography. Tumor biopsy and attempted excision were performed, showing a primary cardiac spindle cell sarcoma that was unable to be resected, to which the patient eventually succumbed to. Spindle cell sarcomas of the heart are very rare primary cardiac tumors, with a variable, non-specific presentation. The most effective treatment is surgical resection, with chemotherapy and radiotherapy showing some benefit. Despite these treatments, the prognosis is poor. Given the uncommon nature of this tumor, the objective of this report is to demonstrate the clinical presentation and CT imaging characteristics of a case of primary cardiac spindle cell sarcoma, to raise awareness of this entity, and to increase the index of suspicion as a potential differential diagnosis to cardiac tumors seen on imaging.



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Siglec-8 in eosinophilic disorders: receptor expression and targeting using chimeric antibodies

Publication date: Available online 10 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Fanny Legrand, Yun Cao, Joshua Wechsler, Xiang Zhu, Nives Zimmermann, Shakuntala Rampertaap, Joseph Monsale, Kimberly Romito, Bradford A. Youngblood, Emily C. Brock, Michelle Makiya, Nenad Tomasevic, Christopher Bebbington, Irina Maric, Dean D. Metcalfe, Bruce S. Bochner, Amy D. Klion

Abstract
Background

Sialic acid–binding immunoglobulin-like lectin (Siglec)-8 is selectively expressed on eosinophils, mast cells and basophils, and, when engaged on eosinophils, can cause cell death.

Objective

To characterize surface and soluble Siglec-8 levels in normal (ND) and eosinophilic (EO) subjects and assess the efficacy of anti-Siglec-8 antibodies in inducing eosinophil cell death in vitro.

Methods

Eosinophil expression of Siglec-8 was assessed using flow cytometry and quantitative PCR. Serum soluble Siglec-8 levels were measured by ELISA. Induction of eosinophil death by IgG4 (c2E2 IgG4) and afucosylated IgG1 (c2E2 IgG1) anti-Siglec-8 antibodies was evaluated in vitro by flow cytometry and in vivo in humanized mice.

Results

Siglec-8 was consistently expressed on eosinophils from ND and EO and did not correlate with absolute eosinophil count (AEC) or disease activity. Soluble Siglec-8 levels were measurable in serum from most donors, unrelated to AEC or Siglec-8 surface expression. c2E2 IgG1 and c2E2 IgG4 were equally effective at inducing cell death (Annexin-V positivity) of purified eosinophils from ND and EO after overnight IL-5 priming. In contrast, killing of purified eosinophils without IL-5 was only seen in EO subjects, and NK-mediated eosinophil killing was seen only with c2E2 IgG1. Finally, treatment of humanized mice with anti-Siglec antibody led to robust depletion of IL-5-induced eosinophilia in vivo.

Conclusions

Siglec-8 is highly expressed on blood eosinophils from EO and ND and represents a potential therapeutic target for eosinophilic disorders. Enhanced killing of eosinophils in the presence of IL-5 may lead to increased efficacy in patients with IL-5-driven eosinophilia.

Graphical abstract

Graphical abstract for this article



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Integrating the PILP-mineralization process into a restorative dental treatment

Publication date: Available online 10 December 2018

Source: Dental Materials

Author(s): Margot Bacino, Vishavjeet Girn, Hamid Nurrohman, Kuniko Saeki, Sally J Marshall, Laurie Gower, Ella Saeed, Ray Stewart, Thuan Le, Grayson W Marshall, Stefan Habelitz

Abstract

The addition of charged polymers, like poly-aspartic acid (pAsp), to mineralizing solutions allows for transport of calcium and phosphate ions into the lumen of collagen fibrils and subsequent crystallization of oriented apatite crystals by the so-called Polymer-Induced Liquid Precursor (PILP) mineralization process, leading to the functional recovery of artificial dentin lesions by intrafibrillar mineralization of collagen.

Objective

To evaluate the feasibility of applying the PILP method as part of a restorative treatment and test for effectiveness to functionally remineralize artificial lesions in dentin.

Materials and Methods

Two methods of providing pAsp to standardized artificial lesions during a restorative procedure were applied: (A) pAsp was mixed into commercial RMGI (resin modified glass ionomer) cement formulations and (B) pAsp was added at high concentration (25 mg/ml) in solution to rehydrate lesions before restoring with a RMGI cement. All specimens were immersed in simulated body fluid for two weeks to allow for remineralization and then analyzed for dehydration shrinkage, integrity of cement-dentin interface, degree of mineralization, and changes in the nanomechanical profile (E-modulus) across the lesion.

Results

After the remineralization treatment, lesion shrinkage was significantly reduced for all treatment groups compared to demineralized samples. Pores developed in RMGI when pAsp was added. A thin layer at the dentin-cement interface, rich in polymer formed possibly from a reaction between pAsp and the RMGI. When analyzed by SEM under vacuum, most lesions delaminated from the cement interface. EDS-analysis showed some but not full recovery of calcium and phosphorous levels for treatment groups that involved pAsp. Nanoindentations placed across the interface indicated improvement for RMGI containing 40% pAsp, and were significantly elevated when lesions were rehydrated with pAsp before being restored with RMGI. In particular the most demineralized outer zone recovered substantially in the elastic modulus, suggesting that functional remineralization has been initiated by pAsp delivery upon rehydration of air-dried demineralized dentin. In contrast, the effectiveness of the RMGI on functional remineralization of dentin was minimal when pAsp was absent.

Significance

Incorporation of pAsp into restorative treatments using RMGIs promises to be a feasible way to induce the PILP-mineralization process in a clinical setting and to repair the structure and properties of dentin damaged by the caries process.



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Biomimetic regulation of dentine remineralization by amino acid in vitro

Publication date: Available online 10 December 2018

Source: Dental Materials

Author(s): Yuanmei Zhang, Zhejun Wang, Tao Jiang, Yining Wang

Abstract
Objective

The aim of this study was to evaluate the effect of conditioning solutions containing DL-aspartic amino (Asp) on dentine remineralization induced by bioactive glass 45S5 (BAG) in a simulated oral environment.

Methods

Sixty dentine discs from human third molars were used. Dentine specimens were treated with ethylene diamine tetraacetic acid (EDTA) to create a partially demineralization model and randomly divided to 4 groups: Artificial saliva (AS) group, Asp group (pretreated with Asp and remineralized with distilled water), BAG group (pretreated with distilled water and remineralized by BAG), Asp-BAG group (pretreated with Asp and remineralized by BAG).

Each samples were measured at various time points, and at the end of the experiment, 6% citric acid challenge were taken. The remineralization characteristics were analyzed by using the spectroscopic data from attenuated total reflectance spectroscopy (ATR-IR) and Raman spectroscopy. The micro-morphology and structure were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Dentine permeability was measured before and after each treatment to evaluate the resistance of remineralized layer to acid and simulated oral environment.

Results

Both BAG and Asp-BAG groups significantly reduced dentine permeability and formed enamel-like apatite layers on dentine surface. For the mineralization of BAG, Asp showed inhibition effect. The 7-day mineral matrix area ratio in BAG group (12.54 ± 2.29) was lower than the value in the Asp-BAG group (17.77 ± 2.27) (p < 0.05) and the Raman intensity (RI%) in Asp-BAG Group (1.49 ± 0.26) was also significantly higher than that of BAG group (1.34 ± 0.14) (p < 0.05). According to permeability test, the apatite layer in BAG group and Asp-BAG group effectively occluded the dentinal tubules (p < 0.05) and had certain acidic resistance (p > 0.05). Furthermore, adsorbed acidic amino acid on hydroxyapatite (HAP) altered the crystal to increase into a larger size in diameter during crystal growth.

Significance

The study demonstrated that a superior remineralization efficacy of BAG with Asp pretreatment on dentine.



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Performance of Diffusion Kurtosis Imaging Versus Diffusion Tensor Imaging in Discriminating Between Benign Tissue, Low and High Gleason Grade Prostate Cancer

Publication date: Available online 11 December 2018

Source: Academic Radiology

Author(s): Maria Giovanna Di Trani, Marco Nezzo, Alessandra S. Caporale, Riccardo De Feo, Roberto Miano, Alessandro Mauriello, Pierluigi Bove, Guglielmo Manenti, Silvia Capuani

Rationale and Objectives

To investigate the performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in discriminating benign tissue, low- and high-grade prostate adenocarcinoma (PCa).

Materials and Methods

Forty-eight patients with biopsy-proven PCa of different Gleason grade (GG), who provided written informed consent, were enrolled. All subjects underwent 3T DWI examinations by using b values 0, 500, 1000, 1500, 2000, and 2500 s/mm2 and six gradient directions. Mean diffusivity, fractional anisotropy (FA), apparent kurtosis (K), apparent kurtosis-derived diffusivity (D), and proxy fractional kurtosis anisotropy (KFA) maps were obtained. Regions of interest were selected in PCa, in the contralateral benign zone, and in the peritumoral area. Histogram analysis was performed by measuring mean, 10th, 25th, and 90th (p90) percentile of the whole-lesion volume. Kruskal–Wallis test with Bonferroni correction was used to assess significant differences between different regions of interest. The correlation between diffusion metrics and GG and between DKI and DTI parameters was evaluated with Pearson's test. ROC curve analysis was carried out to analyze the ability of histogram variables to differentiate low- and high-GG PCa.

Results

All metrics significantly discriminated PCa from benign and from peritumoral tissue (except for K, KFAp90, and FA). Kp90 showed the highest correlation with GG and the best diagnostic ability (area under the curve = 0.84) in discriminating low- from high-risk PCa.

Conclusion

Compared to DTI, DKI provides complementary and additional information about prostate cancer tissue, resulting more sensitive to PCa-derived modifications and more accurate in discriminating low- and high-risk PCa.



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Calibrated Breast Density Measurements

Publication date: Available online 10 December 2018

Source: Academic Radiology

Author(s): Erin E. Fowler, Autumn Smallwood, Nadia Khan, Cassandra Miltich, Jennifer Drukteinis, Thomas A. Sellers, John Heine

Rationale and Objectives

Mammographic density is an important risk factor for breast cancer, but translation to the clinic requires assurance that prior work based on mammography is applicable to current technologies. The purpose of this work is to evaluate whether a calibration methodology developed previously produces breast density metrics predictive of breast cancer risk when applied to a case–control study.

Materials and Methods

A matched case control study (n = 319 pairs) was used to evaluate two calibrated measures of breast density. Two-dimensional mammograms were acquired from six Hologic mammography units: three conventional Selenia two-dimensional full-field digital mammography systems and three Dimensions digital breast tomosynthesis systems. We evaluated the capability of two calibrated breast density measures to quantify breast cancer risk: the mean (PGm) and standard deviation (PGsd) of the calibrated pixels. Matching variables included age, hormone replacement therapy usage/duration, screening history, and mammography unit. Calibrated measures were compared to the percentage of breast density (PD) determined with the operator-assisted Cumulus method. Conditional logistic regression was used to generate odds ratios (ORs) from continuous and quartile (Q) models with 95% confidence intervals. The area under the receiver operating characteristic curve (Az) was also used as a comparison metric. Both univariate models and models adjusted for body mass index and ethnicity were evaluated.

Results

In adjusted models, both PGsd and PD were statistically significantly associated with breast cancer with similar Az of 0.61–0.62. The corresponding ORs and confidence intervals were also similar. For PGsd, the OR was 1.34 (1.09, 1.66) for the continuous measure and 1.83 (1.11, 3.02), 2.19 (1.28, 3.73), and 2.20 (1.26, 3.85) for Q2–Q4. For PD, the OR was 1.43 (1.16, 1.76) for the continuous measure and 0.84 (0.52, 1.38), 1.96 (1.19, 3.23), and 2.27 (1.29, 4.00) for Q2–Q4. The results for PGm were slightly attenuated and not statistically significant. The OR was 1.22 (0.99, 1.51) with Az = 0.60 for the continuous measure and 1.24 (0.78, 1.97), 0.98 (0.60, 1.61), and 1.26, (0.77, 2.07) for Q2–Q4 with Az = 0.60.

Conclusion

The calibrated PGsd measure provided significant associations with breast cancer comparable to those given by PD. The calibrated PGm performed slightly worse. These findings indicate that the calibration approach developed previously replicates under more general conditions.



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Influence of Inspiratory/Expiratory CT Registration on Quantitative Air Trapping

Publication date: Available online 10 December 2018

Source: Academic Radiology

Author(s): Oliver Weinheimer, Benjamin A. Hoff, Aleksa B. Fortuna, Antonio Fernández-Baldera, Philip Konietzke, Mark O. Wielpütz, Terry E. Robinson, Craig J. Galbán

Rationale and Objectives

The aim of this study was to assess variability in quantitative air trapping (QAT) measurements derived from spatially aligned expiration CT scans.

Materials and Methods

Sixty-four paired CT examinations, from 16 school-age cystic fibrosis subjects examined at four separate time intervals, were used in this study. For each pair, visually inspected lobe segmentation maps were generated and expiration CT data were registered to the inspiration CT frame. Measurements of QAT, the percentage of voxels on the expiration CT scan below a set threshold were calculated for each lobe and whole-lung from the registered expiration CT and compared to the true values from the unregistered data.

Results

A mathematical model, which simulates the effect of variable regions of lung deformation on QAT values calculated from aligned to those from unaligned data, showed the potential for large bias. Assessment of experimental QAT measurements using Bland-Altman plots corroborated the model simulations, demonstrating biases greater than 5% when QAT was approximately 40% of lung volume. These biases were removed when calculating QAT from aligned expiration CT data using the determinant of the Jacobian matrix. We found, by Dice coefficient analysis, good agreement between aligned expiration and inspiration segmentation maps for the whole-lung and all but one lobe (Dice coefficient > 0.9), with only the lingula generating a value below 0.9 (mean and standard deviation of 0.85 ± 0.06).

Conclusion

The subtle and predictable variability in corrected QAT observed in this study suggests that image registration is reliable in preserving the accuracy of the quantitative metrics.



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The strength of alpha and gamma oscillations predicts behavioral switch costs

Publication date: Available online 10 December 2018

Source: NeuroImage

Author(s): Amy L. Proskovec, Alex I. Wiesman, Tony W. Wilson

Abstract

Cognitive flexibility is often examined using task-switch paradigms, whereby individuals either switch between tasks or repeat the same task on successive trials. The behavioral costs of switching in terms of accuracy and reaction time are well-known, but the oscillatory dynamics underlying such costs are poorly understood. Herein, we examined 25 healthy adults who performed a task-switching paradigm during magnetoencephalography (MEG). All MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged separately per condition (i.e., switch, repeat) using a beamformer. To determine the impact of task switching on the neural dynamics, the resulting images were examined using paired-samples t-tests. Whole-brain correlations were also computed using the switch-related difference images (switch – repeat) and the switch-related behavioral data (i.e., switch costs). Our key results indicated stronger decreases in alpha and beta activity, and greater increases in gamma activity in nodes of the cingulo-opercular and fronto-parietal networks during switch relative to repeat trials. In addition, behavioral switch costs were positively correlated with switch-related differences in right frontal and inferior parietal alpha activity, and negatively correlated with switch effects in anterior cingulate and right temporoparietal gamma activity. In other words, participants who had a greater decrease in alpha or increase in gamma in these respective regions had smaller behavioral switch costs, which suggests that these oscillations are critical to supporting cognitive flexibility. In sum, we provide novel data linking switch effects and gamma oscillations, and employed a whole-brain approach to directly link switch-related oscillatory differences with switch-related performance differences.



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