Anti-Inflammatory Effects of Aster incisus through the Inhibition of NF-κB, MAPK, and Akt Pathways in LPS-Stimulated RAW 264.7 Macrophages

Aster incisus is a common flower found in almost all regions of South Korea. In the current study, we investigated the potential antioxidant and anti-inflammatory properties of the Aster incisus methanol extract in LPS-stimulated RAW 264.7 cells. We analyzed the phytochemicals contained in the extract by GC-MS. GC-MS results showed that the Aster incisus extract contains 9 known compounds. Later on, DPPH assay, WST-1 assay, nitric oxide (NO) assay, Western blot, and RT-PCR were conducted to investigate the anti-inflammatory effects of the extract. Our WST-1 assay results revealed that Aster incisus did not affect the viability of all tested cell lines up to a concentration of 200 μg/ml; therefore, lower concentrations (50 μg/ml and 150 μg/ml) were used for further assays. Aster incisus scavenged DPPH and inhibited the production of NO. Aster incisus also reduced significantly the production of inflammation-related enzymes (iNOS, Cox-2) and cytokines (TNFα, IL-1β, and IL-6) and the gene expression of the proinflammatory cytokines. Additionally, further Western blot results indicated that Aster incisus inhibited the expression of p-PI3K, p-IκBα, p-p65 NF-κB, p-ERK1/2, p-SAPK/JNK, and p-Akt. Our results demonstrated that Aster incisus suppressed the expression of the inflammation mediators through the regulation of NF-κB, MAPK, and Akt pathways.

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Der p 1‐specific regulatory T cell response during house dust mite allergen immunotherapy

Abstract

Background

Allergen‐specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen‐specific regulatory T (Treg) cells.

Methods

We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite‐specific immunotherapy. Peripheral blood mononuclear cells were studied before, after 10 weeks, 30 weeks and 3 years of AIT. Der p 1‐specific T regulatory cell responses was investigated by characterization of Der p 1‐MHC‐class II tetramer‐positive cells and correlated with nasal symptom score.

Results

Twelve of 25 AIT patients matched with their MHC‐class II expression to the Der p 1 peptide‐MHC‐class II tetramers. A significant increase in the numbers of Der p 1‐specific FOXP3⁺Helios⁺CD25⁺CD127^‐ Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1‐specific immunoglobulin‐like transcript 3 (ILT3)⁺CD25⁺ Treg cells decreased substantially from baseline after 3 years of AIT. ILT3⁺ Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1‐specific IL‐10 and IL‐22 responses have increased after 30 weeks, but only IL‐10⁺ Der p 1‐specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3⁺Helios⁺, IL‐10⁺ and decreased ILT3⁺ Treg cell responses correlated with improved allergic symptoms.

Conclusion

The results indicate that AIT involves upregulation of the activated allergen‐specific Treg cells and downregulation of dysfunctional allergen‐specific Treg cells subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.

This article is protected by copyright. All rights reserved.

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The efficiency of extended postoperative antibiotic prophylaxis in orthognathic surgery: a prospective, randomized, double-blind, placebo-controlled clinical trial

Postoperative antibiotics are commonly administered in orthognathic surgery, despite the fact that there is no consensus regarding their efficacy. The objective of this study was to investigate the effectiveness of postoperative antibiotics in orthognathic surgery by conducting a prospective, randomized, double-blind, placebo-controlled trial.Patients were randomly allocated into one of two study groups: the intervention group (treated with 1 gram of intravenous (IV) amoxicillin-clavulanate TID) or the placebo group (treated with 50 mL of IV 0.9% NaCl TID).

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Computer-assisted surgery for reconstruction of complex mandibular defects using osteomyocutaneous microvascular fibular free flaps: Use of a skin paddle-outlining guide for soft-tissue reconstruction. A technical report

We present our pre-operative virtual planning of complex mandibular reconstruction with a microvascular fibular composite free flap and its harvesting using our novel cutaneous positioning guide based on the perforator vessels for our soft tissue reconstructive surgery.

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A pilot study of modified resection for anterior floor of the mouth squamous cell carcinoma without infiltration of the mandible

To explore the application of modified resection compared with traditional segmental resection of the mandible for patients with anterior floor of the mouth and tongue squamous cell carcinoma (SCC) without infiltration of the mandible.

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

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

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

Certain patients with facial deformities require superior repositioning of the maxilla via Le Fort I osteotomy; however, the magnitude of superior repositioning of the maxilla is often less than expected. In this study, the correlation between the accuracy of superior repositioning of the maxilla and the anatomical form of the maxillary posterior region was examined. Seventy-five patients who underwent Le Fort I osteotomy without forward movement of the maxilla but with superior repositioning of the maxilla were included in this study.

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Horizontal alveolar transport distraction osteogenesis followed by implant placement

Alveolar transport distraction osteogenesis (ATDO) is an alternative treatment method to vertical alveolar distraction osteogenesis in cases of large bony defects, especially when the bone is limited in size. ATDO was performed in 10 patients with 12 defects. The mean age of the patients was 39.1years. The average bone length gain was 18.2mm. Implants were inserted following a 3-month consolidation period. Three patients needed additional bone grafting for horizontal widening. Final prosthetic rehabilitation was performed at least 3 months following implant insertion.

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Single-stage planning for total cure of grade III–V brain arteriovenous malformations by embolization alone or in combination with microsurgical resection

Abstract

Purpose

There are no established guidelines for treatment of Spetzler–Martin grade III–V brain arteriovenous malformations (bAVMs). The purpose of this study is to report our institutional experience in total obliteration/eradication of grade III–V bAVMs by single-stage planning of embolization combined with microsurgical resection when necessary.

Methods

All patients harboring Spetzler–Martin (S–M) grade III–V bAVMs treated with single-stage planning between January 2006 and January 2018 were retrospectively reviewed. This treatment paradigm is applicable only to surgically accessible bAVMs and does not include deep-seated bAVMs. Indications for treatment, clinical presentation, imaging characteristics, and treatment outcomes were analyzed. Outcomes were assessed based on modified Rankin Scale.

Results

A total of 31 patients were identified. Seventeen patients (54.8%) presented with hemorrhage, 10 (32.3%) with seizures, 3 (9.7%) with headaches, and 1 (3.2%) with progressive neurological deficit. Based on S–M grading system, 25 patients (80.6%) harbored grade III bAVM, 5 patients had grade IV bAVMs (16.1%), and 1 patient (3.2%) had a grade V bAVM. There were no treatment-related complications in 24/31 (77.4%) patients. Of the total of seven patients with complications, four patients had clinical deterioration. The long-term (> 6-month), non-disabling morbidity (mRS ≤ 2) rate was 6.5%. The long-term, disabling morbidity rate was 3.2% with a mortality of 3.2%. Complete angiographic obliteration was achieved in 30/31 (96.8%) patients.

Conclusion

Single-stage treatment strategy can be considered as an alternative to multistage embolization prior to surgery in grade III–V bAVMs. In this study, a high rate of total obliteration with relatively low rates of permanent morbidity and mortality was achieved.

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Submaximal primary angioplasty for symptomatic intracranial atherosclerosis: peri-procedural complications and long-term outcomes

Abstract

Purpose

The aim of our study is to report the peri-procedural complications and long-term stroke recurrent rate of symptomatic intracranial atherosclerosis (ICAS) patients who underwent submaximal primary angioplasty.

Methods

This is a retrospective analysis of consecutive patients in a single center who underwent submaximal primary angioplasty between January 1, 2012 and December 31, 2015. The peri-procedural complications and long-term outcomes are reported.

Results

Primary angioplasty was successfully performed in 129 patients (97.0%). The mean degree of pre-procedural stenosis was 81.9 ± 10.2%, and the degree of residual stenosis was 40.7 ± 19.1%. There were nine (6.8%) peri-procedural complications within 30 days, including seven ischemic strokes, one subarachnoid hemorrhage, and one asymptomatic intracerebral hemorrhage. None of them resulted in death. One-year follow-up was available in 122 patients (91.7%). Three more ischemic strokes (2.3%) which were in the territory of the treated artery occurred between 30 days and 1 year. The 1-year stroke and death rate was 9.0%, including peri-procedural stroke. Kaplan-Meier analysis showed a 3-year stroke-free survival of 87.2%.

Conclusion

Submaximal primary angioplasty can be performed with a low peri-procedural complication rate and relatively good clinical outcome at long-term follow-up for symptomatic ICAS patients.

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Impaired eating‐related quality of life in chronic rhinosinusitis

Background

Despite the tremendous burden of smell and taste dysfunction in patients with chronic rhinosinusitis (CRS), objective measures of smell and taste fail to fully account for eating‐related disruptions in CRS patient quality of life (QOL). In this study we sought to investigate the driving force behind impaired eating‐related QOL in CRS patients.

Methods

Adult CRS patients were prospectively enrolled and answered a series of surveys relating to smell, taste, overall sinus‐specific QOL, and depression. Patients with both smell‐related and taste‐related eating complaints were considered to have impaired eating‐related QOL. Clinical demographics, objective chemosensory scores, and endoscopy scores were collected.

Results

Seventy patients were enrolled and 23% showed impaired eating‐related QOL. In multivariable analyses, patients with aspirin‐exacerbated respiratory disease (AERD) showed 10.7 times higher odds of impaired eating‐related QOL (odds ratio [OR] 10.72; 95% confidence interval [CI], 1.09 to 105.09; p = 0.042); meanwhile, for every 1‐point increase in depression scores, the odds of impaired eating‐related QOL increased by 1.3 (OR 1.31; 95% CI, 1.10 to 1.57; p = 0.003). For every 1‐point decrease in orthonasal olfactory threshold, the odds of impaired eating‐related QOL increased by 1.9 times (OR 1.85; 95% CI, 1.14 to 3.00; p = 0.013). Symptom scores, polyp status, endoscopic scores, and other olfactory measures did not remain significant after adjusting for other variables in forward‐selection multivariable modeling.

Conclusion

Disruptions in eating‐related QOL cannot be fully explained by objective smell or taste testing alone. We identified AERD and depression as independent risk factors for greater odds of impaired eating‐related QOL in CRS. Improved orthonasal threshold scores were independently associated with better eating‐related QOL.

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Pathogenesis investigation of miR‐199‐5p in oral submucous fibrosis based on bioinformatics analysis

Abstract

Objectives

Fibrosis diseases are one of the leading causes of suffering and death. However, no systematic investigation has been carried out on fibrosis‐related genes.

Materials and Methods

By querying PubMed using keywords "fibrosis" and "gene" or "protein", we identified fibrosis‐related genes in the last decade. Bioinformatics analysis was performed by MAS 3.0 software. Key miRNA was selected to assesse its relationship with oral submucous fibrosis (OSF) and fibroblast functions.

Results

1310 genes related to fibrosis were identified. TGF‐β1, CTGF, MMP9, HSP47 and S1P were found to be associated with mainly fibrotic organs. 244 cellular components terms, 595 molecular function terms, 1816 cellular component terms, 136 KEGG pathway annotations were predicted. MiR‐199‐5p was selected as the key miRNA, which has higher level in OSF. Upregulated miR‐199‐5p was significantly related to OSF duration and OSF histological grade (P = 0.028 and 0.012, respectively). Overexpressive miR‐199‐5p reduced proliferation and induced apoptosis in buccal fibroblasts. Additionally, expression levels of collagen I (COL I) and III (COL III) were promoted by overexpressive miR‐199‐5p in buccal fibroblasts.

Conclusion

These results indicate that fibrosis‐related genes are related to a series of complex mechanisms. The characteristics of miR‐199‐5p may supply important clues for developing therapeutic strategy for OSF.

This article is protected by copyright. All rights reserved.

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Laundry detergents and detergent residue after rinse directly disrupt tight junction barrier integrity in human bronchial epithelial cells

Publication date: Available online 27 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Ming Wang, Ge Tan, Andrzej Eljaszewicz, Yifan Meng, Paulina Wawrzyniak, Swati Acharya, Can Altunbulakli, Patrick Westermann, Anita Dreher, Liying Yan, Chengshuo Wang, Mubeccel Akdis, Luo Zhang, Kari C. Nadeau, Cezmi A. Akdis

Abstract

Background

Defects in epithelial barrier have recently been associated with asthma and other allergies. The influence of laundry detergents on human bronchial epithelial cells (HBECs) and their barrier function remain unknown.

Objective

We investigated the effects of laundry detergents on cytotoxicity, barrier function, transcriptome and epigenome in HBECs.

Methods

Air-liquid interface cultures of primary HBECs from healthy control subjects, asthma and chronic obstructive pulmonary disease patients were exposed to laundry detergents and detergent residue after rinse. The cytotoxicity and epithelial barrier function were evaluated. RNA sequencing, assay for transposase accessible chromatin with high-throughput sequencing and DNA methylation arrays were used for checking transcriptome and epigenome.

Results

Laundry detergents and rinse residue showed dose dependent toxic effect to HBECs with irregular cell shape and leakage of lactate dehydrogenase after 24h exposure. A disrupted epithelial barrier function was found with decreased transepithelial electric resistance, increased paracellular flux and stratified tight junction immunostaining in HBECs exposed to laundry detergent at 1:25,000 dilutions or rinse residue at further 1:10 dilutions. RNA sequencing analysis showed that lipid metabolism, apoptosis progress and epithelial-derived alarmins related genes were up-regulated, while cell adhesion related genes were down-regulated by laundry detergent at 1:50,000 dilutions after 24h exposure without substantially affecting chromatin accessibility and DNA methylation.

Conclusion

Our data demonstrate that laundry detergents even at a very high dilution and rinse residue show significant cell toxic and directly disruptive effects on the tight junction barrier integrity of HBECs without affecting the epigenome and tight junction genes expression.

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Diffusion tensor imaging of the optic disc in idiopathic intracranial hypertension?

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Hierarchy of speech-driven spectrotemporal receptive fields in human auditory cortex

Publication date: Available online 28 November 2018

Source: NeuroImage

Author(s): Jonathan H. Venezia, Steven M. Thurman, Virginia M. Richards, Gregory Hickok

Abstract

Existing data indicate that cortical speech processing is hierarchically organized. Numerous studies have shown that early auditory areas encode fine acoustic details while later areas encode abstracted speech patterns. However, it remains unclear precisely what speech information is encoded across these hierarchical levels. Estimation of speech-driven spectrotemporal receptive fields (STRFs) provides a means to explore cortical speech processing in terms of acoustic or linguistic information associated with characteristic spectrotemporal patterns. Here, we estimate STRFs from cortical responses to continuous speech in fMRI. Using a novel approach based on filtering randomly-selected spectrotemporal modulations (STMs) from aurally-presented sentences, STRFs were estimated for a group of listeners and categorized using a data-driven clustering algorithm. 'Behavioral STRFs' highlighting STMs crucial for speech recognition were derived from intelligibility judgments. Clustering revealed that STRFs in the supratemporal plane represented a broad range of STMs, while STRFs in the lateral temporal lobe represented circumscribed STM patterns important to intelligibility. Detailed analysis recovered a bilateral organization with posterior-lateral regions preferentially processing STMs associated with phonological information and anterior-lateral regions preferentially processing STMs associated with word- and phrase-level information. Regions in lateral Heschl's gyrus preferentially processed STMs associated with vocalic information (pitch).

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Accuracy and reliability of [11C]PBR28 specific binding estimated without the use of a reference region

Publication date: Available online 27 November 2018

Source: NeuroImage

Author(s): Pontus Plaven-Sigray, Martin Schain, Francesca Zanderigo, Lars Farde, Christer Halldin, Anton Forsberg, Andrea Varrone, Aurelija Jucaite, Simon Cervenka, Per Stenkrona, Karin Collste, Mats Lekander, Eva Kosek, Jon Lampa, Caroline Olgart Höglund, Ilan Rabiner, Roger Gunn, Todd Ogden, Simon Cervenka

Abstract

[11C]PBR28 is a positron emission tomography radioligand used to estimate the expression of 18 kDa translocator protein (TSPO). TSPO is expressed on glial cells and can function as a marker for immune activation. Since TSPO is expressed throughout the brain, no true reference region exists. For this reason, an arterial input function is required for accurate quantification of [11C]PBR28 binding and the most common outcome measure is the total distribution volume (V_T). Notably, V_T reflects both specific binding and non-displaceable binding (V_ND). Therefore, estimates of specific binding, such as binding potentials (e.g., BP_ND) and specific distribution volume (V_S) should theoretically be more sensitive to underlying differences in TSPO expression. It is unknown, however, if unbiased and accurate estimates of these measures are obtainable for [11C]PBR28.

The Simultaneous Estimation (SIME) method uses time-activity-curves from multiple brain regions with the aim to obtain a brain-wide estimate of V_ND, which can subsequently be used to improve the estimation of BP_ND and V_S. In this study we evaluated the accuracy of SIME-derived V_ND, and the reliability of resulting estimates of specific binding for [11C]PBR28, using a combination of simulation experiments and in vivo studies in healthy humans.

The simulation experiments, based on data from 54 unique [11C]PBR28 examination, showed that V_ND values estimated using SIME were both precise and accurate. Data from a pharmacological competition challenge (n = 5) showed that SIME provided V_ND values that were on average 19% lower than those obtained using the Lassen plot, but similar to values obtained using the Likelihood-Estimation of Occupancy technique. Test-retest data (n = 11) showed that SIME-derived V_S values exhibited good reliability and precision, while larger variability was observed in SIME-derived BP_ND values.

The results support the use of SIME for quantifying specific binding of [11C]PBR28, and suggest that V_S can be used in preference to, or as a complement to the conventional outcome measure V_T. Additional studies in patient cohorts are warranted.

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Combining resting state functional MRI with intraoperative cortical stimulation to map the mentalizing network

Publication date: Available online 27 November 2018

Source: NeuroImage

Author(s): Yordanka Nikolova Yordanova, Jérôme Cochereau, Hugues Duffau, Guillaume Herbet

Abstract

Objective

To infer the face-based mentalizing network from resting-state functional MRI (rsfMRI) using a seed-based correlation analyses with regions of interest identified during intraoperative cortical electrostimulation.

Methods

We retrospectively included 23 patients in whom cortical electrostimulation induced transient face-based mentalizing impairment during 'awake' craniotomy for resection of a right-sided diffuse low-grade glioma. Positive stimulation sites were recorded and transferred to the patients' preoperative normalized MRI, and then used as seeds for subsequent seed-to-voxel functional connectivity analyses. The analyses, conducted with an uncorrected voxel-level p-value of 0.001 and a false-discovery-rate cluster-level p-value of 0.05, allowed identification of the cortical structures, functionally coupled with the mentalizing-related sites.

Results

Two clusters of responsive stimulations were identified intraoperatively – one in the right dorsolateral prefrontal cortex (dlPFC, n = 13) and the other in the right inferior frontal gyrus (IFG, n = 10). A whole group level analysis revealed that stimulation sites correlated mainly with voxels located in the pars triangularis of the IFG, the dorsolateral and dorsomedial prefrontal cortices, the temporo-parietal junction, the posterior superior temporal sulcus, and the posterior inferior temporal/fusiform gyrus. Other analyses, taking into consideration the location of the responsive sites (IFG versus dlPFC cluster), highlighted only minor differences between both groups.

Conclusions

The present study successfully demonstrated the involvement of a large-scale neural network in the face-based mentalizing that perfectly matches networks, classically identified using task-based fMRI paradigms. We thus validated the combination of rsfMRI and stimulation mapping as a powerful approach to identify functional networks in brain-damaged patients.

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Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence

Publication date: Available online 27 November 2018

Source: NeuroImage

Author(s): Irene Esteban-Cornejo, Jose Mora-Gonzalez, Cristina Cadenas-Sanchez, Oren Contreras-Rodriguez, Juan Verdejo-Roman, Pontus Henriksson, Jairo H. Migueles, Maria Rodriguez-Ayllon, Pablo Molina-García, Chao Suo, Charles H. Hillman, Arthur F. Kramer, Kirk I. Erickson, Andrés Catena, Antonio Verdejo-García, Francisco B. Ortega

Abstract

Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examine: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8–11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm²). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (β = 0.321 and β = 0.302, respectively; both P < 0.05), and in turn, cortical thickness was associated with higher intelligence (β = 0.198, P < 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p > 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% & 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.

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Previous chronic symptomatic and asymptomatic cerebral hemorrhage in patients with acute ischemic stroke

Abstract

Purpose

Identifying previous chronic cerebral hemorrhage (PCH), especially asymptomatic cases in patients with ischemic stroke, is essential for proper antithrombotic management. The study aimed to further clarify the prevalence of PCH and the associated factors in patients with acute ischemic stroke using multi-modal neuroimaging including susceptibility-weighted MR imaging (SWI).

Methods

This was a retrospective cross-sectional study of 382 patients with acute ischemic stroke. All patients underwent 3.0-T MRI for cranial SWI, 1.5-T or 3.0-T conventional cranial MRI, and cranial CT. Patients found with PCH were matched 1:4 with patients without PCH. Clinical manifestation, computed tomography, conventional cranial MRI, and cranial SWI were used to determine PCH. Clinical and neuroimaging findings between the patients with symptomatic vs. asymptomatic PCH were compared.

Results

Thirty-six patients (36/382, 9.4%) were determined to have had a PCH. Of these 36 patients, 17 (17/36, 47.2%, or 17/382, 4.5%) had asymptomatic PCH. Multivariable analysis showed that serum total cholesterol (OR = 0.510, 95%CI 0.312–0.832, P = 0.007), cerebral microbleeds (OR = 6.251, 95%CI 2.220–17.601, P = 0.001), and antithrombotic drugs history (OR = 3.213, 95%CI 1.018–10.145, P = 0.047) were independently associated with PCH. Asymptomatic PCH had similar clinical and neuroimaging characteristics with symptomatic PCH.

Conclusion

PCH is not uncommon in acute ischemic stroke patients. Total serum cholesterol, cerebral microbleeds on SWI, and history of antithrombotic drugs were independently associated with PCH in patients with acute ischemic stroke. Asymptomatic PCH, which is easier to be missed and has similar characteristics with symptomatic PCH, should draw much attention.

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Radiomics for Classification of Lung Cancer Histological Subtypes Based on Nonenhanced Computed Tomography

Publication date: Available online 28 November 2018

Source: Academic Radiology

Author(s): Linning E, Lin Lu, Li Li, Hao Yang, Lawrence H. Schwartz, Binsheng Zhao

Objectives

To evaluate the performance of using radiomics method to classify lung cancer histological subtypes based on nonenhanced computed tomography images.

Materials and Methods

278 patients with pathologically confirmed lung cancer were collected, including 181 nonsmall cell lung cancer (NSCLC) and 97 small cell lung cancers (SCLC) patients. Among the NSCLC patients, 88 patients were adenocarcinomas (AD) and 93 patients were squamous cell carcinomas (SCC). In total, 1695 quantitative radiomic features (QRF) were calculated from the primary lung cancer tumor in each patient. To build radiomic classification model based on the extracted QRFs, several machine-learning algorithms were applied sequentially. First, unsupervised hierarchical clustering was used to exclude highly correlated QRFs; second, the minimum Redundancy Maximum Relevance feature selection algorithm was employed to select informative and nonredundant QRFs; finally, the Incremental Forward Search and Support Vector Machine classification algorithms were used to combine the selected QRFs and build the model. In our work, to study the phenotypic differences among lung cancer histological subtypes, four classification models were built. They were models of SCLC vs NSCLC, SCLC vs AD, SCLC vs SCC, and AD vs SCC. The performance of the classification models was evaluated by the area under the receiver operating characteristic curve (AUC) estimated by three-fold cross-validation.

Results

The AUC (95% confidence interval) for the model of SCLC vs NSCLC was 0.741(0.678, 0.795). For the models of SCLC vs AD and SCLC vs SCC, the AUCs were 0.822(0.755, 0.875) and 0.665(0.583, 0.738), respectively. The AUC for the model of AD vs SCC was 0.655(0.570, 0.731). Several QRFs ("Law_15," "LoG_Uniformity," "GLCM_Contrast," and "Compactness Factor") that characterize tumor heterogeneity and shape were selected as the significant features to build the models.

Conclusion

Our results show that phenotypic differences exist among different lung cancer histological subtypes on nonenhanced computed tomography image.

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Computer-assisted surgery for reconstruction of complex mandibular defects using osteomyocutaneous microvascular fibular free flaps: Use of a skin paddle-outlining guide for soft-tissue reconstruction. A technical report

Publication date: Available online 28 November 2018

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Salvatore Battaglia, Francesco Ricotta, Vincenzo Maiolo, Gabriella Savastio, Federico Contedini, Riccardo Cipriani, Barbara Bortolani, Laura Cercenelli, Emanuela Marcelli, Claudio Marchetti, Achille Tarsitano

Abstract

Introduction

We present our pre-operative virtual planning of complex mandibular reconstruction with a microvascular fibular composite free flap and its harvesting using our novel cutaneous positioning guide based on the perforator vessels for our soft tissue reconstructive surgery.

Technical Report

We applied our protocol to 42 consecutive patients needing mandibular composite reconstruction. All patients were preoperatively studied with a CTA scan to evaluate the fibular pattern of vascularization and the perforator vessels three-dimensional path and position. Computer assisted surgery (CAS) was performed: a skin paddle outlining guide (SPOG) was designed to reproduce the shape and area of the planned soft tissue resection. CTA measurements and in vivo findings were compared. After performing the CTA, we classified the viable perforators in High Perforators, Medium Perforators and Low Perforators. The average diameter of the perforator vessels was 3 mm. The average difference between the measurements performed on the CTA and the intra-operative measures was 1,4 mm. The SPOG was based on calf proximal and distal diameters. The anatomical fitting of the guide was obtained thanks to two customized flanges that embrace circumferentially the proximal and distal portions of the leg. The SPOG encompassed appropriate skin/leg regions, allowing the surgeon to localise the required perforator vessel.

Conclusions

CTA protocol appears to be a valuable approach to asses and virtually simulate composite mandibular reconstructions. The SPOG seems to be a valuable tool to reproduce intra-operatively the planned soft tissue area to be reconstructed.

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The efficiency of extended postoperative antibiotic prophylaxis in orthognathic surgery: a prospective, randomized, double-blind, placebo-controlled clinical trial

Publication date: Available online 28 November 2018

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Yasmine Ghantous, Sharif Araidy, Victoria Yaffe, Roman Mirochnik, Murad Abdol El-raziq, Imad Abu El-naaj

Abstract

Postoperative antibiotics are commonly administered in orthognathic surgery, despite the fact that there is no consensus regarding their efficacy. The objective of this study was to investigate the effectiveness of postoperative antibiotics in orthognathic surgery by conducting a prospective, randomized, double-blind, placebo-controlled trial.

Patients were randomly allocated into one of two study groups: the intervention group (treated with 1 gram of intravenous (IV) amoxicillin-clavulanate TID) or the placebo group (treated with 50 mL of IV 0.9% NaCl TID). The infection rate was assessed using clinical and laboratory parameters.

The intervention group included 38 patients, with 40 patients in the placebo group. Baseline and surgical characteristics were comparable between both groups. Mean postoperative C-reactive protein (CRP) and temperature were similar for both groups. Serous discharge was observed in two patients (both in the placebo group), and one of them required surgical intervention. Overall, infection rate was similar in both groups (p-value > 0.1).

To conclude, administration of postoperative antibiotics in healthy, young patients undergoing orthognathic surgery did not show a significant advantage in reducing surgical infection rate.

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A pilot study of modified resection for anterior floor of the mouth squamous cell carcinoma without infiltration of the mandible

Publication date: Available online 28 November 2018

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Zhien Feng, Chong Wang, Bo Li, Kyojin Kim, Jinzhong Li, Minghui Mao, Lizheng Qin, Hua Li, Zhengxue Han

Abstract

Objective

To explore the application of modified resection compared with traditional segmental resection of the mandible for patients with anterior floor of the mouth and tongue squamous cell carcinoma (SCC) without infiltration of the mandible.

Subjects

and Methods: This is a retrospective study including 36 eligible patients with anterior floor of the mouth SCC(9 patients received modified mandibulectomy, and 27 patients received segmental mandibulectomy).

Results

No patients in the modified mandibulectomy group developed recurrence in the floor of the mouth, and all of the patients survived. Only one patient developed osteoradionecrosis. When the modified mandibulectomy group was compared with the segmental mandibulectomy group, the former exhibited a lower recurrence rate in the floor of the mouth (0.0% vs. 14.8%), less blood loss (516.7 ± 70.7 ml vs. 533.3 ± 93.0 ml), shorter durations of gastric tube placement (11.4 ± 4.5 days vs. 20.7 ± 11.9 days) and tracheostomy (6.9 ± 0.6 days vs. 8.5 ± 1.6 days), a lower postoperative infection rate (11.1% vs. 18.5%), and a shorter postoperative hospital stay (13.7 ± 3.8 days vs. 15.9 ± 5.1 days).

Conclusion

This modified mandibulectomy method is safe and feasible and is recommended for further prospective study in a clinical setting.

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Contents

Publication date: January–February 2019

Source: Clinical Imaging, Volume 53

Author(s):

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Efficacy and safety of partial splenic embolization for hypersplenism in pre- and post-liver transplant patients: A 16-year comparative analysis

Publication date: Available online 27 November 2018

Source: Clinical Imaging

Author(s): Byron DuBois, David Mobley, Jeffrey Chick, Ravi Srinivasa, Chad Wilcox, Joshua Weintraub

Abstract

Purpose

To report the effect of partial splenic embolization (PSE) on hematological indices and the procedure's safety in pre- and post-liver transplant (LT) patients.

Materials and methods

A single-center retrospective study evaluating all patients who underwent PSE over a 16-year period was performed. Inclusion criteria were splenomegaly confirmed by imaging and at least one of the following cytopenias: hemoglobin ≤10 g/dL, WBC count ≤1500 μL⁻¹, or platelet count ≤100,000 μL⁻¹. 38 of 102 patients (37%) met criteria (24 pre- and 14 post-LT) for a total of 40 PSEs.

Results

No effect was seen on median hemoglobin beyond 2 weeks post-PSE. There was a significant and sustained increase in median WBC counts (from 3400 μL⁻¹ to 5400 μL⁻¹ at 2 years) and platelet count (from 65,000 μL⁻¹ to 117,000 μL⁻¹ at 3.5 years). In 6 out of 40 PSEs (15%) a major complication occurred which included pleural effusion, ascites, spontaneous bacterial peritonitis, pneumonia, and inferior vena cava thrombus. Similar efficacy was observed in pre- and post-LT cohorts, with a trend toward higher complication rate in pre-LT patients.

Conclusions

PSE is efficacious in increasing WBC out to 2 years and platelet counts out to 3.5 years in patients with hypersplenism. Efficacy and safety appeared independent of pre- or post-LT status. The intervention is associated with major complications and special care should be taken when selecting patients for PSE.

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Optimal sandblasting conditions for conventional-type yttria-stabilized tetragonal zirconia polycrystals

Publication date: Available online 28 November 2018

Source: Dental Materials

Author(s): Masahiro Okada, Hiroaki Taketa, Yasuhiro Torii, Masao Irie, Takuya Matsumoto

Abstract

Objective

To assess the influence of sandblasting conditions applied to conventional-type yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) on surface roughness, phase transformation, and biaxial flexural strength.

Methods

Commercially available Y-TZP (Lava Frame, 3M Dental Products) disks were used after sintering (specimen dimensions: 14 mm in diameter and 1.2 mm in thickness). The surfaces of specimens were ground, and then sandblast treatments were conducted at different pressures (0.20, 0.25, 0.30, 0.35 and 0.40 MPa) and distances (1, 5, 10 and 20 mm) with 50 μm alumina particles. Surface roughness measurements were performed and scanning electron microscopy (SEM) images were taken for surface characterizations. Phase transformation of Y-TZP was identified by X-ray diffraction (XRD). Biaxial flexural strength was measured using the piston-on-three-ball test.

Results

The surface roughness increased significantly by increasing the sandblasting pressure, and microcracks were observed at high sandblasting pressure at 0.40 MPa. The shortest sandblasting distance (1 mm) was not effective to increase the surface roughness compared with other sandblasting distances. A tetragonal to monoclinic phase transformation was observed after grinding. The degree of the phase transformation tended to increase with sandblasting pressure, and significant effect was independent of the sandblasting distance. The biaxial flexural test showed improved mechanical strengths for the samples after sandblasting at 0.20–0.35 MPa, with the maximum strength at 0.25 MPa. Sandblasting at 0.40 MPa decreased the strength as compared with 0.25 MPa.

Significance

The surface roughness increased with increasing the sandblasting pressure, whereas there was an optimal sandblasting pressure range to increase biaxial flexural strength of Y-TZP.

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Impaired angiogenic differentiation of dental pulp stem cells during exposure to the resinous monomer triethylene glycol dimethacrylate

Publication date: Available online 28 November 2018

Source: Dental Materials

Author(s): Peter Schertl, Joachim Volk, Renke Perduns, Knut Adam, Gabriele Leyhausen, Athina Bakopoulou, Werner Geurtsen

Abstract

Objective

Dental pulp stem cells (DPSCs) can differentiate into tissue specific lineages to support dental pulp regeneration after injuries. Triethylene glycol dimethacrylate (TEGDMA) is a widely used co-monomer in restorative dentistry with adverse effects on cellular metabolism. Aim of this study was to analyze the impact of TEGDMA on the angiogenic differentiation potential of DPSCs.

Methods

DPSCs were characterized by flow cytometry. Short-term (max. 72 h) cytotoxicity of TEGDMA was assessed by MTT assay. To evaluate TEGDMA effects on angiogenic differentiation, DPSCs were cultivated in angiogenic differentiation medium (ADM) in the presence or absence of short-term non-toxic TEGDMA concentrations (0.1 mM and 0.25 mM). Subsequently, angiogenic differentiation was analyzed by qRT-PCR analysis of mRNA markers and in vitro spheroid sprouting assays.

Results

DPSCs treated with 0.25 mM TEGDMA revealed downregulation of angiogenesis-related marker genes PECAM1 (max. 3.8-fold), VEGF-A (max. 2.4-fold) and FLT1 (max. 2.9-fold) compared to respective untreated control. In addition, a reduction of the sprouting potential of DPSCs cultured in the presence of 0.25 mM TEGDMA was detectable. Larger spheroidal structures were detectable in the untreated control in comparison to cells treated with 0.25 mM TEGDMA. In contrast, TEGDMA at 0.1 mM was not affecting angiogenic potential in the investigated time period (up to 28 days).

Significance

The results of the present study show that TEGDMA concentration dependently impair the angiogenic differentiation potential of DPSCs and may affect wound healing and the formation of granulation tissue.

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Upregulation of Cardiac IL-10 and Downregulation of IFN-γ in Balb/c IL-4−/− in Acute Chagasic Myocarditis due to Colombian Strain of Trypanosoma cruzi

Inflammatory response in Chagas disease is related to parasite and host factors. However, immune system regulation has not been fully elucidated. Thus, this study is aimed at evaluating IL-4 influence on acute phase of Trypanosoma cruzi experimental infection through dosage of cytokine levels in cardiac homogenate of infected Balb/c WT and Balb/c IL-4−/− as well as its histopathological repercussions. For such purpose, mice were divided into two groups: an infected group with 100 forms of the Colombian strain and an uninfected group. After 21 days of infection, animals were euthanized and the blood, spleen, and heart were collected. The spleen was used to culture splenic cells in 48 h. Subsequently, cytokines TNF-α, IL-12p70, IL-10, IFN-γ, and IL-17 were measured in the blood, culture supernatant, and heart apex by ELISA. The base of the heart was used for histopathological analysis. From these analysis, infected Balb/c IL-4−/− mice showed milder inflammatory infiltrate compared to Balb/c WT, but without changes in nest density and collagen deposition. IL-4 absence culminated in lower cardiac tissue IFN-γ production, although it did not affect TNF-α expression in situ. It also decreased TNF-α systemic production and increased IL-10, both systemically and in situ. In addition, IL-4 absence did not influence IL-17 expression. Splenocytes of IL-4-deficient mice produced higher amounts of IFN-γ, TNF-α, and IL-17 and lower amounts of IL-10. Thus, IL-4 absence in acute phase of experimental infection with T. cruzi Colombian strain reduces myocarditis due to lower IFN-γ production and greater IL-10 production in situ and this pattern is not influenced by splenocyte general repertoire.

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