OtoRhinoLaryngology News: 03/21/18

Τετάρτη 21 Μαρτίου 2018

Development of a Test Battery for Evaluating Speech Perception in Complex Listening Environments: Effects of Sensorineural Hearing Loss

Objective: To evaluate the speech-in-noise performance of listeners with different levels of hearing loss in a variety of complex listening environments. Design: The quick speech-in-noise (QuickSIN)-based test battery was used to measure the speech recognition performance of listeners with different levels of hearing loss. Subjective estimates of speech reception thresholds (SRTs) corresponding to 100% and 0% speech intelligibility, respectively, were obtained using a method of adjustment before objective measurement of the actual SRT corresponding to 50% speech intelligibility in every listening condition. Results: Of the seven alternative listening conditions, two conditions, one involving time-compressed, reverberant speech (TC+Rev), and the other (N0Sπ) having in-phase noise masker (N0) and out-of-phase target (Sπ), were found to be substantially more sensitive to the effect of hearing loss than the standard QuickSIN test. The performance in these two conditions also correlated with self-reported difficulties in attention/concentration during speech communication and in localizing the sound source, respectively. Hearing thresholds could account for about 50% or less variance in SRTs in any listening condition. Subjectively estimated SRTs (SRTs corresponding to 0% and 100% speech intelligibility) were highly correlated with the objective SRT measurements (SRT corresponding to 50% speech intelligibility). Conclusions: A test battery that includes the TC+Rev and the N0Sπ conditions would be useful in identifying individuals with hearing loss with speech-in-noise deficits in everyday communication. ACKNOWLEDGMENTS: This research was funded by the U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) through a Health Promotion and Preventive Initiative (HPPI) program grant. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government. The identification of specific products, scientific instrumentation, or organizations is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, DoD, or any component agency. The authors have no conflicts of interest to disclose. Address for correspondence: Sandeep A. Phatak, Walter Reed National Military Medical Center, Building 19, Room 5504, 8901 Rockville Pike, Bethesda, MD 20889, USA. E-mail: s.a.phatak@gmail.com Received July 25, 2017; accepted January 23, 2018. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Growth hormone promotes neurite growth of spiral ganglion neurons

Intact spiral ganglion neurons are a specific requirement for hearing rehabilitation in deaf patients by cochlear implantation. Neurotrophic growth factors have been proposed as effective tools to protect and regenerate spiral ganglion neurons that are degenerated in the majority of patients suffering from hearing loss. Here, we show that growth hormone (GH), a pleiotropic growth factor whose neurotrophic role in the inner ear is still unclear, significantly increases neurite extension, as well as neuronal branching, in spiral ganglion cell cultures derived from early postnatal rats. Our data suggest that GH can act as a potent neurotrophic factor for inner ear neurons, which specifically promotes neurite growth. These effects might be elicited in a direct way or, alternatively, by induction of other growth factors that account for the observed neurotrophic effects. Thus, we conlude that GH might represent a novel candidate for the treatment of neurodegeneration in the hearing-impaired inner ear that has the potential to ultimately improve the performance and outcome of modern auditory implants. Correspondence to Marc Diensthuber, MD, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany Tel: +49 696 301 5163; fax: +49 696 301 5435; e-mail: marc.diensthuber@kgu.de Received January 12, 2018 Accepted February 24, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Generation of human vascularized brain organoids

The aim of this study was to vascularize brain organoids with a patient's own endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis patient were grown into whole-brain organoids. Simultaneously, iPSCs from the same patient were differentiated into ECs. On day 34, the organoid was re-embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro for 3–5 weeks or transplanted into immunodeficient mice on day 54, and animals were perfused on day 68. Coating of brain organoids on day 34 with ECs led to robust vascularization of the organoid after 3–5 weeks in vitro and 2 weeks in vivo. Human CD31-positive blood vessels were found inside and in-between rosettes within the center of the organoid after transplantation. Vascularization of brain organoids with a patient's own iPSC-derived ECs is technically feasible. Correspondence to Ben Waldau, MD, Department of Neurological Surgery, UC Davis Medical Center, 4680 Y Street, ACC 3740, Sacramento, CA 95817, USA Tel: +1 916 734 6510, fax: +1 916 703 5368; e-mail: bwaldau@ucdavis.edu Received February 16, 2018 Accepted February 26, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Endoscopic Treatment of Duodenal Web in Association with Annular Pancreas in an Infant

No abstract available

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Prevalence of Suspected Nonalcoholic Fatty Liver Disease In Lean Adolescents In The United States

Objectives: Nonalcoholic fatty liver disease (NAFLD) can develop in lean subjects referred to as lean NAFLD. We aim to evaluate the prevalence and risk factors of NAFLD in lean adolescents in the United States (US). Methods: Cross sectional data from 1482 lean subjects (body mass index 25.8 U/L for boys and > 22.1 U/L for girls; hypertriglyceridemia as triglycerides ≥ 150 mg/dL; low HDL as HDL

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Clinical factors affecting salivary transferrin level, a marker of blood contamination in salivary analysis

Abstract

Background

Diagnostic value of whole saliva may be compromised when blood contamination is present in saliva samples. Measuring transferrin level in saliva samples has been used for detecting the level of blood contamination in saliva. The aim of this study was to investigate the validity of transferrin as a proper biomarker for blood contamination in whole saliva.

Methods

Thirty younger (mean age: 25.9 ± 2.1 years) and twenty older (mean age: 65.1 ± 9.0 years) females were included. The index reflecting overall gingival inflammation (total gingival index), salivary flow rate, and salivary concentration and secretion rate of transferrin of each subject were analyzed.

Results

Salivary transferrin concentrations and secretion rates were higher in the younger females than in the older ones despite a lower total gingival index in the younger females. The total gingival index showed no significant correlations with the concentration or secretion rate of transferrin in either unstimulated or stimulated whole saliva of younger and older subjects. The salivary concentration of transferrin showed negative correlations with the flow rate of saliva in both the younger and older groups. There were significant positive correlations between the salivary concentrations and secretion rates of transferrin in both the younger and older groups.

Conclusions

Salivary transferrin levels could be affected by other factors as well as the level of blood contamination. The influences of age, gonadal hormones, salivary flow rate, and chewing performance need to be considered when using the salivary level of transferrin as a blood contamination marker.

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Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup

Abstract

Purpose

The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [¹⁸F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup.

Methods

Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level.

Results

Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1–42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10⁻³ mm²/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = −0.31 ± 0.27, p < 0.05).

Conclusion

Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

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Micro-computed tomography-based anatomical study of the branch canals in mandibular anterior teeth in a Chinese population

Abstract

Objectives

To analyze the incidence and distribution of branch canals in mandibular anterior teeth.

Materials and methods

Three hundred mandibular anterior teeth, comprising 100 central incisors, 100 lateral incisors, and 100 canines, were scanned using a micro-computed tomography (micro-CT) system. Three-dimensional (3-D) visualization reconstruction of the root canal system and its branch canals was performed on each specimen. Data regarding the number of branch canals, the distance from the anatomical apex to the branch canal, and the orientation of each branch orifice were collected and analyzed.

Results

One hundred and fifty-three primary branch canals and 35 secondary branch canals were detected in the specimens overall. The incidence of branch canals in mandibular anterior teeth was 34%, with the highest incidence (50%) exhibited in mandibular canines, followed by lateral incisors (29%). Of the 153 primary branch canals found in the mandibular anterior tooth samples investigated, 82.35% appeared within 3 mm of the apical region, while 71.90% were labial and lingual canals.

Conclusions

There was regularity in the distribution and orientation of branch canals in mandibular anterior teeth.

Clinical relevance

This knowledge may be employed as a guide in clinical endodontic therapy.

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Fatty acid receptor GPR120: a novel marker for human melanoma

The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of G-protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long-chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma metastasis (n=43) were immunohistochemically stained against GPR120. The staining was evaluated by three trained dermatopathologists and independently scored. Compared with nevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120 expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0–10], whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS score: 7, range: 0–12) and in melanoma metastasis 27 out of 43 were highly GPR120-positive (median IRS score: 9, range: 0–12). GPR120 expression and tumor thickness (mm) show a statistically significant correlation in primary melanoma (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis and in sebaceous and sweat glands, which is yet not described. This study identified GPR120 as a novel marker for melanoma, indicating that melanoma cells are sensitive to free fatty acids. It is tempting to speculate that pharmacologically interfering with GPR120 signaling might improve melanoma therapy. Correspondence to Dr Johannes Kleemann, Department of Dermatology, Venereology and Allergy, University Hospital Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany Tel: +49 696 301 5343; fax: +49 696 301 6466; e-mail: johannes.kleemann@kgu.de Received October 23, 2017 Accepted February 13, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Telomerase reverse transcriptase promoter mutations and solar elastosis in cutaneous melanoma

The aims of this study were to assess the prognostic potential of solar elastosis grading and telomerase reverse transcriptase (TERT) promoter mutations (TERTpmut) in melanoma and to evaluate whether an association between solar elastosis and TERTpmut exists. Solar elastosis in the dermis was evaluated in hematoxylin and eosin-stained whole slides from 486 malignant melanomas. Pyrosequencing was used to detect TERTpmut in 189 samples. There was no association between solar elastosis and TERTpmut (P=0.3). Severe elastosis was associated with older age (P

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Incidence and management of arterial injuries during pancreatectomy

Abstract

Purpose

The incidence of intraoperative arterial injury during pancreatectomy is not well described. This study aims to evaluate the incidence, management, and outcome of arterial injuries during pancreatectomy.

Methods

This is a retrospective study of 1535 consecutive patients undergoing pancreatectomy between 2006 and 2016 at Oslo University Hospital. The type of arterial injury and potential contributing factors were analyzed. Short-term outcomes were compared between patients with arterial injury and patients undergoing a planned arterial resection due to tumor involvement.

Results

Arterial injury was diagnosed in 14 patients (incidence 0.91%), while planned arterial resection was performed in 22 patients. The injuries were located in the superior mesenteric artery (n = 5), right hepatic artery (n = 5), common hepatic artery (n = 2), left hepatic artery (n = 1), and celiac trunk (n = 2). The artery was reconstructed in all except one patient. In 11 patients with injury, peripancreatic inflammation, aberrant arterial anatomy, close relationship between tumor and injured artery, or a combination of the three were found. Median estimated blood loss was 1100 ml in both groups. Rate of severe complications (≥ Clavien grade IIIa), comprehensive complication index, and 90-day mortality for patients with intraoperative arterial injury vs planned arterial resection were 43 vs 45% (p = 0.879), median 35.9 vs 21.8 (p = 0.287), and 14.3 vs 4.5% (p = 0.551), respectively.

Conclusion

Arterial injury during pancreatectomy is an infrequent and manageable complication. Early recognition and primary repair in order to restore arterial liver perfusion may improve outcome. However, the morbidity is high and comparable to patients undergoing a planned arterial resection.

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Evaluation of condyle position in patients with Angle Class I, II, and III malocclusion using cone-beam computed tomography panoramic reconstructions

Abstract

Objectives

This study was performed to compare the positions of the right and left condyles between male and female patients with different Angle malocclusions using cone-beam computed tomography (CBCT) panoramic reconstructions.

Methods

The CBCT images of 60 patients (age of 18–37 years) were retrospectively evaluated. The patients were divided according to their Angle malocclusion classifications (Angle Classes I, II, and III). The condyle-to-eminence, condyle-to-fossa, and condyle-to-meatus distances were measured digitally using i-CAT software.

Results

The left and right condyle-to-fossa distances were the most variable parameters among the Angle classes. The right condyle-to-eminence and right condyle-to-fossa distances were significantly different among the classes. Male patients seemed to have a greater condyle-to-fossa distance on the right side in both the Class I and III groups. The mean distance from the condyle to eminence, condyle to fossa, and condyle to meatus on the right side was the greatest in the Angle Class II group.

Conclusions

In all three types of malocclusion (Angle Classes I, II, and III), the condyles on both the right and left sides were not exactly symmetric or centrally located within the glenoid fossa. This work emphasizes the differences in the condyle position between male and female patients. Furthermore, the symmetry and centricity of the condyles are not dependent on the patient's sex or type of malocclusion.

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Treatment, outcomes, and demographics in sinonasal sarcoma: a systematic review of the literature

Abstract

Background

Sarcomas comprise a diverse group of soft tissue mesenchymal malignancies. The sinuses and nasal region are a relatively rare site of sarcomas.

Methods

Retrospective review of the literature on sinonasal sarcomas from 1987-2017. Data were analyzed for demographics, treatment type, stage, and histopathologic type. Kaplan-Meier analysis was used to assess and compare survival.

Results

A total of 198 cases of sinonasal sarcoma were identified and analyzed. The median age at diagnosis was 39 years. Overall 5-, 10-, and 20-year survival was 61.3%, 58.9%, and 49.1%, respectively, and disease-free 5-, 10-, and 20-year survival was 53.2%, 49.1%, and 38.3%, respectively. Lymph node metastasis was present at diagnosis in 3.0% of cases, and distant metastasis was present in 3.5% of cases. On univariate analysis T stage, overall stage, treatment type, histopathologic subtype, and presence of distant metastasis significantly affected survival. On multivariate analysis overall stage alone significantly predicted overall survival. Open vs. endoscopic surgery, total radiation dose, and presence of neck metastasis did not significantly affect survival. Combined modality treatment was associated with higher survival rates than single modality therapy.

Conclusions

Sinonasal sarcoma is a relatively rare malignancy. Lower T and overall stage, lack of distant metastasis, and multimodality therapy were associated with improved survival. Certain histopathologic subtypes were associated with poorer survival.

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Facial soft tissue changes after nonsurgical rapid maxillary expansion: a systematic review and meta-analysis

Abstract

Background

The present systematic review and meta-analysis aimed to test the hypothesis that no facial soft tissue changes occur after nonsurgical rapid maxillary expansion (RME), in order to provide a reference for orthodontists.

Methods

PubMed, EMBASE, Cochrane Library, OVID, MEDLINE, CINAHL, Scopus, and ScienceDirect databases were electronically and manually searched up to December 2017, and randomized controlled, clinical controlled trials, cohort studies and retrospective studies where soft tissue changes were measured before and after nonsurgical RME were identified. Study appraisal and synthesis were performed by two reviewers who completed the study selection and quality assessment procedures independently and in duplicate. Data from the involved studies were pooled using Revman 5.3.

Results

A total of 1762 articles were identified after the removal of duplicates. After selection and quality assessment, 15 studies met the inclusion criteria for the systematic review, and 13 articles were ultimately included in the meta-analysis. The quality of the involved studies was relatively moderate. Pre-expansion, postexpansion, and postretention data were pooled. The nasal width, alar base width, and distances from the lower lips to the E line showed significant changes after expansion. Moreover, after retention, the nasal width, mouth width, upper philtrum width, and distance from the lower lip to the E line showed significant increases relative to the baseline values. Limitations of the present study included the moderate quality of the included studies and the fact that the results were based on short-term observations of patients in the growth phase.

Conclusion

Our findings suggest that RME results in a significantly increased nasal width, mouth width, upper philtrum width, and distance from the lower lip to the E line after the retention phase. However, the clinical importance of these findings is questionable.

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Efficient simulation of a low-profile visualized intraluminal support device: a novel fast virtual stenting technique

Abstract

Background

The low-profile visualized intraluminal support (LVIS) stent has become a promising endovascular option for treating intracranial aneurysms. To achieve better treatment of aneurysms using LVIS, we developed a fast virtual stenting technique for use with LVIS (F-LVIS) to evaluate hemodynamic changes in the aneurysm and validate its reliability.

Methods

A patient-specific aneurysm was selected for making comparisons between the real LVIS (R-LVIS) and the F-LVIS. To perform R-LVIS stenting, a hollow phantom based on a patient-specific aneurysm was fabricated using a three-dimensional printer. An R-LVIS was released in the phantom according to standard procedure. F-LVIS was then applied successfully in this aneurysm model. The computational fluid dynamics (CFD) values were calculated for both the F-LVIS and R-LVIS models. Qualitative and quantitative comparisons of the two models focused on hemodynamic parameters.

Results

The hemodynamic characteristics for R-LVIS and F-LVIS were well matched. Representative contours of velocities and wall shear stress (WSS) were consistently similar in both distribution and magnitude. The velocity vectors also showed high similarity, although the R-LVIS model showed faster and more fluid streams entering the aneurysm. Variation tendencies of the velocity in the aneurysm and the WSS on the aneurysm wall were also similar in the two models, with no statistically significant differences in either velocity or WSS.

Conclusions

The results of the computational hemodynamics indicate that F-LVIS is suitable for evaluating hemodynamic factors. This novel F-LVIS is considered efficient, practical, and effective.

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Targeting the psychosocial and functional fitness challenges of older adults with hearing loss: a participatory approach to adaptation of the walk and talk for your life program

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Impact of oral potentially malignant disorders on quality of life: a systematic review

Future Oncology, Ahead of Print.

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Micro-computed tomography-based anatomical study of the branch canals in mandibular anterior teeth in a Chinese population

Abstract

Objectives

To analyze the incidence and distribution of branch canals in mandibular anterior teeth.

Materials and methods

Results

Conclusions

There was regularity in the distribution and orientation of branch canals in mandibular anterior teeth.

Clinical relevance

This knowledge may be employed as a guide in clinical endodontic therapy.

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Correction to: Subcutaneous lipomas: A minimally invasive method for resection of subcutaneous lipomas preserving retaining ligaments

Abstract

The article Subcutaneous lipomas: A minimally invasivemethod for resection of subcutaneous lipomas preserving retaining ligaments, written by Akio Sakamoto, Takeshi Okamoto, Shuichi Matsuda, was originally published electronically on the publisher's internet portal (currently SpringerLink).

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Anti-hTERT siRNA-loaded nanoparticles block the growth of anaplastic thyroid cancer xenograft

The high frequency of hTERT-promoting mutations and the increased expression of hTERT mRNA in anaplastic thyroid cancer (ATC) make TERT a suitable molecular target for the treatment of this lethal neoplasm. In this study, we encapsulated an anti-hTERT oligonucleotide in biocompatible nanoparticles and analyzed the effects of this novel pharmaceutical preparation in preclinical models of ATC. Biocompatible nanoparticles were obtained in an acidified aqueous solution containing chitosan, anti-hTERT oligoRNAs and poloxamer 188 as a stabilizer. The effects of these anti-hTERT -nanoparticles (Na-siTERT) were tested in vitro on ATC cell lines (CAL-62 and 8505C) and in vivo on xenograft tumors obtained by flank injection of CAL-62 cells into SCID-mice. The Na-siTERT reduced the viability and migration of CAL-62 and 8505C cells after 48 h incubation. Intra-venous administration (every 48 h for 13 days) of this encapsulated drug in mice hosting a xenograft thyroid cancer determined a great reduction in the growth of the neoplasm (about 50% vs untreated animals or mice receiving empty nanoparticles), and decreased levels of Ki67 associated with lower hTERT expression. Moreover, the treatment resulted in minimal invasion of near-by tissues and reduced the vascularity of the xenograft tumor. No signs of toxicity appeared following this treatment. Telomere length was not modified by the Na-siTERT, indicating that the inhibitory effects of neoplasm growth was independent from the enzymatic telomerase function. These findings demonstrate the potential suitability of this anti-TERT nanoparticle formulation as a novel tool for ATC treatment.

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Kinetic and Equilibrium Sorption Studies of Ceftriaxone and Paracetamol by Surfactant-Modified Zeolite

Abstract

An organo-zeolite was prepared by loading hexadecyltrimethylammonium (HDTMA) onto clinoptilolite and was used to remove ceftriaxone sodium and paracetamol in aqueous solutions. Batch experiments were conducted to perform kinetics and sorption isotherms at 25 °C and 100 rpm. The results indicate that the equilibration times were 24 h for ceftriaxone sodium and 9 h for paracetamol. Furthermore, sorption capacities were 0.7288 and 0.0058 mg/g, respectively. The data were treatment with different models including pseudo first order, second order, and Elovich, the results suggested a chemical adsorption mechanism, and the adsorption equilibrium data for the two drugs show that they follow a linear trend, indicating a partitioning mechanism. Physicochemical properties such as solubility, log Kow, and pka play an important role in the adsorption process. Finally, the values obtained for zero charge point (ZPC) for zeolitic materials were 6.90, 6.94, and 6.90 for natural zeolite (ZN), sodium zeolite (ZNa), and zeolite modified surface at 30 mM HDTMA (ZMS-30), respectively.

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Sorption of Uranium on a Bifunctional Polymer of Diethylenetriaminepentaacetic Acid Cross-Linked β -Cyclodextrin in the Presence of Humic Acid: Kinetics, Isotherms, and Thermodynamics

Abstract

Humic acid (HA) plays an important role in the migration and transformation of uranium in natural waters. To effectively remove uranium in the presence of HA, a bifunctional polymer, diethylenetriaminepentaacetic acid cross-linked β-cyclodextrin (DTPA-β-CD), was synthesized by polycondensation reaction. The sorption performance of DTPA-β-CD in functions of pH, ionic strength, contact time, initial time, and temperature were explored batch wise. Experimental results showed that DTPA-β-CD could concurrently sorb uranium and HA around pH of 3.0. The sorption strongly depended on pH and on ionic strength, demonstrating outer-sphere surface complex in nature. Two sorption kinetics well followed pseudo-second-order model. Sorption isotherm accorded with Sips model. Increasing temperature facilitated uranium and restrained HA sorption. This work demonstrated that DTPA-β-CD was a promising material for sorbing uranium in the presence of HA.

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Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics, Published online: 22 March 2018; doi:10.1038/s41416-018-0034-9

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

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Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037, Published online: 22 March 2018; doi:10.1038/s41416-018-0047-4

Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

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A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma, Published online: 22 March 2018; doi:10.1038/s41416-018-0051-8

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

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The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma, Published online: 22 March 2018; doi:10.1038/s41416-018-0054-5

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

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Comment on ‘Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study’

Comment on 'Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study'

Comment on 'Clinical significance of <i>BRAF</i> non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study', Published online: 22 March 2018; doi:10.1038/s41416-018-0012-2

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer, Published online: 22 March 2018; doi:10.1038/s41416-018-0055-4

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

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Confocal Scanning Microscopy Provides Rapid, Detailed Intraoperative Histological Assessment of Brain Neoplasms: Experience with 106 Cases

Publication date: Available online 21 March 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Nikolay L. Martirosyan, Joseph Georges, Jennifer M. Eschbacher, Evgenii Belykh, Alessandro Carotenuto, Robert F. Spetzler, Peter Nakaji, Mark C. Preul
ObjectivesFrozen section histological analysis is currently the mainstay for intraprocedural tissue diagnosis during the resection of intracranial neoplasms and for evaluating tumor margins. However, frozen sections are time-consuming and often do not reveal the histological features needed for final diagnosis when compared with permanent sections. Confocal scanning microscopy (CSM) with certain stains may be a valuable technology that can add rapid and detailed histological assessment advantage for the neurosurgical operating room. This study describes potential advantages of CSM imaging of fresh human brain tumor tissues labeled with acriflavine (AF), acridine orange (AO) and cresyl violet (CV) within the neurosurgical operating room facility.Patients and Methods Acute slices from orthotopic human intracranial neoplasms were incubated with AF/AO and CV solutions for 10 seconds and 1 minute respectively. Samples were imaged using a bench-top CSM system. Histopathologic features of corresponding CSM and permanent hematoxylin and eosin images were reviewed for each case.ResultsOf 106 cases, 30 were meningiomas, 19 gliomas, 13 pituitary adenomas, 9 metastases, 6 schwannomas, 4 ependymomas, and 25 other pathologies. CSM with the addition of rapid fluorophores revealed striking microvascular, cellular and subcellular structures that correlated with conventional histology. By rapidly staining and optically sectioning freshly resected tissue, images were generated for intraoperative consultations in less than one minute. With this technique, an entire resected tissue sample was imaged and digitally stored for tele-pathology and archiving.ConclusionCSM of fresh human brain tumor tissue provides clinically meaningful and rapid histopathological assessment much faster than frozen section. With appropriate stains, including specific cellular structure or antibody staining, CSM could improve the timeliness of intraoperative decision-making, and the neurosurgical-pathology workflow during resection of human brain tumors, ultimately improving patient care.

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Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-cell Targets in Human IDH-Mutant Glioma

Purpose: Successful immunotherapies for IDH mut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. Experimental Design: Protein fractionations of tissue lysates from IDH mut gliomas (n=4) were performed. Fractions were tested by IFN-E; ELISpot assay for recognition through patient's T-cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico-predicted synthetic long-peptides in patients of origin, additional IDH mut glioma patients (n=16), and healthy donors (n=13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDH mut glioma stem-like cells (GSCs). HLA-A*02-restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T-cells by HLA-peptide tetramer analysis. Results: 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process 79 proteins were selected as potential T-cell antigens. 26 of these were recognized by the patients' T-cells and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDH mut glioma patients. Most immunogenic tumor-associated antigens (TAAs) were expressed in IDH mut gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02-restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T-cells in IDH mut glioma patients. Conclusion: By analyzing the repertoire of T-cell target antigens in IDH mut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDH mut tumors and GSCs.

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Induction of Telomere Dysfunction Prolongs Disease Control of Therapy-Resistant Melanoma

Purpose: Telomerase promoter mutations are highly prevalent in human tumors including melanoma. A subset of patients with metastatic melanoma often fail multiple therapies and there is an unmet and urgent need to prolong disease control for those patients. Experimental Design: Numerous pre-clinical therapy-resistant models of human and mouse melanoma were used to test the efficacy of a telomerase-directed nucleoside, 6-thio-2'-deoxyguanosine (6-thio-dG). Integrated transcriptomics and proteomics approaches were used to identify genes and proteins that were significantly down-regulated by 6-thio-dG. Results: We demonstrated the superior efficacy of 6-thio-dG both in vitro and in vivo that results in telomere dysfunction, leading to apoptosis and cell death in various pre-clinical models of therapy-resistant melanoma cells. 6-thio-dG concomitantly induces telomere dysfunction and inhibits the expression level of AXL. Conclusions: In summary, this study shows that indirectly targeting aberrant telomerase in melanoma cells with 6-thio-dG is a viable therapeutic approach in prolonging disease control and overcoming therapy resistance.

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A new approach to predict progression-free survival in stage IV EGFR-mutant NSCLC patients with EGFR-TKI therapy

Purpose: We established a computed tomography (CT)-derived approach to achieve accurate progression-free survival (PFS) prediction to EGFR tyrosine kinase inhibitors (TKIs) therapy in multicenter, stage IV EGFR-mutated non-small-cell lung cancer (NSCLC) patients. Experimental Design: 1032 CT-based phenotypic characteristics were extracted according to the intensity, shape and texture of NSCLC pre-therapy images. Based on these CT features extracted from 117 stage IV EGFR-mutant NSCLC patients, a CT-based phenotypic signature was proposed using a Cox regression model with LASSO penalty for the survival risk stratification of EGFR-TKI therapy. The signature was validated using two independent cohorts (101 and 96 patients, respectively). The benefit of EGFR-TKIs in stratified patients was then compared with another stage-IV EGFR-mutant NSCLC cohort only treated with standard chemotherapy (56 patients). Furthermore, an individualized prediction model incorporating the phenotypic signature and clinicopathologic risk characteristics was proposed for PFS prediction, and also validated by multicenter cohorts. Results: The signature consisted of 12 CT features demonstrated good accuracy for discriminating patients with rapid- and slow-progression to EGFR-TKI therapy in three cohorts (hazard ratio: 3.61, 3.77 and 3.67, respectively). Rapid-progression patients received EGFR TKIs did not show significant difference with patients underwent chemotherapy for progression-free survival benefit (p = 0.682). Decision curve analysis revealed that the proposed model significantly improved the clinical benefit compared with the clinicopathologic-based characteristics model (p < 0.0001). Conclusions:The proposed CT-based predictive strategy can achieve individualized prediction of PFS probability to EGFR-TKI therapy in NSCLCs, which holds promise of improving the pre-therapy personalized management of TKIs.

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The pattern of Mesenchymal stem cell expression is an independent marker of outcome in multiple myeloma.

Purpose: Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM. Experimental Design: To determine the impact of MSCs on MM outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in PCs or other cells present in BM aspirates. We then applied this MSC gene signature to whole BM biopsies of MM patients compared to healthy controls and determined MSC expression scores specific to MM and predictive of outcome. Results: We show that MM MSC gene expression signatures are able to differentiate MM from monoclonal gammopathy (MGUS) and smoldering MM (SMM) as well as from healthy controls and treated MM patients that have achieved a complete remission (CR). We identified a prognostic gene score based on three MSC specific genes COL4A1, NPR3 and ITGBL1, that was able to predict progression free survival (PFS) in MM patients and progression into MM from SMM. Conclusions: Our findings show that progression of MM and of SMM into MM not solely relies on intrinsic PC factors, but is independently impacted by the biology of the surrounding microenvironment.

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Ensartinib (X-396) in ALK-positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study

Purpose:Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC). Experimental Design: In dose escalation, ensartinib was administered at doses of 25–250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced ALK-positive NSCLC were administered 225 mg once daily. Patients who had received prior ALK TKI(s) and patients with brain metastases were allowed. Results: Thirty-seven patients enrolled in dose escalation, and 60 enrolled in dose expansion. The most common treatment-related toxicities were rash (56%), nausea (36%), pruritus (28%), vomiting (26%), and fatigue (22%); 23% of patients experienced a treatment-related Grade 3-4 toxicity (primarily rash and pruritus). The maximum tolerated dose was not reached, but the RP2D was chosen as 225 mg based on the frequency of rash observed at 250 mg without improvement in activity. Among the ALK-positive efficacy evaluable patients treated at ≥200 mg, the response rate (RR) was 60% and median progression-free survival (PFS) was 9.2 months. RR in ALK TKI naïve patients was 80% and median PFS was 26.2 months. In patients with prior crizotinib only, the RR was 69% and median PFS was 9.0 months. Responses were also observed in the central nervous system, with an intracranial RR of 64%. Conclusions: Ensartinib was active and generally well tolerated in patients with ALK-positive NSCLC.

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Validation of the oxygen desaturation index in the diagnostic workup of obstructive sleep apnea

Abstract

Introduction

Obstructive sleep apnea (OSA) is common, and diagnosis requires expensive and laborious testing to assess the apnea hypopnea index (AHI). We performed an analysis to explore the relationship between the oxygen desaturation index (ODI) as measured with pulse oximetry and the AHI in our large portable monitoring (PM) database to find an optimal cutoff value for the ODI in order to be able to exclude AHI ≥ 5 on PM.

Methods

Three thousand four hundred thirteen PM recordings were randomly divided into a training set (N = 2281) and a test set (N = 1132). The optimal cutoff for the ODI to exclude an AHI ≥ 5 on PM was determined in the training set and subsequently validated in the test set.

Results

Area under the curve of the ODI to exclude an AHI ≥ 5 on PM was 0.997 in the training set and 0.996 in the test set. In the training set, the optimal cutoff to predict an AHI < 5 was an ODI < 5. Using this cutoff in the test set provided a sensitivity of 97.7%, a specificity of 97.0%, a positive predictive value of 99.2%, and a negative predictive value of 91.4%.

Conclusion

An ODI < 5 predicts an AHI < 5 with high sensitivity and specificity when measured simultaneously using the same oximeter during PM recording.

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Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer patients: A prospective service development analysis

Publication date: Available online 21 March 2018
Source:Practical Radiation Oncology
Author(s): Sanjoy Chatterjee, Santam Chakraborty, Arunsingh Moses, Chandran Nallathambi, Anurupa Mahata, Samar Mandal, Rimpa Basu Achari, Indranil Mallick, Raj Kumar Shrimali, Tapesh Bhattacharyya, Sanjit Agrawal, Joydeep Ghosh, Rosina Ahmed
IntroductionUse of Deep Inspiration Breath Hold (DIBH) radiotherapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers.MethodsData regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiotherapy were compiled prospectively for all personnel (regarding person-hours, PH). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared to the DIBH plan. Mortality reduction due to use of DIBH was calculated using the years of life lost (YLLs) due to Ischemic Heart Disease (IHD) for Indians and the postulated reduction in risk of major cardiac events due to reduced cardiac dose.ResultsThe median reduction in mean heart dose (MHD) between the DIBH and FB plans was 166.7cGy (IQR: 62.7–257.4cGy). An extra 6.76 PH was required when implementing DIBH as compared to FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess YLLs due to IHD if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left sided breast cancers at 2.3 times the annual per-capita GDP.ConclusionAlthough routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

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Novel Magnetic Nanocarbon and Its Adsorption of Hg and Pb from Water

Abstract

Lead and mercury are two of the most toxic heavy metals in environments. Mesosilicate-templated magnetic nanocarbons with ascorbic acid as carbon precursor were developed through nanocasting processes. The nanocarbon showed effective magnetic separation and the maximum adsorption capacity of 80.6 and 66.3 mg/g for Hg and Pb, respectively. Langmuir model well described adsorption processes of both Hg and Pb from water. Magnetic nanocarbon could be easily separated and incinerated, reducing the volume requiring the disposal. This study indicates that mesosilicate-templated nanocarbons with easy disposal potentials may be good candidates for cleansing Hg and Pb from contaminated water.

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A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma

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Trends and projections in adenocarcinoma and squamous cell carcinoma of the oesophagus in England from 1971 to 2037

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Comment on ‘Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study’

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The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

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In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics

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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

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Reply to `Comment on `Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study''

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Validation of the oxygen desaturation index in the diagnostic workup of obstructive sleep apnea

Abstract

Introduction

Methods

Results

Conclusion

An ODI < 5 predicts an AHI < 5 with high sensitivity and specificity when measured simultaneously using the same oximeter during PM recording.

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Effect of age and hearing loss on auditory stream segregation of speech sounds

Publication date: Available online 21 March 2018
Source:Hearing Research
Author(s): Marion David, Alexis N. Tausend, Olaf Strelcyk, Andrew J. Oxenham
Segregating and understanding speech in complex environments is a major challenge for hearing-impaired (HI) listeners. It remains unclear to what extent these difficulties are dominated by direct interference, such as simultaneous masking, or by a failure of the mechanisms of stream segregation. This study compared HI listeners' performance with that of young and age-matched normal-hearing (NH) listeners in stream segregation tasks involving speech sounds. Listeners were presented with sequences of speech tokens, each consisting of a fricative consonant and a voiced vowel (CV). The CV tokens were concatenated into interleaved sequences that alternated in fundamental frequency (F0) and/or simulated vocal tract length (VTL). Each pair of interleaved sequences was preceded by a "word" consisting of two random tokens. The listeners were asked to indicate whether the word was present in the following interleaved sequences. The word, if present, occurred within one of the interleaved sequences, so that performance improved if the listeners were able to perceptually segregate the two sequences. Although HI listeners' identification of the speech tokens in isolation was poorer than that of the NH listeners, HI listeners with both mild and moderate hearing loss were generally able to use both F0 and VTL cues to segregate the interleaved sequences. The results suggest that the difficulties experienced by HI listeners in complex acoustic environments cannot be explained by a loss of basic stream segregation abilities.

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National DNA Day!

It is fitting that this year's Academy Research Conference, "Genetics & Hearing Loss" falls exactly one week prior to National DNA Day, April 25.

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FDA Issues Update on Rare Breast Implant-Associated Lymphoma

As of September 30, 2017, the FDA has received a total of 414 medical device reports of anaplastic large cell lymphoma associated with breast implants, most involving implants with textured surfaces.
News Alerts

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The Use Of Buccal Fat Pad In Surgical Treatment Of ‘Krokodil’ Drug-Related Osteonecrosis Of Maxilla

Publication date: Available online 20 March 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Koryun Hakobyan, Yuri Poghosyan, Aram Kasyan
'Krokodil' is the street name of a new synthetic drug mixture. It is a light brown liquid that is used intravenously without previous purification. Osteonecrosis of the jaw (ONJ) is a common complication among Krokodil users. Krokodil drug-related ONJ presents as alveolar process exposure in the oral cavity.Surgery is the main method for treatment of Krokodil drug-related ONJ patients. In a study by Poghosyan et al., no cases of recurrence were seen after surgery on the maxilla, but 38% of cases (8/21) developed an oroantral communication after surgical treatment for maxillary osteonecrosis (Poghosyan et al., 2014).The aim of this study is to report on the results of buccal fat pad use in closure of maxillary sinus floor defects after partial maxillary resection in Krokodil drug-related ONJ patients.Six male patients with Krokodil drug-related distal maxillary osteonecrosis were included in this retrospective study. All patients underwent surgical treatment, which included surgical removal of necrotic bone, and closure of formed maxillary sinus floor defects with buccal fat pad and local mucoperiosteal flaps.In all patients the postoperative period was uneventful. After suture removal small areas of buccal fad pad exposure were found in all patients, which epithelialized successfully over the following month. During the postoperative follow-up period (8–12 months) no signs of recurrence were found.

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Supportive topical tranexamic acid application for hemostasis in oral bleeding events – retrospective cohort study of 542 patisents

Publication date: Available online 20 March 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Matthias Zirk, Max Zinser, Johannes Buller, Viktor Bilinsky, Timo Dreiseidler, Joachim E. Zöller, Matthias Kreppel
PurposeTranexamic acid (TXA) is widely used in the prevention of postsurgical oral bleeding. Tranexamic acid in addition to further surgical measures is widely utilized in prevention of post-surgical oral bleeding. The aim of the present study was to investigate: Can oral hemostasis be achieved by merely compression and topical application of tranexamic acid in different anticoagulant regimes among patients attending a general emergency department? Where are the limits to this procedure? Which has the greater impact on surgeons' choice for an invasive hemostatic approach—bleeding quality or oral anticoagulant therapy?Materials and methodsA retrospective cohort study of 542 patients who consecutively received treatment for oral bleeding was performed. We surveyed the values of the diverse hemostatic approaches. Special attention was granted to patient anticoagulant regimen and quality of the oral bleeding event.ResultsA total of 199 of 542 (36.7%) oral bleeding events were stopped by compression with a gauze or gauze soaked with TXA (4.8%). Stopping an oral bleeding event with wound compression can be improved by factor 1.6 if the gauze is soaked with tranexamic acid (4.8%), p ≤ 0.05. LMWH presented significantly more moderate bleeding than bloody oozing of the wound, p<0.05. The quality of bleeding had a strong influence on oral surgeons' decisions to apply further surgical means. Sutures and native collagen fleeces were the favored methods to stop moderate and severe bleeding (p<0.05).ConclusionTopical application of TXA aids as a useful supportive tool to stop mild bleeding events such as the bloody oozing of an oral wound. The quality of an oral bleeding episode should be considered in the choice of hemostatic measure. Hemostatic approaches should begin with the least invasive procedure. TXA is a helpful tool.

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Cancers, Vol. 10, Pages 88: Use of the Ion PGM and the GeneReader NGS Systems in Daily Routine Practice for Advanced Lung Adenocarcinoma Patients: A Practical Point of View Reporting a Comparative Study and Assessment of 90 Patients

Cancers, Vol. 10, Pages 88: Use of the Ion PGM and the GeneReader NGS Systems in Daily Routine Practice for Advanced Lung Adenocarcinoma Patients: A Practical Point of View Reporting a Comparative Study and Assessment of 90 Patients

Cancers doi: 10.3390/cancers10040088

Authors: Simon Heeke Véronique Hofman Elodie Long-Mira Virginie Lespinet Salomé Lalvée Olivier Bordone Camille Ribeyre Virginie Tanga Jonathan Benzaquen Sylvie Leroy Charlotte Cohen Jérôme Mouroux Charles Marquette Marius Ilié Paul Hofman

Background: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform. Methods: Clinical samples from 90 patients (60 Retrospectively and 30 Prospectively) with lung adenocarcinoma were sequenced with both systems. Mutations were analyzed and EGFR, KRAS, BRAF, NRAS, ALK, PIK3CA and ERBB2 genes were compared and sampling time and suitability for clinical testing were assessed. Results: Both sequencing systems showed perfect concordance for the overlapping genes. Correlation of allele frequency was r2 = 0.93 for the retrospective patients and r2 = 0.81 for the prospective patients. Hands-on time and total run time were shorter using the PGM system, while the GeneReader platform provided good traceability and up-to-date interpretation of the results. Conclusion: We demonstrated the suitability of the GeneReader NGS system in routine practice in a clinical pathology laboratory setting.

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Wheat amylase/trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice

Publication date: Available online 21 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Iris Bellinghausen, Benno Weigmann, Victor Zevallos, Joachim Maxeiner, Sonja Reißig, Ari Waisman, Detlef Schuppan, Joachim Saloga
BackgroundAmylase-trypsin inhibitors (ATIs) in wheat and related cereals are potent activators of myeloid innate immune cells via engagement of TLR4. Furthermore, ATIs have been shown to serve as adjuvants in experimental intestinal inflammatory diseases.ObjectiveThe aim of this study was to analyze whether ATIs are also modifiers of allergic inflammation.MethodsTherefore, CD4⁺ T cells from grass or birch pollen sensitized donors were stimulated with autologous allergen-pulsed dendritic cells in the presence or absence of ATIs or the control storage protein zein from corn. To analyze allergen-induced gut and lung inflammation, immunodeficient mice were engrafted with PBMC from these allergic donors plus the respective allergen, and fed with selected diets. Three weeks later, inflammation was induced by rectal or intranasal allergen challenge and monitored by mini-endoscopy or airway hyperreactivity (AHR), respectively.ResultsAllergen-specific T cell proliferation and cytokine production was significantly exacerbated by ATIs and not by zein. In vivo, allergen-specific human IgE was strongly elevated in sera of mice receiving an ATI-containing diet compared to mice that were fed gluten- and thus ATI-free. Importantly, allergen-induced IgE-dependent colitis and AHR were also enhanced in ATI-fed mice. Gut inflammation was further increased in mice receiving an additional ATI injection and even detectable in the absence of the aeroallergen, while zein had no such effect. Injection of anti-human TLR4 mAbs or the anti-human IgE mAb omalizumab completely abolished ATI-induced allergic inflammation.ConclusionThese results underline that wheat ATIs are important nutritional activators and adjuvants of allergy which might be exploited for nutritional therapeutic strategies.Clinical ImplicationsAllergen-induced IgE-mediated inflammation of the intestine and the lung is exacerbated by ATIs which might be important for future therapies.

Graphical abstract

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Effect of age and hearing loss on auditory stream segregation of speech sounds

Editorial Board

Publication date: March 2018
Source:Gait & Posture, Volume 61

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Fluctuating Hearing Loss in the Only Hearing Ear: Cochlear Implantation in the Contralateral Deaf Side.

Fluctuating Hearing Loss in the Only Hearing Ear: Cochlear Implantation in the Contralateral Deaf Side.

Otolaryngol Head Neck Surg. 2018 Mar 01;:194599818763137

Authors: Russo FY, De Seta D, Lahlou G, Borel S, Nguyen Y, Bouccara D, Sterkers O, Bernardeschi D, Mosnier I

Abstract
Objective To investigate the hearing performance of adult patients presenting unilateral deafness with contralateral fluctuating hearing loss who received a cochlear implant on the deaf side. Study Design Case series with chart review. Setting University tertiary referral center. Subjects and Methods Preoperatively and at 6 and 12 months postoperatively, 23 patients underwent pure tone audiometry and speech audiometry with disyllabic and monosyllabic words in a quiet environment and sentences in quiet and noisy (signal-to-noise ratio +10 dB SPL) environments under best-aided conditions. The Abbreviated Profile of Hearing Aid Benefit (APHAB) inventory was evaluated preoperatively and at 6 and 12 months postoperatively. Results No difference was found between pre- and postoperative tests for disyllabic and monosyllabic words. For sentences in quiet and noisy environments, a difference between pre- and postoperative performance was present at 1 year ( P = .002 and P = .02, respectively). In a noisy environment, a difference was present at 6 and 12 months postoperatively as compared with the preoperative value (mean ± SD: 6 months: 42% ± 7.1% vs 61% ± 6.5%, P = .016). A significant improvement in the APHAB score was found at 6 and 12 months postimplantation (Friedman's 2-way analysis of variance by ranks, P < .001). The number of years of hearing deprivation of the deaf ear was not correlated with performance. Conclusion When incapacitating fluctuating hearing loss occurs in patients presenting a contralateral deaf ear, a cochlear implant is indicated in the latter ear, significantly improving performance in noisy conditions and allowing a better quality of communication to be achieved.

PMID: 29557301 [PubMed - as supplied by publisher]

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Evaluation of selective attention in patients with misophonia

Publication date: Available online 21 March 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Fúlvia Eduarda da Silva, Tanit Ganz Sanchez
IntroductionMisophonia is characterized by the aversion to very selective sounds, which evoke a strong emotional reaction. It has been inferred that misophonia, as well as tinnitus, is associated with hyperconnectivity between auditory and limbic systems. Individuals with bothersome tinnitus may have selective attention impairment, but it has not been demonstrated in case of misophonia yet.ObjectiveTo characterize a sample of misophonic subjects and compare it with two control groups, one with tinnitus individuals (without misophonia) and the other with asymptomatic individuals (without misophonia and without tinnitus), regarding the selective attention.MethodsWe evaluated 40 normal-hearing participants: 10 with misophonia, 10 with tinnitus (without misophonia) and 20 without tinnitus and without misophonia. In order to evaluate the selective attention, the dichotic sentence identification test was applied in three situations: firstly, the Brazilian Portuguese test was applied. Then, the same test was applied, combined with two competitive sounds: chewing sound (representing a sound that commonly triggers misophonia), and white noise (representing a common type of tinnitus which causes discomfort to patients).ResultsThe dichotic sentence identification test with chewing sound, showed that the average of correct responses differed between misophonia and without tinnitus and without misophonia (p=0.027) and between misophonia and tinnitus (without misophonia) (p=0.002), in both cases lower in misophonia. Both, the dichotic sentence identification test alone, and with white noise, failed to show differences in the average of correct responses among the three groups (p≥0.452).ConclusionThe misophonia participants presented a lower percentage of correct responses in the dichotic sentence identification test with chewing sound; suggesting that individuals with misophonia may have selective attention impairment when they are exposed to sounds that trigger this condition.

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The Use Of Buccal Fat Pad In Surgical Treatment Of ‘Krokodil’ Drug-Related Osteonecrosis Of Maxilla

Supportive topical tranexamic acid application for hemostasis in oral bleeding events – retrospective cohort study of 542 patisents

Maxillary tumour-induced osteomalacia

Publication date: Available online 21 March 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): O. Emodi, A. Rachmiel, D. Tiosano, R.M. Nagler
Tumour-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phosphate wasting that results in severe hypophosphatemia, defective vitamin D metabolism, and osteomalacia. In the case reported here, maxillary TIO was not diagnosed for 6years, although initial complaints were reported when the patient was 12years old. Meanwhile she suffered from profound growth limitation, pain, weakness, and spontaneous multiple bone fractures, culminating in complete loss of ambulatory ability and severe limitation in daily activities. At age 18years, she finally received an accurate diagnosis and definitive treatment was administered. She underwent a partial maxillectomy with complete removal of the tumour, resulting in a full cure. Shortly afterwards the patient regained the ability to walk, no longer needing the wheelchair to which she had been confined. This definitive diagnosis was based on three modalities: (1) fibroblast growth factor 23 analysis (high levels of the secreted hormone were found on the left side of the maxilla in the facial vein and pterygoid plexus, pinpointing the tumour location), (2) octreotide scan, and (3) ⁶⁸Ga-DOTA-NOC-PET/CT. TIO removal via partial maxillectomy led to a complete reversal of this patient's health condition, restoring her ability to walk and function. The importance of prompt employment of these diagnostic modalities and the high level of clinical suspicion required in such cases are clear.

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Facial soft tissue changes after nonsurgical rapid maxillary expansion: a systematic review and meta-analysis

Long-Term Neuroinflammation Induced by Influenza A Virus Infection and the Impact on Hippocampal Neuron Morphology and Function

Acute influenza infection has been reported to be associated with neurological symptoms. However, the long-term consequences of an infection with neurotropic and non-neurotropic influenza A virus (IAV) variants for the CNS remain elusive. We can show that spine loss in the hippocampus after infection with neurotropic H7N7 (rSC35M) and non-neurotropic H3N2 (maHK68) in female C57BL/6 mice persists well beyond the acute phase of the disease. Although spine number was significantly reduced at 30 d postinfection (dpi) with H7N7 or H3N2, full recovery could only be observed much later at 120 dpi. Infection with H1N1 virus, which was shown previously to affect spine number and hippocampus-dependent learning acutely, had no significant long-term effects. Spine loss was associated with an increase in the number of activated microglia, reduced long-term potentiation in the hippocampus, and impairment in spatial memory formation, indicating that IAV-associated inflammation induced functional and structural alterations in hippocampal networks. Transcriptome analyses revealed regulation of many inflammatory and neuron- and glia-specific genes in H3N2- and H7N7-infected mice at day 18 and in H7N7-infected mice at day 30 pi that related to the structural and functional alterations. Our data provide evidence that neuroinflammation induced by neurotropic H7N7 and infection of the lung with a non-neurotropic H3N2 IAV result in long-term impairments in the CNS. IAV infection in humans may therefore not only lead to short-term responses in infected organs, but may also trigger neuroinflammation and associated chronic alterations in the CNS.

SIGNIFICANCE STATEMENT In the acute phase of influenza infection, neuroinflammation can lead to alterations in hippocampal neuronal morphology and cognitive deficits. The results of this study now also provide evidence that neuroinflammation induced by influenza A virus (IAV) infection can induce longer-lasting, virus-specific alterations in neuronal connectivity that are still detectable 1 month after infection and are associated with impairments in spatial memory formation. IAV infection in humans may therefore not only lead to short-term responses in infected organs, but may also trigger neuroinflammation and associated chronic alterations in the CNS.

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Alzheimer's Disease and Sleep-Wake Disturbances: Amyloid, Astrocytes, and Animal Models

Sleep–wake abnormalities are common in patients with Alzheimer's disease, and can be a major reason for institutionalization. However, an emerging concept is that these sleep–wake disturbances are part of the causal pathway accelerating the neurodegenerative process. Recently, new findings have provided intriguing evidence for a positive feedback loop between sleep–wake dysfunction and β-amyloid (Aβ) aggregation. Studies in both humans and animal models have shown that extended periods of wakefulness increase Aβ levels and aggregation, and accumulation of Aβ causes fragmentation of sleep. This perspective is aimed at presenting evidence supporting causal links between sleep–wake dysfunction and aggregation of Aβ peptide in Alzheimer's disease, and explores the role of astrocytes, a specialized type of glial cell, in this context underlying Alzheimer's disease pathology. The utility of current animal models and the unexplored potential of alternative animal models for testing mechanisms involved in the reciprocal relationship between sleep disruption and Aβ are also discussed.

Dual Perspectives Companion Paper: Microglia-Mediated Synapse Loss in Alzheimer's Disease by Lawrence Rajendran and Rosa Paolicelli

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This Week in The Journal

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Microglia-Mediated Synapse Loss in Alzheimer's Disease

Microglia are emerging as key players in neurodegenerative diseases, such as Alzheimer's disease (AD). Thus far, microglia have rather been known as modulator of neurodegeneration with functions limited to neuroinflammation and release of neurotoxic molecules. However, several recent studies have demonstrated a direct role of microglia in "neuro" degeneration observed in AD by promoting phagocytosis of neuronal, in particular, synaptic structures. While some of the studies address the involvement of the β-amyloid peptides in the process, studies also indicate that this could occur independent of amyloid, further elevating the importance of microglia in AD. Here we review these recent studies and also speculate about the possible cellular mechanisms, and how they could be regulated by risk genes and sleep. Finally, we deliberate on possible avenues for targeting microglia-mediated synapse loss for therapy and prevention.

Dual Perspectives Companion Paper: Alzheimer's Disease and Sleep-Wake Disturbances: Amyloid, Astrocytes, and Animal Models by William M. Vanderheyden, Miranda M. Lim, Erik S. Musiek, and Jason R. Gerstner

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Visual Working Memory Is Independent of the Cortical Spacing Between Memoranda

The sensory recruitment hypothesis states that visual short-term memory is maintained in the same visual cortical areas that initially encode a stimulus' features. Although it is well established that the distance between features in visual cortex determines their visibility, a limitation known as crowding, it is unknown whether short-term memory is similarly constrained by the cortical spacing of memory items. Here, we investigated whether the cortical spacing between sequentially presented memoranda affects the fidelity of memory in humans (of both sexes). In a first experiment, we varied cortical spacing by taking advantage of the log-scaling of visual cortex with eccentricity, presenting memoranda in peripheral vision sequentially along either the radial or tangential visual axis with respect to the fovea. In a second experiment, we presented memoranda sequentially either within or beyond the critical spacing of visual crowding, a distance within which visual features cannot be perceptually distinguished due to their nearby cortical representations. In both experiments and across multiple measures, we found strong evidence that the ability to maintain visual features in memory is unaffected by cortical spacing. These results indicate that the neural architecture underpinning working memory has properties inconsistent with the known behavior of sensory neurons in visual cortex. Instead, the dissociation between perceptual and memory representations supports a role of higher cortical areas such as posterior parietal or prefrontal regions or may involve an as yet unspecified mechanism in visual cortex in which stimulus features are bound to their temporal order.

SIGNIFICANCE STATEMENT Although much is known about the resolution with which we can remember visual objects, the cortical representation of items held in short-term memory remains contentious. A popular hypothesis suggests that memory of visual features is maintained via the recruitment of the same neural architecture in sensory cortex that encodes stimuli. We investigated this claim by manipulating the spacing in visual cortex between sequentially presented memoranda such that some items shared cortical representations more than others while preventing perceptual interference between stimuli. We found clear evidence that short-term memory is independent of the intracortical spacing of memoranda, revealing a dissociation between perceptual and memory representations. Our data indicate that working memory relies on different neural mechanisms from sensory perception.

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Expression of Bona Fide Epithelial Stem Cell Marker in Postmitotic Olfactory Bulb Neurons Suggest Novel Roles for Wnt Signaling in the Brain

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Dendritic A-Current in Rhythmically Active PreBötzinger Complex Neurons in Organotypic Cultures from Newborn Mice

The brainstem preBötzinger complex (preBötC) generates the inspiratory rhythm for breathing. The onset of neural activity that precipitates the inspiratory phase of the respiratory cycle may depend on the activity of type-1 preBötC neurons, which exhibit a transient outward K⁺ current, I_A. Inspiratory rhythm generation can be studied ex vivo because the preBötC remains rhythmically active in vitro, both in acute brainstem slices and organotypic cultures. Advantageous optical conditions in organotypic slice cultures from newborn mice of either sex allowed us to investigate how I_A impacts Ca²⁺ transients occurring in the dendrites of rhythmically active type-1 preBötC neurons. The amplitude of dendritic Ca²⁺ transients evoked via voltage increases originating from the soma significantly increased after an I_A antagonist, 4-aminopyridine (4-AP), was applied to the perfusion bath or to local dendritic regions. Similarly, glutamate-evoked postsynaptic depolarizations recorded at the soma increased in amplitude when 4-AP was coapplied with glutamate at distal dendritic locations. We conclude that I_A is expressed on type-1 preBötC neuron dendrites. We propose that I_A filters synaptic input, shunting sparse excitation, while enabling temporally summated events to pass more readily as a result of I_A inactivation. Dendritic I_A in rhythmically active preBötC neurons could thus ensure that inspiratory motor activity does not occur until excitatory synaptic drive is synchronized and well coordinated among cellular constituents of the preBötC during inspiratory rhythmogenesis. The biophysical properties of dendritic I_A might thus promote robustness and regularity of breathing rhythms.

SIGNIFICANCE STATEMENT Brainstem neurons in the preBötC generate the oscillatory activity that underlies breathing. PreBötC neurons express voltage-dependent currents that can influence inspiratory activity, among which is a transient potassium current (I_A) previously identified in a rhythmogenic excitatory subset of type-1 preBötC neurons. We sought to determine whether I_A is expressed in the dendrites of preBötC. We found that dendrites of type-1 preBötC neurons indeed express I_A, which may aid in shunting sparse non-summating synaptic inputs, while enabling strong summating excitatory inputs to readily pass and thus influence somatic membrane potential trajectory. The subcellular distribution of I_A in rhythmically active neurons of the preBötC may thus be critical for producing well coordinated ensemble activity during inspiratory burst formation.

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Subretinal Human Umbilical Tissue-Derived Cell Transplantation Preserves Retinal Synaptic Connectivity and Attenuates Müller Glial Reactivity

Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidated. Subretinal administration of hUTC preserves visual function in the Royal College of Surgeons (RCS) rat, a genetic model of retinal degeneration caused by Mertk loss of function. hUTC secrete synaptogenic and neurotrophic factors that improve the health and connectivity of the neural retina. Therefore, we investigated the progression of synapse and photoreceptor loss and whether hUTC treatment preserves photoreceptors and synaptic connectivity in the RCS rats of both sexes. We found that RCS retinas display significant deficits in synaptic development already by postnatal day 21 (P21), before the onset of photoreceptor degeneration. Subretinal transplantation of hUTC at P21 is necessary to rescue visual function in RCS rats, and the therapeutic effect is enhanced with repeated injections. Synaptic development defects occurred concurrently with morphological changes in Müller glia, the major perisynaptic glia in the retina. hUTC transplantation strongly diminished Müller glia reactivity and specifically protected the α2-1-containing retinal synapses, which are responsive to thrombospondin family synaptogenic proteins secreted by Müller glia. Müller glial reactivity and reduced synaptogenesis observed in RCS retinas could be recapitulated by CRISPR/Cas9-mediated loss-of-Mertk in Müller glia in wild-type rats. Together, our results show that hUTC transplantation supports the health of retina at least in part by preserving the functions of Müller glial cells, revealing a previously unknown aspect of hUTC transplantation-based therapy.

SIGNIFICANCE STATEMENT Despite the promising effects observed in clinical trials and preclinical studies, how subretinal human umbilical tissue-derived cell (hUTC) transplantation mediates vision improvements is not fully known. Using a rat model of retinal degeneration, the RCS rat (lacking Mertk), here we provide evidence that hUTC transplantation protects visual function and health by protecting photoreceptors and preserving retinal synaptic connectivity. Furthermore, we find that loss of Mertk function only in Müller glia is sufficient to impair synaptic development and cause activation of Müller glia. hUTC transplantation strongly attenuates the reactivity of Müller glia in RCS rats. These findings highlight novel cellular and molecular mechanisms within the neural retina, which underlie disease mechanisms and pinpoint Müller glia as a novel cellular target for hUTC transplantation.

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Detecting Unattended Stimuli Depends on the Phase of Prestimulus Neural Oscillations

Neural oscillations appear important for perception and attention processes because stimulus detection is dependent upon the phase of 7–11 Hz oscillations before stimulus onset. Previous work has examined stimulus detection at attended locations, but it is unknown whether unattended locations are also subject to phasic modulation by ongoing oscillatory activity, as would be predicted by theories proposing a role for neural oscillations in organizing general neural processing. Here, we recorded brain activity with EEG while human participants of both sexes detected brief visual targets preceded by a spatial cue and determined whether performance for cued (attended) and uncued (unattended) targets was influenced by oscillatory phase across a range of frequencies. Detection of both attended and unattended targets depended upon an ~5 Hz theta rhythm and an ~11–15 Hz alpha rhythm. Critically, detection of unattended stimuli was more strongly modulated by the phase of theta oscillations than was detection of attended stimuli, suggesting that attentional allocation involves a disengagement from ongoing theta sampling. There was no attention-related difference in the strength of alpha phase dependence, consistent with a perceptual rather than attentional role of oscillatory phase in this frequency range. These results demonstrate the importance of neural oscillations in modulating visual processing at both attended and unattended locations and clarify one way in which attention may produce its effects: through disengagement from low-frequency sampling at attended locations.

SIGNIFICANCE STATEMENT Past work on the interaction between oscillatory phase and neural processing has shown the involvement of posterior ~7–11 Hz oscillations in visual processing. Most studies, however, have presented stimuli at attended locations, making it difficult to disentangle frequencies related to attention from those related to perception. Here, we compared the oscillatory frequencies involved in the detection of attended and unattended stimuli and found that ~11–15 Hz oscillations were related to perception independently of attention, whereas ~5 Hz oscillations were more prominent for the detection of unattended stimuli. This work demonstrates the importance of neural oscillations for mediating stimulus processing at both attended and unattended locations and clarifies the different oscillatory frequencies involved in attention and perception.

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Neurobiological Mechanisms of Responding to Injustice

People are particularly sensitive to injustice. Accordingly, deeper knowledge regarding the processes that underlie the perception of injustice, and the subsequent decisions to either punish transgressors or compensate victims, is of important social value. By combining a novel decision-making paradigm with functional neuroimaging, we identified specific brain networks that are involved with both the perception of, and response to, social injustice, with reward-related regions preferentially involved in punishment compared with compensation. Developing a computational model of punishment allowed for disentangling the neural mechanisms and psychological motives underlying decisions of whether to punish and, subsequently, of how severely to punish. Results show that the neural mechanisms underlying punishment differ depending on whether one is directly affected by the injustice, or whether one is a third-party observer of a violation occurring to another. Specifically, the anterior insula was involved in decisions to punish following harm, whereas, in third-party scenarios, we found amygdala activity associated with punishment severity. Additionally, we used a pharmacological intervention using oxytocin, and found that oxytocin influenced participants' fairness expectations, and in particular enhanced the frequency of low punishments. Together, these results not only provide more insight into the fundamental brain mechanisms underlying punishment and compensation, but also illustrate the importance of taking an explorative, multimethod approach when unraveling the complex components of everyday decision-making.

SIGNIFICANCE STATEMENT The perception of injustice is a fundamental precursor to many disagreements, from small struggles at the dinner table to wasteful conflict between cultures and countries. Despite its clear importance, relatively little is known about how the brain processes these violations. Taking an interdisciplinary approach, we combine methods from neuroscience, psychology, and economics to explore the neurobiological mechanisms involved in both the perception of injustice as well as the punishment and compensation decisions that follow. Using a novel behavioral paradigm, we identified specific brain networks, developed a computational model of punishment, and found that administrating the neuropeptide oxytocin increases the administration of low punishments of norm violations in particular. Results provide valuable insights into the fundamental neurobiological mechanisms underlying social injustice.

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Correction: Araujo et al., "Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity"

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Human Sensorimotor Cortex Control of Directly Measured Vocal Tract Movements during Vowel Production

During speech production, we make vocal tract movements with remarkable precision and speed. Our understanding of how the human brain achieves such proficient control is limited, in part due to the challenge of simultaneously acquiring high-resolution neural recordings and detailed vocal tract measurements. To overcome this challenge, we combined ultrasound and video monitoring of the supralaryngeal articulators (lips, jaw, and tongue) with electrocorticographic recordings from the cortical surface of 4 subjects (3 female, 1 male) to investigate how neural activity in the ventral sensory-motor cortex (vSMC) relates to measured articulator movement kinematics (position, speed, velocity, acceleration) during the production of English vowels. We found that high-gamma activity at many individual vSMC electrodes strongly encoded the kinematics of one or more articulators, but less so for vowel formants and vowel identity. Neural population decoding methods further revealed the structure of kinematic features that distinguish vowels. Encoding of articulator kinematics was sparsely distributed across time and primarily occurred during the time of vowel onset and offset. In contrast, encoding was low during the steady-state portion of the vowel, despite sustained neural activity at some electrodes. Significant representations were found for all kinematic parameters, but speed was the most robust. These findings enabled by direct vocal tract monitoring demonstrate novel insights into the representation of articulatory kinematic parameters encoded in the vSMC during speech production.

SIGNIFICANCE STATEMENT Speaking requires precise control and coordination of the vocal tract articulators (lips, jaw, and tongue). Despite the impressive proficiency with which humans move these articulators during speech production, our understanding of how the brain achieves such control is rudimentary, in part because the movements themselves are difficult to observe. By simultaneously measuring speech movements and the neural activity that gives rise to them, we demonstrate how neural activity in sensorimotor cortex produces complex, coordinated movements of the vocal tract.

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Αρχειοθήκη ιστολογίου

Τετάρτη 21 Μαρτίου 2018

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