Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τετάρτη 29 Μαρτίου 2017

Effects of Simulated Hearing Loss on Bilingual Children's Consonant Recognition in Noise.

Objective: This study investigated the possible impact of simulated hearing loss on speech perception in Spanish-English bilingual children. To avoid confound between individual differences in hearing-loss configuration and linguistic experience, threshold-elevating noise simulating a mild-to-moderate sloping hearing loss was used with normal-hearing listeners. The hypotheses were that: (1) bilingual children can perform similarly to English-speaking monolingual peers in quiet; (2) for both bilingual and monolingual children, noise and simulated hearing loss would have detrimental impacts consistent with their acoustic characteristics (i.e., consonants with high-frequency cues remain highly intelligible in speech-shaped noise, but suffer from simulated hearing loss more than other consonants); (3) differences in phonology and acquisition order between Spanish and English would have additional negative influence on bilingual children's recognition of some English consonants. Design: Listeners were 11 English-dominant, Spanish-English bilingual children (6 to 12 years old) and 12 English-speaking, monolingual age peers. All had normal hearing and age-appropriate nonverbal intelligence and expressive English vocabulary. Listeners performed a listen-and-repeat speech perception task. Targets were 13 American English consonants embedded in vowel-consonant-vowel (VCV) syllables. VCVs were presented in quiet and in speech-shaped noise at signal-to-noise ratios (SNRs) of -5, 0, 5 dB (normal-hearing condition). For the simulated hearing-loss condition, threshold-elevating noise modeling a mild-to-moderate sloping sensorineural hearing loss profile was added to the normal-hearing stimuli for 0, 5 dB SNR, and quiet. Responses were scored for consonant correct. Individual listeners' performance was summarized for average across 13 consonants (overall) and for individual consonants. Results: Groups were compared for the effects of background noise and simulated hearing loss. As predicted, group performed similarly in quiet. The simulated hearing loss had a considerable detrimental impact on both groups, even in the absence of speech-shaped noise. Contrary to our prediction, no group difference was observed at any SNR in either condition. However, although nonsignificant, the greater within-group variance for the bilingual children in the normal-hearing condition indicated a wider "normal" range than for the monolingual children. Interestingly, although it did not contribute to the group difference, bilingual children's overall consonant recognition in both conditions improved with age, whereas such a developmental trend for monolingual children was observed only in the simulated hearing-loss condition, suggesting possible effects of experience. As for the recognition of individual consonants, the influence of background noise or simulated hearing loss was similar between groups and was consistent with the prediction based on their acoustic characteristics. Conclusions: The results demonstrated that school-age, English-dominant, Spanish-English bilingual children can recognize English consonants in a background of speech-shaped noise with similar average accuracy as English-speaking monolingual age peers. The general impact of simulated hearing loss was also similar between bilingual and monolingual children. Thus, our hypothesis that bilingual children's English consonant recognition would suffer from background noise or simulated hearing loss more than the monolingual peers was rejected. However, the present results raise several issues that warrant further investigation, including the possible difference in the "normal" range for bilingual and monolingual children, influence of experience, impact of actual hearing loss on bilingual children, and stimulus quality. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Early Hearing Detection and Intervention-Pediatric Audiology Links to Services EHDI-PALS: Building a National Facility Database.

Objectives: To create a searchable web-based national audiology facility directory using a standardized survey, so parents and providers could identify which facilities had capacity to provide appropriate services based on child's age. Design: An Early Hearing Detection and Intervention-Pediatric Audiology Links to Services expert panel was convened to create a survey to collect audiology facility information. Professional practice documents were reviewed, a survey was designed to collect pertinent test protocols of each audiology facility, and a standard of care template was created to cross-check survey answers. Audiology facility information across the United States was collected and compiled into a directory structured and displayed in an interactive website, ehdipals.org. Results: Since November 7, 2012, to May 21, 2016, over 1000 facilities have completed the survey and become listed in the Early Hearing Detection and Intervention-Pediatric Audiology Links to Services directory. The site has registered 10,759 unique visitors, 151,981 page views, and 9134 unique searches from consumers. User feedback has been positive overall. Conclusion: A searchable, web-based facility directory has proven useful to consumers as a tool to help them differentiate whether a facility was set up to test newborns versus young children. Use of a preprogrammed standard of practice template to cross-check survey answers was also shown to be a practical aid. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Consequences of Early Conductive Hearing Loss on Long-Term Binaural Processing.

Objectives: The aim of the study was to investigate the long-term effects of early conductive hearing loss on binaural processing in school-age children. Design: One hundred and eighteen children participated in the study, 82 children with a documented history of conductive hearing loss associated with otitis media and 36 controls who had documented histories showing no evidence of otitis media or conductive hearing loss. All children were demonstrated to have normal-hearing acuity and middle ear function at the time of assessment. The Listening in Spatialized Noise Sentence (LiSN-S) task and the masking level difference (MLD) task were used as the two different measures of binaural interaction ability. Results: Children with a history of conductive hearing loss performed significantly poorer than controls on all LiSN-S conditions relying on binaural cues (DV90, p =

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Mevalonate Cascade and its Regulation in Cholesterol Metabolism in Different Tissues in Health and Disease

The cholesterol biosynthesis pathway, also referred to as the mevalonate (MVA) pathway, is responsible for the biosynthesis of two key isoprenoids: farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational modification of small GTPases by FPP and GGPP has captured much attention due to their potential contribution to cancer, cardiovascular and neurodegenerative diseases. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) catalyzes the conversion of HMG-CoA to MVA, and is the rate-limiting step in the biosynthesis of cholesterol. Statins are HMGCR inhibitors that are used extensively in the treatment of hypercholesterolemia. Inhibitors of the MVA pathway exhibit anti-tumor effects and may reduce cancer incidence and cancer-related mortality in humans. </p> <p> In this review, we will focus on the mevalonate cascade and its regulation in cholesterol metabolism as well as polymorphisms of the MVA cascade in cancer development, infectious and cardiovascular disease (CVD).

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Patient Engagement in Randomized Controlled Tai Chi Clinical Trials among the Chronically Ill

Background: Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. <p></p> Aim: This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. <p></p> Methods: RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson's disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. <p></p> Results and Conclusion: We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient's life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient engagement in the intervention in order to clarify its specific role on health. <p></p>

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A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial

Background: No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. <p></p> Objectives: Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. <p></p> Methods: 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. <p></p> Result: Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. <p></p> Conclusion: Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18). <p></p>

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Snacking and Diet Quality Are Associated With the Coping Strategies Used By a Socioeconomically Diverse Urban Cohort of African-American and White Adults

Publication date: Available online 29 March 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Marie Fanelli Kuczmarski, Nancy Cotugna, Ryan T. Pohlig, May A. Beydoun, Erica L. Adams, Michele K. Evans, Alan B. Zonderman
BackgroundStress affects health-related quality of life through several pathways, including physiological processes and health behaviors. There is always a relationship between stress (the stimulus) and coping (the response). The relationship between snacking and snackers' diet quality and stress coping is a topic overlooked in research.ObjectiveThe study was primarily designed to determine whether energy provided by snacks and diet quality were associated with coping behaviors to manage stress.DesignWe analyzed a baseline cohort of the Healthy Aging in Neighborhoods of Diversity across the Life Span study (2004 to 2009).ParticipantsThe sample was composed of 2,177 socioeconomically diverse African-American and white adults who resided in Baltimore, MD.Main outcome measuresEnergy from snacks was calculated from 2 days of 24-hour dietary recalls collected using the US Department of Agriculture's Automated Multiple Pass Method. Snack occasions were self-reported as distinct eating occasions. Diet quality was evaluated by the Healthy Eating Index-2010.Statistical analyses performedMultiple regression analyses were used to determine whether coping factors were associated with either energy provided by snacks or Healthy Eating Index-2010, adjusting for age, sex, race, socioeconomic status, education, literacy, and perceived stress. Coping was measured by the Brief COPE Inventory with instrument variables categorized into three factors: problem-focused coping, emotion-focused coping, and use of support. Perceived stress was measured with the 4-item Perceived Stress Scale.ResultsAdjusting for perceived stress and selected demographic characteristics, emotion-focused coping strategies were associated with greater energy intakes from snacks (P=0.020), and use of coping strategies involving support was positively associated with better diet quality (P=0.009).ConclusionsEnergy contributed by snacks and diet quality were affected by the strategy that an individual used to cope with stress. The findings suggest that health professionals working with individuals seeking guidance to modify their eating practices should assess a person's coping strategies to manage stress.



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The Telemark Breast Score: a Valid Method for Evaluation of Outcome after Breast Surgery

imageBackground: "Telemark Breast Score" (TBS) has been developed at Telemark Hospital in Norway for evaluation of results after breast surgery based on standardized patients' photographs taken as a part of daily routine. Its reliability has recently been tested and approved. The external validity of the TBS was assessed by matching its data against the internationally recognized Breast-Q (BQ) questionnaire as a further step to study the validity of this new tool. Methods: The ideal distribution of breast volume is 45% of the total volume above and 55% below the nipple, and a 40° slope line at the upper pole. TBS makes the evaluation of these parameters of breast aesthetics more explicit. The method has been tested on photographs from 31 patients operated on for breast cancer with the Deep Inferior Perforator Flap. The evaluation was done by an independent experienced plastic surgeon earlier participating in the test–retests. The external validity of TBS was investigated against domains 1 and 3 of the BQ reconstruction module. The concordance between ratings was analyzed. Results: Concordance between TBS items and BQ domain 1 items regarding patient satisfaction, and between TBS items and BQ domain 3 items regarding how the patient experienced the outcome of breast reconstruction was relatively high except for 6 comparisons where we could not statistically ensure that more pairs were concordant than discordant. A total of 178 comparisons appeared to be concordant. This means that for all other comparisons, there was a preponderance of pairs of concordant observations, which indicates that measurements from the 2 instruments follow each other. Conclusion: The present data indicate that the TBS can be recommended as a valid tool to professionals for assessment of the outcome after breast reconstruction.

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Functional and Aesthetic Thorax Reconstruction after Desmoid Tumor Resection

imageSummary: This study describes a case report of a 31-year-old patient who presented with a left thoracic tumor on costal cartilages 5 and 6 that was diagnosed as a desmoid tumor 3 years after receiving retropectoral breast implants for cosmetic reasons. The integral reconstruction of the thoracic wall, functional and aesthetic, was planned for a single surgical period. The defect secondary to the tumor resection, which left the pericardium and lung exposed, was closed using the pectoral muscle as a "pre-expanded" flap by the breast implant, and the breast aesthetic was treated bilaterally with new implants in the retromammary position. After 12 months, the patient remained free from tumor recurrence and had a satisfactory aesthetic result.

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Tumefactive demyelination associated with developmental venous anomaly: Report of two cases

Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): Mingming Ma, James Y. Chen, Edward D. Plowey, Nancy Fischbein, Michael Iv
We present two cases of tumefactive demyelination (TD) occurring in close association with a developmental venous anomaly (DVA). Our purpose is to describe the association between demyelinating lesions and venous anomalies, as only one case of TD associated with a DVA has been published in the literature. Appropriate recognition of this "do not touch" lesion may avoid invasive and potentially harmful procedures such as biopsy or resection.



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Experimental and numerical investigation of V-bent anisotropic 304L SS sheet with spring-forward considering deformation-induced martensitic transformation

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Masoud Ahmadi, Bagher Mohammad Sadeghi, Hossein Arabi
Spring-back/forward phenomenon usually occurs during various kinds of bending tests of sheet metals. In this study, using a digital image correlation (DIC) technique coupled with uniaxial tensile test, mechanical properties of AISI 304L austenitic stainless steel were determined and the results were applied into finite element analysis (FEA) for further investigations. In order to examine various parameters affecting spring-forward in V-bending, a novel V-bending die equipped with data acquisition system was designed and used to perform V-bending tests of the AISI 304L stainless steel samples. For investigating crystallographic texture evolution in the bent sample, electron backscatter diffraction (EBSD) analysis was conducted. Furthermore, microstructural characterization, micro-hardness test and residual magnetic field measurement were utilized to investigate the transformation of austenite to α′-martensite in the bent samples. The results revealed that spring-forward angle raised by increasing sample thickness and lowering bending angle and anisotropy parameter. The fraction of transformed α′-martensite was affected by mode of deformation (stress state). An empirical model was suggested to relate residual magnetic field to volume fraction of α′-martensite for bent samples. In order to control the spring-forward efficiently, the contribution of microstructural evolution in V-bent samples was discussed.

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Characterization of moisture vapor diffusion in fine aggregate mixtures using Fickian and non-Fickian models

Publication date: 15 June 2017
Source:Materials & Design, Volume 124
Author(s): Huining Xu, Jing Zhou, Qifeng Dong, Yiqiu Tan
Moisture vapor diffusion resulting from the difference in relative humidity between air and pavement material contributes to moisture damage. Understanding moisture vapor diffusion in asphalt pavement is the first task in the analysis of moisture damage. Analysis was conducted in an automated environmental chamber with a temperature precision of ±0.5°C and relative humidity precision of ±3%. Moisture uptake profiles for fine aggregate mixtures (FAMs) under various environmental conditions (relative humidity and ambient air temperature) and constituent materials (aggregate and asphalt binder) were measured. Preliminary data analysis showed the existence of Non-Fickian diffusion behavior. Therefore, two non-Fickian and one Fickian models were introduced to fit the measured moisture uptake data and determine FAM diffusion characteristics, such as diffusion coefficient, diffused moisture phase, and time-variable diffusion. Based on the variation in FAM diffusion characteristics under various experimental conditions and constituent material combinations, sensitivity analysis was conducted with one-way ANOVA and the determinants of FAM vapor diffusion characteristics were proposed.

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The left intraparietal sulcus adapts to symbolic number in both the visual and auditory modalities: Evidence from fMRI

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Publication date: June 2017
Source:NeuroImage, Volume 153
Author(s): Stephan E. Vogel, Celia Goffin, Joshua Bohnenberger, Karl Koschutnig, Gernot Reishofer, Roland H. Grabner, Daniel Ansari
A growing body of evidence from functional Magnetic Resonance Imaging adaptation (fMRIa) has implicated the left intraparietal sulcus (IPS) as a crucial brain region representing the semantic of number symbols. However, it is currently unknown to what extent the left IPS brain activity can be generalized across modalities (e.g., Arabic digits and spoken number words) and how robust and reproducible numerical adaptation effects are.In two separate fMRIa experiments we habituated the brain response of 20 native English-speaking (Experiment 1) and 34 native German-speaking (Experiment 2) adults to Arabic digits or spoken number words. Consistent with previous findings, experiment 1 revealed numerical ratio dependent adaptation to Arabic numerals in the left IPS using both conventional and cortex-based alignment techniques. Experiment 2 revealed numerical ratio dependent signal recovery in the left IPS following adaptation to both Arabic numerals and spoken number words using both conventional and cortex-based alignment techniques. Together, these findings suggest that the left IPS is involved in symbolic number processing across modalities.



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Factor analysis linking functions for simultaneously modeling neural and behavioral data

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Publication date: June 2017
Source:NeuroImage, Volume 153
Author(s): Brandon M. Turner, Ting Wang, Edgar C. Merkle
A growing number of researchers have advocated for the advancement of cognitive neuroscience by blending cognitive models with neurophysiology. The recently proposed joint modeling framework is one way to bridge the gap between the abstractions assumed by cognitive models and the neurophysiology obtained by modern methods in neuroscience. Despite this advancement, the current method for linking the two domains is hindered by the dimensionality of the neural data. In this article, we present a new linking function based on factor analysis that allows joint models to grow linearly in complexity with increases in the number of neural features. The new linking function is then evaluated in two simulation studies. The first simulation study shows how the model parameters can be accurately recovered when there are many neural features, that mimics real-world applications. The second simulation shows how the new linking function can (1) properly recover a representation of the data generating model, even in the case of model misspecification, and (2) outperform the previous linking function in a cross-validation test. We close by applying a model equipped with the new linking function to real-world data from a perceptual decision making task. The model allows us to understand how differences in the model parameters emerge as a function of differences in brain function across speed and accuracy instruction.



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Predictive position computations mediated by parietal areas: TMS evidence

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Publication date: June 2017
Source:NeuroImage, Volume 153
Author(s): Grace Edwards, Céline Paeye, Philippe Marque, Rufin VanRullen, Patrick Cavanagh
When objects move or the eyes move, the visual system can predict the consequence and generate a percept of the target at its new position. This predictive localization may depend on eye movement control in the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and on motion analysis in the medial temporal area (MT). Across two experiments we examined whether repetitive transcranial magnetic stimulation (rTMS) over right FEF, right IPS, right MT, and a control site, peripheral V1/V2, diminished participants' perception of two cases of predictive position perception: trans-saccadic fusion, and the flash grab illusion, both presented in the contralateral visual field. In trans-saccadic fusion trials, participants saccade toward a stimulus that is replaced with another stimulus during the saccade. Frequently, predictive position mechanisms lead to a fused percept of pre- and post-saccade stimuli (Paeye et al., 2017). We found that rTMS to IPS significantly decreased the frequency of perceiving trans-saccadic fusion within the first 10min after stimulation. In the flash grab illusion, a target is flashed on a moving background leading to the percept that the target has shifted in the direction of the motion after the flash (Cavanagh and Anstis, 2013). In the first experiment, the reduction in the flash grab illusion after rTMS to IPS and FEF did not reach significance. In the second experiment, using a stronger version of the flash grab, the illusory shift did decrease significantly after rTMS to IPS although not after rTMS to FEF or to MT. These findings suggest that right IPS contributes to predictive position perception during saccades and motion processing in the contralateral visual field.



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Optical-flow analysis toolbox for characterization of spatiotemporal dynamics in mesoscale optical imaging of brain activity

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Publication date: June 2017
Source:NeuroImage, Volume 153
Author(s): Navvab Afrashteh, Samsoon Inayat, Mostafa Mohsenvand, Majid H. Mohajerani
Wide-field optical imaging techniques constitute powerful tools to investigate mesoscale neuronal activity. The sampled data constitutes a sequence of image frames in which one can investigate the flow of brain activity starting and terminating at source and sink locations respectively. Approaches to the analyses of information flow include qualitative assessment to identify sources and sinks of activity as well as their trajectories, and quantitative measurements based on computing the temporal variation of the intensity of pixels. Furthermore, in a few studies estimates of wave motion have been reported using optical-flow techniques from computer vision. However, a comprehensive toolbox for the quantitative analyses of mesoscale brain activity data is still lacking. We present a graphical-user-interface toolbox based in Matlab® for investigating the spatiotemporal dynamics of mesoscale brain activity using optical-flow analyses. The toolbox includes the implementation of three optical-flow methods namely Horn-Schunck, Combined Local-Global, and Temporospatial algorithms for estimating velocity vector fields of flow of mesoscale brain activity. From the velocity vector fields we determined the locations of sources and sinks as well as the trajectories and temporal velocities of flow of activity. Using simulated data as well as experimentally derived sensory-evoked voltage and calcium imaging data from mice, we compared the efficacy of the three optical-flow methods for determining spatiotemporal dynamics. Our results indicate that the combined local-global method we employed, yields the best results for estimating wave motion. The automated approach permits rapid and effective quantification of mesoscale brain dynamics and may facilitate the study of brain function in response to new experiences or pathology.



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Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood

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Publication date: June 2017
Source:NeuroImage, Volume 153
Author(s): Ana M. Daugherty, Robert Flinn, Noa Ofen
Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution images in a sample of healthy participants (age 8–25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus.



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SEEG dipole source localization based on an empirical Bayesian approach taking into account forward model uncertainties

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Publication date: June 2017
Source:NeuroImage, Volume 153
Author(s): S. Le Cam, R. Ranta, V. Caune, G. Korats, L. Koessler, L. Maillard, V. Louis-Dorr
Electromagnetic brain source localization consists in the inversion of a forward model based on a limited number of potential measurements. A wide range of methods has been developed to regularize this severely ill-posed problem and to reduce the solution space, imposing spatial smoothness, anatomical constraint or sparsity of the activated source map. This last criteria, based on physiological assumptions stating that in some particular events (e.g., epileptic spikes, evoked potential) few focal area of the brain are simultaneously actives, has gained more and more interest. Bayesian approaches have the ability to provide sparse solutions under adequate parametrization, and bring a convenient framework for the introduction of priors in the form of probabilistic density functions. However the quality of the forward model is rarely questioned while this parameter has undoubtedly a great influence on the solution. Its construction suffers from numerous approximation and uncertainties, even when using realistic numerical models. In addition, it often encodes a coarse sampling of the continuous solution space due to the computational burden its inversion implies. In this work we propose an empirical Bayesian approach to take into account the uncertainties of the forward model by allowing constrained variations around a prior physical model, in the particular context of SEEG measurements. We demonstrate on simulations that the method enhance the accuracy of the source time-course estimation as well as the sparsity of the resulting source map. Results on real signals prove the applicability of the method in real contexts.



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Technical Feasibility of Acoustic Coordinated Reset Therapy for Tinnitus Delivered via Hearing Aids: A Case Study

Primary tinnitus has a severe negative influence on the quality of life of a substantial portion of the general population. When acoustic coordinated reset (CR) neuromodulation stimuli are delivered for several hours per day over several weeks a clinically significant symptom reduction in patients with primary tonal tinnitus has been reported by several clinical sites. Here, we reported the first case where CR neuromodulation was delivered through a hearing aid. A 52-year-old man with chronic primary tonal tinnitus was previously considered untreatable with sound therapy. He initially received the classic CR treatment protocol with signals delivered with the separate proprietary device with his hearing aids removed during treatment. He was subsequently treated with the therapy being deployed through a set of contemporary hearing aids. After 5 months of classic CR treatment with the separate custom device, the THI and VASL/A scores worsened by 57% and 13%/14%, respectively. Using the hearing aid without CR treatment for 5 months no change in tinnitus symptoms was observed. However, after three months of CR treatment delivered through the hearing aids, the THI and VASL/A scores were reduced by 70% and 32%/32%, respectively.

http://ift.tt/2oj78Jg

Technical Feasibility of Acoustic Coordinated Reset Therapy for Tinnitus Delivered via Hearing Aids: A Case Study

Primary tinnitus has a severe negative influence on the quality of life of a substantial portion of the general population. When acoustic coordinated reset (CR) neuromodulation stimuli are delivered for several hours per day over several weeks a clinically significant symptom reduction in patients with primary tonal tinnitus has been reported by several clinical sites. Here, we reported the first case where CR neuromodulation was delivered through a hearing aid. A 52-year-old man with chronic primary tonal tinnitus was previously considered untreatable with sound therapy. He initially received the classic CR treatment protocol with signals delivered with the separate proprietary device with his hearing aids removed during treatment. He was subsequently treated with the therapy being deployed through a set of contemporary hearing aids. After 5 months of classic CR treatment with the separate custom device, the THI and VASL/A scores worsened by 57% and 13%/14%, respectively. Using the hearing aid without CR treatment for 5 months no change in tinnitus symptoms was observed. However, after three months of CR treatment delivered through the hearing aids, the THI and VASL/A scores were reduced by 70% and 32%/32%, respectively.

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The Effect of Soft Tissue Infections on Device Performance in Adult Cochlear Implant Recipients.

Objective: The aim of this study was to examine the effect of cochlear implant (CI) site infection and its subsequent management on CI mapping and CI performance. Risk factors for CI infections and pathogens causing infections were reviewed. Treatment options for CI infections were examined. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Adult patients with a significant CI soft tissue infection from the Northern Cochlear Implant Programme, New Zealand over a 10-year period (August 2004 until August 2014). Intervention: Patients were treated with intravenous antibiotics, washout and debridement or ex-plantation and reimplantation of CI. Main Outcome Measure: CI mapping results and implant performance before and after management of CI infections were compared. Results: There were nine CI infections. Most patients (7/9) were treated with washout and debridement. One patient required removal of the CI and one patient was deemed medically unfit for a general anaesthetic and was managed conservatively with antibiotics alone. Seven patients received long-term antibiotics. Four patients were able to maintain CI performance after salvage treatment of the CI infection. Three patients had poorer CI performance after salvage treatment. One patient had reimplantation and became a nonuser due to only partial reinsertion. Conclusion: The pathophysiology of CI infections is complex. Infections can occur many years after CI surgery. The most common bacteria identified were Staphylococcus aureus, Pseudomonas aeruginosa, and skin commensals. Biofilms are present around implants that are removed from patients and biofilms may play a role in CI infections, but the mechanism of infection is not clear. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Hearing Preservation Outcomes for 139 Cochlear Implant Recipients Using a Thin Straight Electrode Array.

Objective: To assess the hearing preservation outcomes in a large group of adult cochlear implant recipients implanted with a thin straight electrode array using atraumatic surgical techniques. Factors affecting hearing preservation will be investigated. Study Design: Prospective cohort study undertaken at the Royal Victorian Eye and Ear Hospital in Melbourne, Australia from December 2010 to May 2015. Setting: Tertiary academic hospital. Patients: One hundred thirty-nine adults undergoing cochlear implantation (CI). Main Outcome Measure: Primary outcome measure of interest was pre and postoperative pure-tone audiometry. Results: Median low-frequency hearing change for the whole group of 139 recipients was -22.5 dB at the 3 months postop point. Eighty-six participants had functional preoperative low-frequency hearing (

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Preoperative CT Assessment in CI: Dehiscence of the Labyrinthine Segment of the Facial Nerve Causing Facial Nerve Stimulation.

No abstract available

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Cochlear Implants Versus Hearing Aids in a Middle-Income Country: Costs, Productivity, and Quality of Life.

Objective: In Colombia there are three main treatment approaches for bilateral profound sensorineural hearing loss, also known as profound deafness (PD): cochlear implants (CI), hearing aids (HA), and no treatment (NT). The objective of this study is to determine the optimal treatment approach for PD in terms of productivity and cost-effectiveness. Study Design: Hearing levels and SES data were obtained from audiometric tests conducted on 100 patients with CI. For each treatment approach, productivity and cost-effectiveness assessments were estimated using influence diagrams and Monte Carlo simulations. Productivity was calculated as the net present value of a patient's lifetime income divided by total health-related and educational costs. For the CI and HA, the cost-effectiveness indicator was calculated as quality-adjusted life-years (QALYs) gained in comparison with the NT approach divided by the total cost of the treatment option. Results: The results for the CI, the HA, and NT in terms of productivity ratio were 1.53, 0.94, and 1.47, respectively. Patients using CI had a gain of 5.7 QALYs, whereas patients using HA had a gain of 4.6 QALYs. The results for the CI and the HA in terms of cost-effectiveness were $15,169 and $15,430 per QALY, respectively. Conclusion: The CI was found to be the optimal treatment for PD, as it was the most efficient and cost-effective in terms of improving patients' productivity and quality of life. We observed that children who had received CI developed hearing and speech abilities that contributed to their productivity and quality of life to a greater extent than those with HA. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Electrode Array Displacement into the Fallopian Canal in Revisions of Long-standing Cochlear Implants.

Objective: To describe extracochlear extension of revision cochlear implant arrays into the Fallopian canal. Patients: Two adult patients with extension of revision cochlear implant arrays into the Fallopian canal. Interventions: Computed tomography (CT), selective deactivation of non-functional electrodes. Main Outcome Measures: Facial nerve function, facial nerve stimulation, cochlear implant electrode position, radiography, functional hearing. Results: Two patients presented with failure of their long-standing cochlear implants (CIs). One patient with presumed postviral hearing loss presented with declining function and increasing facial stimulation from an implant placed 30 years previous. A second with postmeningitic hearing loss presented with a draining mastoid fistula from an implant placed 7 years before. Both patients were reimplanted with minimal insertion resistance via the established electrode tract, yet demonstrated facial nerve stimulation during intraoperative telemetry and on device activation. Postoperative CTs of each patient showed exit of the electrode from the cochlea into the tympanic or labyrinthine Fallopian canal. Both patients can use their devices effectively with selective electrode deactivation. Conclusions: Our cases illustrate the potential association of long-standing electrodes with otic capsule changes, allowing extracochlear malposition of subsequent arrays. This can occur despite apparently uneventful reinsertion of a flexible array without undue force. Previously reported histopathology confirms the potential for a reactive osteitis from arrays that may contribute to this phenomenon. Intraoperative facial stimulation with neural telemetry testing can raise suspicion of a malpositioned array involving the Fallopian canal. Such cases can be effectively managed with selective deactivation of malpositioned electrode contacts. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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“Are We in Sync with Each Other?” Exploring the Effects of Cosleeping on Heterosexual Couples’ Sleep Using Simultaneous Polysomnography: A Pilot Study

The present study aimed to explore dynamic and interactive aspects of cosleep in heterosexual couples. The sample consisted of eight young healthy adults who belonged to four heterosexual couples with a good relationship quality and a history of cosleeping. All individuals underwent simultaneous polysomnography in a sleep laboratory for four nights in which they slept individually and with their partner. Also, a sleep protocol of subjective sleep measures was completed. Statistical analyses included cross recurrence quantification analysis to assess synchronization during sleep. Cosleeping was associated with better subjective sleep quality, increased total sleep time, sleep efficiency, total slow wave sleep, and REM sleep. Sleep stages were more synchronized during cosleep independent of awakenings. Cardiorespiratory measures remained unchanged. The results indicate that young healthy couples in good relationships benefit from cosleeping on a subjective and objective level. Combining simultaneous polysomnography and cross recurrence quantification analysis is a promising method to study dynamic and interactive aspects of cosleep possibly leading to deeper understanding of the role of sleep for sociality, the nature of REM sleep, and the partner as a social zeitgeber. Moreover, clinical implications may arise from these findings.

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A simple post-synthesis conversion approach to Zn(OH)F and the effects of fluorine and hydroxyl on the photodegradation properties of dye wastewater

Publication date: 5 July 2017
Source:Journal of Hazardous Materials, Volume 333
Author(s): Hao Yang, Fei Teng, Wenhao Gu, Zailun Liu, Yunxuan Zhao, An Zhang, Zhe Liu, Yiran Teng
In this work, Zn(OH)F is prepared by an initiative, simple post-synthesis method, in which the molar ratio of F/Zn (RF) was varied to investigate the effect of the NH4F amounts added on the samples. Further, we have mainly investigated their energy bands and photochemical properties. Under UV light irradiation (λ£420nm), the samples (RF=0,1,2) show the high degradation activities of methylene blue (MB) dye, namely, 80% of MB can be degraded after 8min. It is found that the hydroxyl and fluorine have greatly down shifted the conduction band (CB, 0.99eV) and valence band (VB, 4.17eV) of Zn(OH)F, compared with ZnO (CB=−0.31eV, VB=2.89eV), but with the nearly same band gap. For the degradation of MB dye, the main oxidative species are holes and hydroxyl radicals for ZnO and Zn(OH)F, respectively. This study suggests that this simple post-synthesis fluorination approach could be extended to develop the other photocatalysts; moreover, we can facilely tune the band structure and photocatalytic activity by introducing or removing hydroxyl and fluorine, which could benefit to develop new photocatalysts.

Graphical abstract

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Oxygen accumulation on metal surfaces investigated by XPS, AES and LEIS, an issue for sputter depth profiling under UHV conditions

Publication date: 31 July 2017
Source:Applied Surface Science, Volume 411
Author(s): R. Steinberger, C.E. Celedón, B. Bruckner, D. Roth, J. Duchoslav, M. Arndt, P. Kürnsteiner, T. Steck, J. Faderl, C.K. Riener, G. Angeli, P. Bauer, D. Stifter
Depth profiling using surface sensitive analysis methods in combination with sputter ion etching is a common procedure for thorough material investigations, where clean surfaces free of any contamination are essential. Hence, surface analytic studies are mostly performed under ultra-high vacuum (UHV) conditions, but the cleanness of such UHV environments is usually overrated. Consequently, the current study highlights the in principle known impact of the residual gas on metal surfaces (Fe, Mg, Al, Cr and Zn) for various surface analytics methods, like X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES) and low-energy ion scattering (LEIS). The investigations with modern, state-of-the-art equipment showed different behaviors for the metal surfaces in UHV during acquisition: (i) no impact for Zn, even after long time, (ii) solely adsorption of oxygen for Fe, slight and slow changes for Cr and (iii) adsorption accompanied by oxide formation for Al and Mg. The efficiency of different counter measures was tested and the acquired knowledge was finally used for ZnMgAl coated steel to obtain accurate depth profiles, which exhibited before serious artifacts when data acquisition was performed in an inconsiderate way.

Graphical abstract

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Emetine induces estrogen receptor alpha degradation and prevents 17β-estradiol-induced breast cancer cell proliferation



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Checkpointhemmer beim Melanom: Nebenwirkungen meist geringgradig

Wie stark fallen Nebenwirkungen im Zusammenhang mit der Immuntherapie bei Melanompatienten aus und wie lassen sie sich beherrschen? Antworten auf diese Fragen lassen sich an der gepoolten Auswertung von vier klinischen Studien ablesen.



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Madelung-Krankheit: Überzogen von Fetteinlagerungen



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Niedrig-Risiko-Basalzellkarzinome: zuerst ein Therapieversuch mit Imiquimod?

In der Behandlung von Basalzellkarzinomen schneidet Imiquimod zwar schlechter ab als die Exzision. Bei frühem Ansprechen scheint der Erfolg aber langfristig Bestand zu haben.



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Ist Ihr Wartebereich noch zeitgemäß?

Als Arzt fachlich immer auf dem neuesten Stand zu sein, ist für Sie wahrscheinlich selbstverständlich. Ob sich Ihre Patienten jedoch bei Ihnen wohlfühlen, gern wiederkommen oder gar Empfehlungen aussprechen, entscheidet sich meist weitaus früher als bei der eigentlichen Behandlung: im Wartebereich.



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GOÄ-Mindestzeiten müssen nicht immer auf die Rechnung

Gehören Zeitvorgaben aus der Gebührenordnung für Ärzte (GOÄ) mit auf die Rechnung? Wann könnte es Ärger mit Patienten oder mit der Krankenversicherung geben, wenn die Angabe der Mindestzeit fehlt? Die Antwort steht, wie so oft, im Kleingedruckten der GOÄ.



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Dieses Geschwür ist alles andere als banal



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Neuer Ansatz gegen Akne

Ein topischer Hemmstoff der Sebumproduktion hat sich in einer Phase-IIa-Studie bei Acne vulgaris im Gesicht bewährt.



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„Die Forderung nach evidenzbasierter Medizin wird aufgeweicht“



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Kombinationstherapie beim mukosalen Melanom

In einer gepoolten Datenanalyse wurde erstmals Sicherheit und Wirksamkeit von Nivolumab als Monosubstanz und in Kombination mit Ipilimumab beim seltenen, hochaggressiven mukosalen Melanom untersucht.



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Melanom: breites Spektrum an Nebenwirkungen

Anti-PD-1-Antikörper sind eine effektive Therapieoption bei metastasiertem Melanom und anderen Krebsarten. Allerdings können sie immunbedingte unerwünschte Ereignisse induzieren.



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Vitiligo: Tacrolimus unterstützt UV-Therapie bei Kindern

Bei Kindern mit Vitiligo wird eine UV-Bestrahlung in der Regel bei großflächigen Pigmentierungsstörungen angewandt, Tacrolimussalbe bei kleineren Flecken. Über die Wirksamkeit einer Kombitherapie bei Kindern war bislang wenig bekannt. Diese Lücke wollten indische Hautärzte mit einer eigenen kleinen Studie füllen.



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So viel verdienen niedergelassene Ärzte

Trotz steigender Betriebskosten: Die wirtschaftliche Lage in den Vertragsarztpraxen hat sich zwischen den Jahren 2011 und 2014 merklich verbessert. Die Einnahmen je Inhaber stiegen um 10,2 %, der Jahresüberschuss — also der Gewinn — um 6,7 %, während die Praxiskosten um 8,9 % zulegten. Das zeigen die aktuellen Daten des Zi-Praxis-Panels (ZiPP), die aus über 5.000 Praxen generiert wurden.



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Die Angst vor dem Altern

Narziss wird für Hochmut und Eigenliebe mit dem Tod bestraft, bevor er mit dem Alter konfrontiert werden kann. Sein Seelenverwandter aus dem 19. Jahrhundert hat Jahrzehnte, sein unverändert jugendliches Aussehen auszukosten — was seinen Hochmut erst auf die Spitze treibt. Doch mit dem inbrünstigen Wunsch, nicht zu altern, hat Dorian Gray bereits eine verheerende Wahl getroffen.



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Inhaltsverzeichnis



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Zahl der dokumentierten Melanome nimmt zu

Um die Stadienverteilung von Melanomen und die Überlebensraten der Patienten zu analysieren, hatte die Arbeitsgemeinschaft Deutscher Tumorzentren (ADT) die deutschen populationsbasierten und klinischen Tumorregister um Daten zu den zwischen 2002 und 2011 neu diagnostizierten Melanomen gebeten. Nun liegt die Auswertung von 61.895 Fällen vor.



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Vorsicht bei der Selbstbehandlung von Schwielen und Clavi!

Bevor sich Patienten mit Schwielen und Hühneraugen einfach besser passende Schuhe kaufen, behandeln sie sich lieber selbst etwa mit Hühneraugenpflastern, Credohobeln oder sogar Bohrmaschinen. Dies birgt diverse Gefahren. Von welchen Maßnahmen sollten Sie abraten?



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IL-17A-Antikörper bei palmoplantarer Psoriasis

Psoriasisbedingte Hautveränderungen an Händen und Füßen können jedes Zugreifen und jeden Schritt zur Tortur werden lassen. An diesen Stellen ist der Schuppenflechte allerdings nur schwer beizukommen. Laut einer aktuellen Phase-III-Studie verspricht der humane Antikörper Secukinumab Linderung.



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Das bringen die neuen EBM-Positionen zur Videosprechstunde

Eine Technikpauschale, die außerhalb der Gesamtvergütung läuft, und eine Video-Kontakt-Ziffer: Die neuen Leistungen im EBM für die Videosprechstunde klingen vielversprechend. Am Fernbehandlungsverbot rütteln sie aber nicht.



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Ein 30 Jahre alter Begleiter an der Brust



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Studiendesigns im Umbruch

Sie heißen CUSTOM, BATTLE oder ALCHEMIST und stehen für eine neue Generation klinischer Studien, die sich von den klassischen Protokollen deutlich unterscheiden — etwa Enrichment-, Umbrella- oder Basket-Designs. Eingeläutet hat diese Entwicklung die genetische Sequenzierung von Tumorgewebe.



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Reversible Inferolateral ST-Segment Elevation Associated with Small Bowel Obstruction

ST-segment elevation is an important and alarming electrocardiographic sign that necessitates immediate attention but does not always indicate that the primary pathology is cardiac in origin. It needs to be interpreted in the clinical context as several pathological conditions involving especially gastrointestinal tract may lead to delayed diagnosis and treatment as well as complications from invasive unnecessary interventions. We present two patients, a 64-year-old male and a 71-year-old female, who were admitted to the emergency room of a community-based hospital with similar complaints of worsening epigastric abdominal pain and were diagnosed later with small bowel obstruction. Both patients reported a history of abdominal surgeries in the past. Also in both patients the ECG showed signs of ST-segment elevation in inferior and lateral leads. These ECG changes were related to the intra-abdominal pathology as no evidence of contributing coronary artery disease could be found. In addition, prompt resolution of ST-segment elevation was seen after surgical treatment. The pathophysiological etiology of electrocardiographic changes accompanying small bowel obstruction is yet to be explored.

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Exposure to endocrine disruptors during adulthood: consequences for female fertility

Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.



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phospho-ERK and sex steroids in the mPOA: involvement in male mouse sexual behavior

This paper aimed to investigate the mechanisms triggering ERK phosphorylation and its functional role in male sexual behaviour. ERK1/2 phosphorylated form was detected in the medial preoptic area of the hypothalamus (mPOA) during the sexual stimulation of naive and sexually experienced males who were sacrificed 5 minutes after the first intromission. This mating-induced ERK phosphorylation was increased in sexually experienced males compared to naive mice. The functional role of the ERK1/2 pathway activation during sexual behaviour was explored with the administration of a MEK inhibitor, SL-327 (30 mg/kg, i.p.) 45 minutes before the contact with a receptive female. Inhibition of ERK phosphorylation was found to decrease sexual motivation in both naive and experienced males without altering their copulatory ability. The mechanisms potentially involved in this rapid ERK1/2 pathway activation were specified ex vivo on hypothalamic slices. A thirty-minute incubation with 100 nM of Testosterone (T), dihydrotestosterone (DHT) or estradiol (E2) led to ERK phosphorylation. No changes were observed following incubation with testosterone 3-(O-carboxymethyl)oxime-BSA (T-BSA), an impermeable to the plasma membrane form of testosterone. All these results indicate that ERK phosphorylation within the mPOA could be a key player in the motivational signalling pathway and considered as an index of sexual motivation. They also demonstrate the involvement of oestrogen receptor (ER) and androgen receptor (AR) transduction pathways in steroid-dependent ERK activation.



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Regulation of Brn3b by Dlx1 and Dlx2 is required for retinal ganglion cell differentiation in the vertebrate retina [RESEARCH ARTICLE]

Qi Zhang, Jamie Zagozewski, Shaohong Cheng, Rajiv Dixit, Shunzhen Zhang, Jimmy de Melo, Xiuqian Mu, William H. Klein, Nadean L. Brown, Jeffrey T. Wigle, Carol Schuurmans, and David D. Eisenstat

Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix loop helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We hypothesized that Dlx1/Dlx2 and Brn3b homeobox genes function in parallel intrinsic pathways to determine RGC fate and generated Dlx1/Dlx2/Brn3b triple knockout mice. A more severe retinal phenotype was found in the Dlx1/Dlx2/Brn3b null retinas than predicted by combining features of the Brn3b single and Dlx1/Dlx2 double knockout retinas, including near total RGC loss with a marked increase in amacrine cells in the ganglion cell layer. Furthermore, we discovered that DLX1 and DLX2 function as direct transcriptional activators of Brn3b expression. Knockdown of Dlx2 expression in primary embryonic retinal cultures and Dlx2 gain-of-function in utero strongly support that DLX2 is both necessary and sufficient for Brn3b expression in vivo. We suggest that Atoh7 specifies RGC committed progenitors and that Dlx1/Dlx2 functions both downstream of Atoh7 and in parallel but cooperative pathways involving regulation of Brn3b expression to determine RGC fate.



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Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy

Summary

Background

Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur.

Objective

We hypothesised that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives.

Methods

We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitisation with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea.

Results

Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25hi regulatory T cells among CD4+ T cells in the mesenteric lymph nodes.

Conclusions and Clinical Relevance

A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies.

This article is protected by copyright. All rights reserved.



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Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy

Summary

Background

Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur.

Objective

We hypothesised that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives.

Methods

We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitisation with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea.

Results

Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25hi regulatory T cells among CD4+ T cells in the mesenteric lymph nodes.

Conclusions and Clinical Relevance

A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies.

This article is protected by copyright. All rights reserved.



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Treatment Options for Metastatic Colorectal Cancer in Patients with Liver Dysfunction due to Malignancy

Publication date: Available online 29 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): L. Faugeras, A. Dili, A. Druez, B. Krug, Decoster, L. D'Hondt
BackgroundThe survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism.Material and methodsWe have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible.ResultsSome drugs appear to be feasible options for patients with hepatic insufficiency. Agents such as 5-fluorouracil and oxaliplatin, as well as monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab, can potentially be used in these cases. On the other hand, irinotecan and regorafenib cannot be recommended because of the risk of increased toxicity.ConclusionTreatment of patients with colorectal cancer and liver dysfunction represents a major challenge because the prognosis is usually very poor and alteration of liver function is normally an exclusion criterion in clinical trials. In this review, we present evidence regarding the use of each drug in patients with colorectal cancer and hepatic impairment.



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Refractory burning mouth syndrome: clinical and paraclinical evaluation, comorbiities, treatment and outcome

Burning Mouth Syndrome (BMS) is a chronic pain condition characterized by persistent intraoral burning without related objective findings and unknown etiology that affects elderly females mostly. There is no s...

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Lower inhibitory control interacts with greater pain catastrophizing to predict greater pain intensity in women with migraine and overweight/obesity

Pain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to supp...

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Morbidity of the Free Fibula Flap Reconstruction in Head and Neck Malignancies

J reconstr Microsurg
DOI: 10.1055/s-0037-1601402



Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001, USA

Article in Thieme eJournals:
Table of contents  |  Full text



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Diffusion Tensor Imaging Tractography and MRI Perfusion in Post Traumatic Brain Injury Hypersomnia

Three years ago, a 48-year-old female patient had head trauma with commotion followed by a four-month coma. After hospital discharge, she complained of bilateral frontal headache, amnesia related to the episode and excessive daytime sleepiness with prolonged non-restorative naps any time of day. Previous patient history did not report neurological or psychiatric illness. At our first outpatient sleep service (besides a normal neurological exam), she did report severe sleep disturbances, particularly an incoercible daytime sleepiness followed by non-refreshing and prolonged naps (Epworth Scale 18), prolonged night-time sleep with snoring and an important morning sleep inertia.

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Can floseal™ be applied safely during otologic surgery? Assessment of ototoxicity in a chinchilla animal model

In otologic surgery good visualization is paramount, and patients with bleeding diatheses or who need to be anti-coagulated can present a significant challenge. Here, we determine whether Floseal™, a hemostati...

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Can floseal™ be applied safely during otologic surgery? Assessment of ototoxicity in a chinchilla animal model

In otologic surgery good visualization is paramount, and patients with bleeding diatheses or who need to be anti-coagulated can present a significant challenge. Here, we determine whether Floseal™, a hemostati...

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Evaluation of the postoperative cognitive dysfunction in elderly patients with general anesthesia

OBJECTIVE: The present study is aimed to study the neuron-specific enolase (NSE) and S100b proteins in the evaluation of postoperative cognitive dysfunction in elderly patients with general anesthesia.

PATIENTS AND METHODS: A total of 142 aged patients, who were treated with transurethral resection of the prostate (TURP) surgery under general anesthesia with propofol from June 2014 to December 2015, were randomly divided into two groups. The experiment group was given scopolamine butylbromide by intramuscular injection before the operation, while the control group had no preoperative intramuscular injection. The propofol was used for maintenance during the operation. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were adopted for testing the patients on preoperative day 1, postoperative day 2 and postoperative day 9. After the surgery, there were 4 cases of postoperative cognitive dysfunction (POCD) patients in experiment group, while 21 cases of POCD patients in control group. While the 142 healthy adult volunteers, who were admitted to physical examination center of our hospital in the corresponding period, were selected as healthy controls. The expression levels of S100b and NSE of patients, as well as healthy controls, were detected by ELISA.

RESULTS: In POCD patients, serum S100b and NSE levels were evidently higher than those of patients without POCD and healthy control group (p < 0.05). S100b and NSE levels of POCD patients in experiment group were significantly lower than those of control group (p < 0.05). Serum S100b and NSE levels are higher, the longer duration of POCD is, as the correlation coefficient rs = -0.1342, -1.6644, p < 0.05.

CONCLUSIONS: The expression levels of S100b protein and plasma NSE in the serum of POCD patients increased, which indicated the severity of the disease. The preoperative intramuscular injection of scopolamine butylbromide has important clinical significance for the prevention of POCD.

L'articolo Evaluation of the postoperative cognitive dysfunction in elderly patients with general anesthesia sembra essere il primo su European Review.



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Anesthesia and analgesia in breast surgery: the benefits of peripheral nerve block

Breast surgery is frequently associated with postoperative pain, nausea and vomiting, that result in increased patient's suffering, prolongation of hospital stays and related costs. Thoracic paravertebral nerve block (TPVB) is a viable option to the classic multimodal analgesia in breast surgery as it enhances surgical anesthesia and postoperative analgesia.

In this review, we report the results of a number of studies on the role of TPVB in breast surgery. This technique is associated with a superior control of the pain, a reduction in opioids consumption after surgery, a decrease in postoperative nausea and vomiting, and an overall decrease in length of hospital stay. In particular, TPVB seems to provide the most benefits in patients undergoing an unilateral or bilateral mastectomy followed by immediate reconstruction. Some studies also suggest that the use of regional anesthesia-analgesia could attenuate perioperative immunosuppression and minimize metastases in breast cancer patients.

TPVB can be also coupled with other regional anesthetic techniques such as pectoral nerve block (PNB), thus increasing the reduction in postsurgical pain, opioids consumption and length of hospital stays.

L'articolo Anesthesia and analgesia in breast surgery: the benefits of peripheral nerve block sembra essere il primo su European Review.



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Racial disparities in the impact of chronic pruritus: A cross-sectional study on quality of life and resource utilization in United States Veterans

Chronic pruritus has a lifetime prevalence of up to 26% in the worldwide population. Research has shown that the incidence and quality of life (QoL) impact of chronic pruritus varies by race.

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Tumor recurrence of keratinocyte carcinomas judged appropriate for Mohs micrographic surgery using Appropriate Use Criteria

The use of Mohs micrographic surgery (MMS) has increased greatly to treat basal cell and cutaneous squamous cell carcinomas (keratinocyte carcinoma [KC]), and consensus-based Appropriate Use Criteria (AUC) were developed to identify tumors for which MMS is appropriate.

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Association of atopy phenotypes with new development of asthma and bronchial hyperresponsiveness in school-aged children

Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood.

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Association of atopy phenotypes with new development of asthma and bronchial hyperresponsiveness in school-aged children

Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood.

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Editorial board

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Publication date: June 2017
Source:Biomaterials, Volume 128





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Helmet Wear and Craniofacial Trauma Burden: A Plea for Regulations Mandating Protective Helmet Wear

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0037-1601430

Helmet wear offers protection in various ways against craniomaxillofacial and brain trauma. The specific pattern and overall burden of craniofacial trauma among helmeted and unhelmeted patients has not been well defined.This is a retrospective review of trauma patients involved in documented helmet-associated injuries that presented to the Mayo Clinic Emergency Department in Rochester, Minnesota, and completed initial trauma evaluation between 1999 and 2015.A total of 417 patients (50% unhelmeted, 82% male) were identified. The median age at injury was 22.9 years (interquartile range [IQR]: 15.2–44.2]) and median follow-up was 26 months ([IQR: 2.2–64.8]). The majority of injuries involved motorcycle accidents (57.6%), bicycles (30.2%), and other modes of injury (12.7%). The mean Glasgow Coma Score (GSC) at the time of presentation was 14.2 (SD ± 2.4) and mean injury severity score (ISS) was 10.2 (SD ± 7.5). Motorcycle accidents had a higher mean ISS compared with other modes of injury (p = 0.048). Unhelmeted patients were more likely to sustain scalp lacerations (p < 0.0001), facial bone fractures (p = 0.01), scalp hematomas (p = 0.041), skull fractures (p = 0.017), and are more likely to require hospital admission (p = 0.0003). Unhelmeted patients' hospital length of stay was on average 2 days longer than helmeted patients' stay (p = 0.0721). Unhelmeted patients were more likely to require out-of-home placement than helmeted patients.Among trauma patients, helmet use was associated with less scalp lacerations and hematomas, facial bones fractures, skull fractures, and need for hospital admission. Adoption of legislation and regulations mandating protective helmet use in all states are strongly encouraged to minimize the burden of craniofacial injuries among unhelmeted patients.
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Treatment of Mandibular Angle Fractures with Single Three-Dimensional Locking Miniplates without Maxillomandibular Fixation: How Much Fixation Is Required?

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0037-1600904

The aim of this simple nonrandomized and observational study was to evaluate the efficacy of single three-dimensional (3D) plate for the treatment of mandibular angle fractures without maxillomandibular fixation.A total of 30 patients with noncomminuted fractures of mandibular angle requiring open reduction and internal fixation were included in the study. All the patients were treated by open reduction and internal fixation using single 3D titanium locking miniplate placed with the help of transbuccal trocar or Synthes 90-degree hand piece and screw driver. 3D locking titanium miniplates used in our study was four-holed, box-shaped plate, and screws with 2 mm diameter and 8 mm length. The following clinical parameters were assessed for each patient at each follow-up visit: pain (visual analog scale: 0–5), swelling (visual analog scale: 0–5), mouth opening, infection, paresthesia, hardware failure (plate fracture), occlusal discrepancies, and mobility between fracture fragments.A significant decrease in pain level was seen during the follow-up visits. No statistically significant changes were seen in swelling, but mouth opening increased in the subsequent visits. Also better results were seen in terms of fracture stability and occlusion in the postoperative period. Two cases of infection and two cases of hardware failure were noted in sixth postoperative week.3D plating system is an easy to use alternative to conventional miniplates to treat mandibular angle fractures that uses lesser foreign material, thus reducing the operative time and overall cost of the treatment. Better fracture stability and occlusion was also achieved using the 3D plating system.
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Fracture of the Clavicle following Radical Neck Dissection and Reconstruction Using Pectoralis Major Myocutaneous Flap Accompanied by Postoperative Radiotherapy

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0037-1600903

Fracture of the clavicle following radical neck dissection (RND) and/or radiotherapy is a rare complication. Several causes of fracture of the clavicle after treatment of head and neck cancer were postulated in previous reports. We present a case of fracture of the clavicle after treatment of squamous cell carcinoma of the tongue. An 81-year-old Japanese woman underwent RND, subtotal glossectomy, reconstruction using a pectoralis major myocutaneous flap (PMMCF), and postoperative radiotherapy (50.4 Gy). One month after the primary treatment, fracture of the clavicle occurred. It was thought that muscular dynamic factor and reduction of blood supply in the clavicle associated with RND and PMMCF were the causes of the fracture. We have to recognize the occurrence of this complication and try to reduce the factors related to the complication.
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Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA

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Sinus Grafts: Science and Techniques—Then and Now

Abstract

Introduction

Sinus lifts have been around for more than four decades now, and the amount of changes that we have seen in techniques and armamentarium coupled with the advent of newer materials is worth taking note of.

Materials and Methods

A complete review of the literature was done since the advent of ways and means to augment the posterior maxilla with a run through of various advantages and disadvantages of the same.

Conclusion

In conclusion, we can say that this procedure is today very predictable and offers clinicians a possibility to rehabilitate the posterior maxilla with implant-based solutions.



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Microcarrier culture enhances osteogenic potential of human periodontal ligament stromal cells

Regeneration of periodontal tissue represents a major challenge to modern tissue engineering, since cell-based therapies require large amounts of periodontal ligament stromal cells (PLSC), which can be obtained only by in vitro expansion. Ideally, the period of the in vitro expansion should be optimized for the generation of large enough numbers of pre-specified progenitor cells ready to contribute to the restoration of periodontal tissues.In the present study, we used a commercially available, three-dimensional culturing platform and alginate microcarrier cell culture system for the propagation of human PLSCs, which were derived using the explant outgrowth method.

http://ift.tt/2oAlWT5

Some Innovative Evolutions in Surgery of the Cranio-Maxillofacial Skeleton

The following remarks were presented on a lecture at the general meeting of the AAOMFS in October 2015 in Washington DC. As the first invitation to the American Association was in 1966 by its President General Bob Shira, this was my last talk in the United States at the age of 95 years.

http://ift.tt/2oAcwH1

Surgical correction of mandibular hypoplasia in hemifacial microsomia, a retrospective study in 39 patients

Repair of the mandibular deformity in hemifacial microsomia (HFM) remains controversial, and there is scant information in the literature regarding the late outcomes. The aim of this study was to evaluate architectural and aesthetic long-term outcomes for primary mandibular surgery in patients with HFM.

http://ift.tt/2nNrmwR

Cognitive deficits in obstructive sleep apnea: insights from a meta-review and comparison with deficits observed in COPD, insomnia, and sleep deprivation

Obstructive sleep apnea (OSA) is a nocturnal breathing disorder that is associated with cognitive impairment. The primary determinants of cognitive deficits in OSA are thought to be sleep disruption and blood gas abnormalities. Cognitive impairment is also seen in other disorders that are characterised primarily by sleep disturbance (e.g., sleep restriction/deprivation, insomnia) or hypoxia/hypercarbia (e.g. chronic obstructive pulmonary disease (COPD). Assessment of the cognitive defects observed in these other disorders could help better define the mechanisms underlying cognitive deficits in OSA.

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The indication for endoscopic butterfly cartilage myringoplasty in children

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Publication date: Available online 28 March 2017
Source:Auris Nasus Larynx
Author(s): Zheng-Cai Lou




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Transcanal endoscopic approach to lesions of the suprageniculate ganglion fossa

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Publication date: Available online 29 March 2017
Source:Auris Nasus Larynx
Author(s): Daniele Marchioni, Alessia Rubini, João Flávio Nogueira, Brandon Isaacson, Livio Presutti
ObjectiveThe aim of this paper would be to describe the first case series of exclusive transcanal endoscopic approach to treat lesions with limited extension at the suprageniculate fossa. This endoscopic approach allowed a complete removal of suprageniculate disesases with low complication rates using a minimally invasive surgical route.MethodsThis is a retrospective chart analysis and a surgery video recording review of these patients were performed in August 2015. From November 2011 to November 2015, 29 patients were submitted to an endoscopic transcanal lateral skull base surgery. From those 29 subjects, in 6 patients an exclusive endoscopic transcanal suprageniculate approach was performed to remove lesions located into the geniculate fossa. Surgical indications, pre-operative assessment, results were collected and the surgical technique were described.ResultsThe final study group was composed of 6 patients. 3 male and 3 female; median age is 25.3 years old. In all 6 subjects it was possible to remove the lesions using an exclusive endoscopic transcanal suprageniculate approach. No intraoperaoperative complications were observed in any patients. The mean follow up period was 15.16 months.ConclusionExclusive endoscopic transcanal suprageniculate approach is definitely a minimally invasive technique and should be consider an optimal solution to treat lesions located in the suprageniculate fossa in some patients. We introduce a minimally invasive approach to the geniculate ganglion region in order to allow complete removal of suprageniculate disesases with low complication rates using a minimally invasive surgical route.



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Partial cricotracheal resection for severe upper tracheal stenosis: Potential impacts on the outcome

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Publication date: Available online 28 March 2017
Source:Auris Nasus Larynx
Author(s): Ahmed Musaad Abd El-Fattah, Hisham Atef Ebada, Hazem Emam Amer, Mohammed Mohammed Abosamra, Ali Tawfik
ObjectiveThe aim of this study was to investigate the potential impact of multiple preoperative and intraoperative variables on the outcome of partial cricotracheal resection and tracheal resection anastomosis (PCTR/TRA).MethodsThe study was conducted on 35 consecutive patients of grade III and IV upper tracheal stenosis with or without subglottic involvement. The indication of PCTR/TRA was post intubation stenosis in all patients. Overall complications (major and minor) occurred in 18 patients. Perioperative mortality occurred in 1 patient. Anastomotic complications do not always mean failure of surgery. They may indicate one or more interventions; such as removal of granulation tissue or dilatation of restenosis, with good results in most cases.ResultsAt the end of treatment, 30 (85.7%) patients were decannulated successfully with effortless breathing and with good phonation and swallowing. Several perioperative factors were found to have a significant impact on the outcome of PCTR/TRA. Of these factors, comorbidities had the most significant negative impact, and indeed all the three patients who had comorbidities, were not successfully decannulated. Duration of intubation, length of resected segment and previous open airway interventions was reported to have a significant negative impact on the outcome of surgery.ConclusionPCTR/TRA for treatment of post traumatic subglottic or upper tracheal stenosis has a high success rate, especially in healthy patients without comorbidities, and without previous open airway interventions.



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ATA Signal e-News March 2017 Secretary’s Update

Signal e-news March 2017

Secretary's Annual Report

 

Victor J. Bernet, MD
Victor J. Bernet, MD

Secretary/Chief Operating Officer

Secretary's Update, March 2017

 

Well, Spring is here and so is the ATA Spring 2017 Satellite Symposium in Orlando, Hypothyroidism: Where Are We Now? This activity is being held 31 March, 2017 between 1:00 and 5:30 pm in the Orange County Convention and Exhibition Center. We hope to see you there! Also, we would very much like to hear your thoughts on potential topics for future symposia.

To indirectly quote Bobbi Smith: we have so many ATA irons in the fire to the point of inducing dizziness. Hyperbole, maybe, but actually not so far from the truth. ATA leadership and committees continue to move forward on initiatives related to our strategic plan. So let's review: Strategic focus on efforts for patients. Well, the Spring Symposia will include a first ever patient panel and a remarkable 11,969 patients have completed a survey, the results of which will be discussed at the symposium. The ATA is also reaching out to patients thru Philip James who hosts the "Doctor Thyroid" podcast series at www.docthyroid.com. He has already interviewed several ATA members and these excellent podcasts are available on the listed website. Furthermore, the ATA headquarters' staff, with support from our consultants at Just Write Solutions, has just submitted an application to participate in the NIH Program "All of Us." If successful, the ATA will receive funding to support patient recruitment and education for this initiative with a special focus on underrepresented groups with thyroid disease within the United States.

Strategic focus on global leadership. We have made several advances. Members Elizabeth Pearce and Angela Leung, composed a letter to request that iodine be included as an essential micronutrient within the strategic plan for the NIH Nutrition Research Task Force (NRTF). The ATA is also involved in an effort to develop modules for primary care thyroid education in India. Furthermore, arrangements have been made with sister societies such as SNMMI to have shared symposia at our respective national meetings. The ATA expressed our concerns about the unintended negative consequences on medical research and international collaboration that the proposed executive order on travel restrictions can be anticipated to engender in several ways: a letter to the White House, a press release on the website and to the public media through NewsWise.

Strategic focus to support research efforts. With support from Rebecca Schweppe, the Research Committee plus assists by Tony Hollenberg and Tony Bianco, the ATA is in negotiations with representatives from the Nuclear Receptor Signaling Atlas (NURSA) soon to be known as Signaling Pathways to develop a data repository for thyroid diseases. This partnership is expected to make a panoply of raw data from various basic science projects available for further analysis with the intent of leading to additional research and meaningful discoveries. The Research Committee is also in the midst of reviewing submissions for awarding of research grants. We appreciate the continuing support from ThyCa, Bite Me Cancer, and the ATA Campaign endowment which make these research funds available.

The ATC Guidelines Policy Task Force continues its efforts. A new initiative with these guidelines is that arrangements have been made to support very methodical literature reviews which will hopefully strengthen the guidelines and facilitate guideline acceptance by the National Guidelines Clearinghouse which represents the newest in guideline standards.

Finally, the webpage for the 87th Annual Meeting of the ATA in Victoria, British Columbia, is open with preliminary information on program http://ift.tt/2oj2wTB. Regular abstract submissions open 29 March, 2017 with a submission deadline of June 7th. The annual program this year is shaping to be a great one and the Program Committee will be adding a Pediatric Symposium to the annual meeting agenda as well.

And with that, are you dizzy yet?

We hope to see you at the symposium in Orlando and please visit the ATA exhibit booth at the ENDO Expo – come see us and say hello. I'll be looking for you!

Sincerely,

John C. Morris, MD

Victor J. Bernet, MD
Secretary/Chief Operating Officer

Copyright © 2017 American Thyroid Association

The post ATA Signal e-News March 2017 Secretary's Update appeared first on American Thyroid Association.



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pH-Responsive pHLIP (pH Low Insertion Peptide) Nanoclusters of Superparamagnetic Iron Oxide Nanoparticles as a Tumor-selective MRI Contrast Agent

Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Yushuang Wei, Rufang Liao, Abdulrahman Ahmed Mahmood, Haibo Xu, Qibing Zhou
Superparamagnetic iron oxide nanoparticles (SPION) are contrast agents used for noninvasive tumor magnetic resonance imaging (MRI). SPION with active targeting by tumor-specific ligands can effectively enhance the MRI sensitivity and specificity of tumors. However, the challenge remains when the tumor specific markers are yet to be determined, especially in the case of early tumor detection. In this study, the effectiveness of pH-responsive SPION via a pH low insertion peptide (pHLIP) to target tumor acidic microenvironments was investigated. Polylysine polymers were first successfully modified with pHLIP to have the pH-responsive capability. SPION pHLIP nanoclusters of 64, 82, 103, and 121 nm size were then assembled by the pH-responsive polymers in a size-controlled manner. The pH-responsive SPION nanoclusters of the 64 nm size exhibited the most effective pH-responsive retention in cells and tumor selective imaging in MRI. More importantly, the unique contrast enhancement of tumor inner core by the pH-responsive SPION in three different tumor models demonstrated the clinical potential to target tumor acidic microenvironment through pHLIP for tumor early detection and diagnosis by MRI.Statement of SignificanceDetection and diagnosis of tumors at early stage are critical for the improvement of the survival rate of cancer patients. However, the challenge remains when the tumor specific markers are unto be determined, especially in early tumor detection. pH low insertion peptide (pHLIP) has been used as a specific ligand to target the tumor acidic microenvironment for tumors at early and metastatic stages. Superparamagnetic iron nanoparticles (SPION) are contrast enhancing agents used in the noninvasive magnetic resonance imaging for tumors. This research has demonstrated that pH-responsive pHLIP nanoclusters of SPION were able to target different tumors and facilitate the noninvasive diagnosis of tumors by MRI.

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Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease

Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): David Lee, Qiaozhi Lu, Sven D. Sommerfeld, Amanda Chan, Nikhil G. Menon, Tannin A. Schmidt, Jennifer H. Elisseeff, Anirudha Singh
Hyaluronic acid (HA) solutions effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms. However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation. Conversely, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Here, we developed an HA-eye drop formulation that selectively binds and retains HA for extended periods of time on the ocular surface. We synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binding either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. HA solution was mixed with the polymer-peptide system and tested on both ex vivo and in vivo models to determine its ability to prolong HA retention. Furthermore, rabbit ocular surface tissues treated with binding peptides and HA solutions demonstrated superior lubrication with reduced kinetic friction coefficients compared to tissues treated with conventional HA solution. The results suggest that binding peptide-based solution can keep the ocular surface enriched with HA for prolonged times as well as keep it lubricated. Therefore, this system can be further developed into a more effective treatment for dry eye patients than a standard HA eye drop.Statement of SignificanceEye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a standard HA eye drop.

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Comparative analysis of biological effect of corannulene and graphene on developmental and sleep/wake profile of zebrafish larvae

Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Xiang Li, Yuan Zhang, Xu Li, DaoFu Feng, ShuHui Zhang, Xin Zhao, DongYan Chen, ZhiXiang Zhang, XiZeng Feng
Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. In this study, we compared the effect of corannulene (non-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. First, the toxicity of graded doses of corannulene (1, 10, and 50 μg/mL) was tested in developing zebrafish embryos. Corannulene showed minimal developmental toxicity only induced an epiboly delay. Further, a significant decrease in locomotion/increase in sleep was observed in larvae treated with the highest dose (50 μg/mL) of corannulene while no significant locomotion alterations were induced by graphene. Finally, the effect of corannulene or graphene on the hypocretin (hcrt) system and sleep/wake regulators such as hcrt, hcrt G-protein coupled receptor (hcrtr), and arylalkylamine N-acetyltransferase-2 (aanat2) was evaluated. Corannulene increased sleep and reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behavior and gene expression patterns. These results suggest that the corannulene has the potential to cause hypnosis-like behavior in larvae and provides a fundamental comparative understanding of the effects of corannulene and graphene on biology systems.Statement of significanceLittle is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. Here, we compare the effect of corannulene (no-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviours of larval zebrafish. And we aim to investigate the effect of curvature on biological system. First, toxicity of corannulene over the range of doses (1 μg/mL, 10 μg/mL and 50 μg/mL) was tested in developing zebrafish embryos. Corannulene has minimal developmental toxicity, only incurred epiboly delay. Subsequently, a significant decrease in locomotion/increase in sleep at the highest dose (50 μg/mL) was detected in corannulene treated larvae while no significant locomotion alterations was induced by graphene. Finally, the impact of corannulene or graphene on hypocretin system and sleep/wake regulator such as hcrt, hcrtr and aanat2 was evaluated. Corannulene increased sleep, reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behaviours and gene expression patterns. This result may indicate the potential effect of corannulene to cause hypnosia-like behaviour in larvae and provide the fundamental understanding for the biological effect of curvature on biology system.

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Non-invasive Monitoring of In Vivo Degradation of a Radiopaque Thermoreversible Hydrogel and Its Efficacy in Preventing Post-operative Adhesions

Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Kewen Lei, Yipei Chen, Jinyao Wang, Xiaochun Peng, Lin Yu, Jiandong Ding
In vivo behavior of hydrogel-based biomaterials is very important for rational design of hydrogels for various biomedical applications. Herein, we developed a facile method for in situ fabrication of radiopaque hydrogel. An iodinated functional diblock copolymer of poly(ethylene glycol) and aliphatic polyester was first synthesized by coupling the hydroxyl end of the diblock copolymer with 2, 3, 5-triiodobenzoic acid (TIB) and then a radiopaque thermoreversible hydrogel was obtained by mixing it with the virgin diblock copolymer. A concentrated aqueous solution of the copolymer blend was injectable at room temperature and spontaneously turned into an in situ hydrogel at body temperature after injection. The introduction of TIB moieties affords the capacity of X-ray opacity, enabling in vivo visualization of the hydrogel using Micro-CT. A rat model with cecum and abdominal defects was utilized to evaluate the efficacy of the radiopaque hydrogel in the prevention of post-operative adhesions, and a significant reduction of the post-operative adhesion formation was confirmed. Meanwhile, the maintenance of the radiopaque hydrogel in the abdomen after administration was non-destructively detected via Micro-CT scanning. The reconstructed three-dimensional images showed that the radiopaque hydrogel with an irregular morphology was located on the injured abdominal wall. The time-dependent profile of the volume of the radiopaque hydrogel determined by Micro-CT imaging was well consistent with the trend obtained from the dissection observation. Therefore, the radiopaque thermoreversible hydrogel can serve as a potential visualized biomedical implant and this practical mixing approach is also useful for further extension into the in vivo monitoring of other biomaterials.Statement of SignificanceWhile a variety of biomaterials have been extensively studied, it is rare to monitor in vivo degradation and medical efficacy of a material after being implanted deeply into the body. Herein, the radiopaque thermoreversible hydrogel developed by us not only holds desirable performance on the prevention of post-operative abdominal adhesions, but also allows non-invasive monitoring of its in vivo degradation with CT imaging in a real-time, quantitative and three-dimensional manner. The methodology based on CT imaging provides important insights into the in vivo fate of the hydrogel after being deeply implanted into mammals for different biomedical applications and significantly reduces the amount of animals sacrificed.

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Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response

Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Daniel Kulakowski, Ariene A Leme-Kraus, Joo-won Nam, James McAlpine, Shao-Nong Chen, Guido F. Pauli, Sriram Ravindran, Ana K. Bedran-Russo
Proanthocyanidins (PACs) are plant-derived, multifunctional compounds that possess high interactivity with extracellular matrix (ECM) components. The documented affinity of PACs for type-I collagen is directly correlated with their structural features and degree of polymerization. In this investigation, centrifugal partition chromatography (CPC) was used to sequentially deplete less active monomeric and polymeric PACs from a crude Pinus massoniana bark extract to create refined mixtures enriched in oligomeric PACs. The ability of these oligomeric PACs to modify the mechanical properties of the dentin collagen matrix and their biocompatibility with dental pulp cells (DPCs) was evaluated in an innovative biomimetic environment. The refined mixtures displayed high interactivity with dentin collagen as demonstrated by a significant increase (> 5-fold) in the modulus of elasticity of the dentin matrix. In a simplified model of the dentin-DPC complex, DPCs embedded within their native ECM in the presence of PAC-treated dentin exhibited increased proliferation. Quantitative gene expression analyses indicated that exposure to PAC-treated dentin increased the expression of key biomineralization and odontogenic differentiation regulators, including RUNX2, BMP2, OCN, and DSPP. LC-MS/MS analysis revealed that PACs two to four units long (dimers, trimers, and tetramers) were being released from dentin into media, influencing cell behavior. Overall, the results suggested that PAC dimers, trimers, and tetramers are not only biocompatible, but enhance the differentiation of DPCs towards a phenotype that favors biomineralization. PAC-enriched refined mixtures can influence the field of biomaterials and regeneration by serving as renewable, non-cytotoxic agents that can increase the mechanical properties of biomaterials.Statement of SignificancePine bark extract is a renewable source of structurally diverse proanthocyanidins (PACs), multifunctional compounds whose interaction with collagen can be tailored to specific purposes by enrichment of selected PACs from the complex mixture. Oligomeric PACs were enriched from the extract and were shown here to sustain desired tissue modification and were thus assessed for cellular response in a model of the dentin-pulp interface. This model was developed to mimic leaching of potentially reactive compounds into pulp tissue. Dental pulp cells exposed to PAC-treated dentin showed increased proliferation and expression of genes necessary for extracellular matrix deposition and biomineralization, processes crucial for forming new dentin. Thus, collagen-interactive PACs may also enhance tissue regeneration and have broad impact in tissue engineering.

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