Head and Neck Diseases by Alexandros G.Sfakianakis: 03/07/17

Τρίτη 7 Μαρτίου 2017

Follicular Porokeratosis, a Porokeratosis Variant.

Porokeratosis derives from a process of abnormal keratinization, resulting in clinical and histologic variants. Follicular involvement is infrequently described, with previous suggestions that it may represent a distinct condition. We describe a case of typical disseminated superficial actinic porokeratosis with additional clinically prominent folliculocentric keratosis. Histologically, this represented follicular cornoid lamellae. These findings support follicular porokeratosis as an anatomic site variant of porokeratosis, as opposed to a distinct condition. We also want to raise awareness of this variant which clinically should be considered when presented with a discrete papular keratotic eruption. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Allergic laryngitis: unraveling the myths.

Purpose of review: This article provides a thorough review of the literature highlighting the articles that have advanced our knowledge about the sensitivity of the larynx to allergens in the air or ones consumed. This area of inquiry requires continued interest and investigation. As the field of clinical laryngology changes, and more information is discovered about the possible causal association between allergy and vocal pathologies, practicing otolaryngologists, allergists, and other medical professionals may discover more comprehensive methods to evaluate and treat their allergic patients, particularly those who present with complaints of dysphonia, dysphagia, laryngopharyngeal reflux (LPR), and/or dyspnea. Recent findings: There continues to be epidemiological studies designed to describe the relationship of allergy to vocal symptoms and signs. Both population and smaller studies have recently attempted to link these two conditions. Unfortunately, the patient with chronic laryngeal complaints is often tagged by default with the diagnosis of LPR and treated with proton pump inhibitors, which are not always beneficial. The endoscopic assessment may not be as reliable to make the diagnosis of LPR as the examination is subjective and the inter-rater reliability is low. It has been demonstrated by direct laryngeal provocation studies that sticky-viscous endo-laryngeal mucous is the only reliable finding consistently associated with allergy potential allergic tissue reactivity. Summary: The interrelationship of allergic sensitivity and chronic laryngitis in certain individuals is becoming clearer because our knowledge of inquiry has increased and the available routine technology to diagnose these conditions has remarkably improved. Notwithstanding these advancements, much more research is needed on this subject to reduce the frequency of mis-diagnoses and mis-management of allergic patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Patient adherence to swallowing exercises in head and neck cancer.

Purpose of review: A younger population and improved treatments for head and neck cancer (HNC) mean that more people are now living longer with the consequences of treatment, including long-term swallowing problems (dysphagia). Exercises aim to improve swallowing function, however highly variable adherence rates are currently reported, with no standard measure of adherence. Recent findings: Measuring adherence to swallowing exercises depends on the definition of 'adherence', the tools used to measure adherence, and the acceptable threshold that is used to constitute adherence or nonadherence. Particular barriers to swallowing exercise adherence include the burden of treatment, the commitment required to undertake a home-based exercise programme and the difficulty in motivating patients to exercise before swallowing problems have become apparent. Findings from the wider literature on general exercise interventions highlight the importance of external and patient-related factors on adherence, including patient beliefs, social support, self-regulation and goal setting. Summary: Key barriers and motivators to adherence are presented, which will have implications for the design of future swallowing exercise interventions. The relevance of behaviour change theory in facilitating adherence is highlighted, with ongoing studies used to exemplify how behaviour change components and analysis of patient beliefs can be incorporated into intervention development. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The local twitch response during trigger point dry needling: Is it necessary for successful outcomes?

Publication date: Available online 7 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Thomas Perreault, James Dunning, Raymond Butts
BackgroundMyofascial trigger point (MTrP) injection and trigger point dry needling (TrPDN) are widely accepted therapies for myofascial pain syndrome (MPS). Empirical evidence suggests eliciting a local twitch response (LTR) during needling is essential.ObjectiveThis is the first review exploring the available literature, regardless of study design, on the neurophysiological effects and clinical significance of the LTR as it relates to reductions in pain and disability secondary to MTrP needling.MethodsPubMed, MEDLINE, Science Direct and Google Scholar were searched up until October 2016 using terms related to trigger point needling and the LTR.Resultsand Discussion: Several studies show that eliciting a LTR does not correlate with changes in pain and disability, and multiple systematic reviews have failed to conclude whether the LTR is relevant to the outcome of TrPDN. Post needling soreness is consistently reported in studies using repeated in and out needling to elicit LTRs and increases in proportion to the number of needle insertions. In contrast, needle winding without LTRs to MTrPs and connective tissue is well supported in the literature, as it is linked to anti-nociception and factors related to tissue repair and remodeling. Additionally, the positive biochemical changes in the MTrP after needling may simply be a wash out effect related to local vasodilation. While the LTR during TrPDN appears unnecessary for managing myofascial pain and unrelated to many of the positive effects of TrPDN, further investigation is required.

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Optical Coherence Tomography and Neuro-Ophthalmology.

No abstract available

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A Retrospective Analysis of the Efficacy of Pembrolizumab in Melanoma Patients With Brain Metastasis

A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab. Twenty-six (72%) patients with BM had received prior treatment for BM. With median follow-up of 17.2 months, 54 patients (61%) developed progressive disease on pembrolizumab. Intracranial progression occurred in 19 patients (21%), 3 of whom did not have BM before treatment. Median time to progression at any site was 6 months for those without BM (n=53), 5 months for those with treated BM (n=26), and 1.2 months for patients with untreated BM (n=10). Using a Cox regression model adjusted for baseline factors, there was a statistically significant (Wald χ2P=0.003) reduction in the hazard of progression for patients without BM [hazard ratio, 0.19; 90% confidence interval, 0.08–0.42) and patients with treated BM (hazard ratio, 0.27; 90% confidence interval, 0.12–0.64) compared with those with untreated BM. In conclusion, melanoma patients with pretreated BM can have durable systemic responses to pembrolizumab. Large, prospective studies are needed to evaluate the intracranial antitumor activity of pembrolizumab in melanoma patients with untreated BM.

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A Novel Fusion Antibody Exhibits Antiangiogenic Activity and Stimulates NK Cell-mediated Immune Surveillance Through Fused NKG2D Ligand

A single-chain variable fragment (scFv) targeting vascular endothelial growth factor receptor 2 was previously generated from a phage display library in our laboratory. However, it has shortened half-life and lacks Fc fragment for effector cell recognition. To address these challenges, a ligand of NK-cell receptor NKG2D was fused to the scFv and created a fusion protein scFv-major histocompatibility complex class I-related chain A (MICA), which is expected to recognize tumor cells through the scFv moiety and stimulate NK cells through the MICA. The fusion protein demonstrated specific binding to both vascular endothelial growth factor receptor 2 and NKG2D in protein-based and cell-based assays. In addition, it demonstrated antiangiogenic activities including restraining the proliferation, migration, transwell invasion, and tube formation of human umbilical vein endothelial cells. Furthermore, the fusion protein exhibited significant cytotoxicity on K562, MDA-MB-435, and B16F10 cells and triggered NK92 cell-mediated cytotoxicity on MDA-MB-435 cells by stimulating the release of significant cytokines. The fusion protein targeting strategy, therefore, provides a means to engage lymphocyte effector cells against tumor specific antigen overexpressing tumor cells.

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Use of Engineered Exosomes Expressing HLA and Costimulatory Molecules to Generate Antigen-specific CD8+ T Cells for Adoptive Cell Therapy

Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8+ T cells both directly and indirectly via CoEX-A2 cross-dressed cells. Notably, CoEX-A2s also generated similar levels of HCMV pp65-specific and MART1-specific CD8+ T cells as DEX in vitro. The results suggest that these novel exosomes may provide a crucial reagent for generating antigen-specific CD8+ T cells for adoptive cell therapies against viral infection and tumors.

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Possible Compartmental Cytokine Release Syndrome in a Patient With Recurrent Ovarian Cancer After Treatment With Mesothelin-targeted CAR-T Cells

Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies. A 52-year-old woman with BRCA 1 mutation positive heavily pretreated advanced recurrent serous ovarian cancer was treated under a compassionate use protocol with autologous mesothelin-redirected chimeric antigen receptor T cells (CART-meso). Autologous T cells were transduced to express a receptor composed of an extracellular antimesothelin single-chain variable fragment fused to 4-1BB and TCR-zeta signaling domain. This patient was infused with 3×107 CART-meso T cells/m2 without lymphodepletion and developed compartmental CRS confined to the pleural cavities. The compartmental CRS was evidenced by an increase in IL-6 and accumulation of CART-meso T cells in pleural fluid compared with peripheral blood and was successfully treated the anti-IL6 receptor antagonist tocilizumab on D21 after the T-cell infusion. This is the first description of a compartmental CRS in a patient with solid malignancy. This response could be due to malignant pleural fluid creating an environment where T cells could interact with tumor cells and suggests localized on-target CAR-T-cell activation.

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Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder

Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy. This is the first case, to our knowledge, reported in association with bladder cancer. The precise diagnosis of MG has important implications on management, as treatment with steroids can transiently worsen myasthenia in nearly 50% of cases.

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Unenhanced computed tomography for normal appendix detection: comparison of low-dose with statistical iterative reconstruction and regular-dose with filtered back projection

Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): Hwi Ryong Park, Sung Bin Park, Eun Sun Lee, Hyun Jeong Park, Jong Beum Lee, Yang Soo Kim
PurposeTo evaluate the differences in visualization of a normal appendix between regular-dose (RD) and low-dose (LD) unenhanced CT.Material and methods179 patients underwent both RDCT and LDCT for urolithiasis. Two reviewers evaluated the appendiceal visualization on a three-point scale. Sensitivities and interobserver agreement were measured.ResultsThere were no significant differences between RDCT and LDCT in sensitivity, regardless of the reviewer. Interobserver agreement was excellent in both RDCT and LDCT.ConclusionUnenhanced LDCT is a good tool for detecting a normal appendix and is also useful for less experienced interpreters who are unfamiliar with using LDCT images.

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Urban Residence, Neighborhood Poverty, race/ethnicity and Asthma Morbidity Among Children in Medicaid

Publication date: Available online 8 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Corinne A. Keet, Elizabeth Matsui, Meredith C. McCormack, Roger Peng
BackgroundAlthough poor-urban (inner-city) areas are thought to have high asthma prevalence and morbidity, we recently found that inner-cities do not have higher prevalent pediatric asthma. Whether asthma morbidity is higher in inner-city areas across the U.S. not known.ObjectiveTo examine relationships between residence in poor and urban areas, race/ethnicity, and asthma morbidity among children with asthma enrolled in Medicaid.MethodsChildren aged 5-19 enrolled in Medicaid in 2009-2010 were included. Asthma was defined by at least one outpatient or emergency department (ED) visit with a primary diagnosis code of asthma over the 2 year period. Urbanization status was defined at the county level and neighborhood poverty at the zip-code level. Among children with asthma, logistic models were created to examine the effects of urbanization, neighborhood poverty and race/ethnicity on rates of asthma outpatient visits, ED visits and hospitalizations.Results16,860,716 children were included (1,534,820 with asthma). Among children enrolled in Medicaid, residence in inner-city areas did not confer increased risk of prevalent asthma in either crude or adjusted analyses, but was associated with significantly more asthma-related emergency room visits and hospitalizations among those with asthma in crude analyses (RR 1.48, 95%CI:1.24-1.36 and 1.97, 95%CI:1.50-1.72, respectively) and when adjusted for race/ethnicity, age and gender (aRR 1.23, 95%CI:1.08-1.15 and 1.62, 95%CI:1.26-1.43). Residence in urban or poor areas, and non-Hispanic black race/ethnicity were all independently associated with increased risk of asthma related emergency room visits and hospitalizations.ConclusionsResidence in poor and urban areas is an important risk factor for asthma morbidity, but not prevalence, among low-income U.S. children.

Teaser

Among children enrolled in Medicaid, residence in an urban area is not a risk factor for prevalent asthma, but residence in urban or poor areas, and Black race/ethnicity are each independent risk factors for asthma emergency room visits and hospitalizations.

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Fatal anaphylaxis in France: analysis of national anaphylaxis data, 1979-2011

Publication date: Available online 7 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Guillaume Pouessel, Claire Claverie, Julien Labreuche, Aimée Dorkenoo, Jean-Marie Renaudin, Mireille Eb, Stéphanie Lejeune, Antoine Deschildre, Stéphane Leteurtre

Teaser

The anaphylaxis mortality rate has fallen about 2% per year in France over the past 3 decades. Increased awareness of anaphylaxis treatment guidelines will hopefully continue this trend.

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Circulating Gluten-Specific FOXP3+CD39+ Regulatory T Cells Have Impaired Suppressive Function in Celiac Disease

Publication date: Available online 8 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Laura Cook, C. Mee Ling Munier, Nabila Seddiki, David van Bockel, Noé Ontiveros, Melinda Y. Hardy, Jana K. Gillies, Megan K. Levings, Hugh Reid, Jan Peterson, Jamie Rossjohn, Robert P. Anderson, John Zaunders, Jason A. Tye-Din, Anthony D. Kelleher
BackgroundCeliac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in celiac disease has been well characterized, the role of regulatory T-cells (Tregs) in the loss of tolerance to gluten remains poorly understood.ObjectiveTo define if celiac disease patients have a dysfunction or lack of gluten-specific FOXP3⁺ Tregs.MethodsTreated celiac disease patients underwent oral wheat challenge to stimulate re-circulation of gluten-specific T-cells. Peripheral blood was collected pre- and post-challenge. In order to comprehensively measure the gluten-specific CD4⁺ T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4⁺ T-cells that does not rely on tetramers, antigen-stimulated cytokine production or proliferation, but rather on antigen-induced co-expression of CD25 and OX40 (CD134).ResultsThe number of circulating gluten-specific Tregs and effector T-cells both increased significantly post oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4⁺ T-cells were FOXP3⁺CD39⁺ Tregs, which reside within the pool of memory CD4⁺CD25⁺CD127^lowCD45RO⁺ Tregs. Although we observed normal suppressive function in peripheral polyclonal Tregs from celiac patients, after a short in vitro expansion the gluten-specific FOXP3⁺CD39⁺ Tregs exhibited significantly reduced suppressive function compared to polyclonal Tregs.ConclusionThis study provides the first estimation of FOXP3⁺CD39⁺ Treg frequency within circulating gluten-specific CD4⁺ T-cells following oral gluten challenge of celiac patients. FOXP3⁺CD39⁺ Tregs comprised a major proportion of all circulating gluten-specific CD4⁺ T-cells but had impaired suppressive function, indicating that Treg dysfunction may be a key contributor to disease pathogenesis.

Teaser

We performed a novel study of gluten-specific FOXP3⁺ Tregs in patients with celiac disease and found that, although these cells comprise the majority of circulating gluten-specific CD4⁺ T-cells, they have impaired suppressive function.

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IgE and antiviral immune response in asthma

Publication date: Available online 6 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Jonathan S. Tam, Mitchell H. Grayson

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Reply

Publication date: Available online 6 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): David B. Kantor, Wanda Phipatanakul, Joel N. Hirschhorn

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Prevention of Flares in Children with Atopic Dermatitis with Regular Use of an Emollient Containing Glycerol and Paraffin: A Randomized Controlled Study

Abstract

Background/Objectives

Emollients are part of the standard treatment for atopic dermatitis (AD), although there is limited evidence that regular use of emollients as management therapy reduces the frequency of flares and corticosteroid consumption. The objective of this study was to evaluate the benefit of emollient use in the management of mild to moderate AD in children by assessing the ability of two different emollients (particularly V0034CR) to prevent flares and to reduce the use of corticosteroids.

Methods

In this randomized, open-label study, patients with a current flare were treated with a potent topical corticosteroid. After flare resolution, patients were centrally randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio) for 12 weeks. New flares were medically assessed before being treated with a moderately potent corticosteroid.

Results

A total of 335 children 2 to 6 years of age were randomized. At 12 weeks, the percentage of patients with one or more flares was statistically significantly lower with V0034CR (35.1%) than without emollient (67.6%; p < 0.001). Fewer patients treated with V0034CR required any corticosteroids or immunosuppressants (23.6%) than patients with no emollient (43.3%) at 12 weeks. The difference was significant at all time points (p = 0.002). Patients treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, lower Investigator Global Assessment scores, and lower Scoring Atopic Dermatitis scores than those who were not. V0034CR was well tolerated, with no specific safety concerns.

Conclusion

Regular emollient use in children with mild to moderate AD reduces flares and corticosteroid consumption.

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An evaluation of our experience in position verification of catheters used for interstitial high-dose-rate brachytherapy of solitary bladder tumors

Publication date: Available online 6 March 2017
Source:Brachytherapy
Author(s): S.J.E.A. Bus, N.G. Leus, B.J. Oosterveld, M.P.R. Van Gellekom, G.J.M. van de Loop, E.M. van der Steen-Banasik
PurposeThe goal of this study was to verify the position of catheters used over 4 days for brachytherapy of solitary bladder tumors.Methods and MaterialsThe study covered three phases. Shifting of catheters was studied using daily position verification CT scans of 20 patients. The possibility to omit the CT scan on Day 2 by adding a loading margin of 4 mm on each side was studied using data of 5 patients. Whether the Day 4 verification CT scan could be omitted if this margin was used, was studied for another group of 10 patients, comparing the Day 3 treatment plan to the Day 4 CT scan.ResultsAn average catheter shift on Days 2, 3, and 4 of, respectively, −0.3 mm (−8 to 10 mm), −0.5 mm (−14 to 10 mm), and −0.1 mm (−16 to 28 mm) was found over the measurements at both sites of the catheter. Including only shifts causing underdosing of the clinical target volume (CTV), the average shift on Days 2, 3, and 4 was, respectively, −3.6 mm (−1 to −8 mm), −5.4 mm (−1 to −14 mm), and −5.3 mm (−1 to −16 mm). After adding a loading margin, the CTV was covered on Day 2; however, the margin was not sufficient for Days 3 and 4. On Day 4, in 2/10 patients, the CTV was not completely covered. In 5/10 patients, an increased 200% isodose volume was found.ConclusionsPosition verification is necessary in bladder brachytherapy. If a 4-mm margin on each side of the loading pattern was added, position verification on Day 2 could be omitted. The verification CT scan of Days 3 and 4 is still necessary.

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Infection control III: Infection prevention and control as mediators

Publication date: Available online 7 March 2017
Source:American Journal of Infection Control
Author(s): Harold W. Horowitz

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Could legal requirements in nursing practice trigger actions that would change the rates of urinary tract infections? A case study in Brazil

Publication date: Available online 7 March 2017
Source:American Journal of Infection Control
Author(s): Clesnan Mendes-Rodrigues, Eliana Borges Silva Pereira, Renata Lemos de Sousa Neto, Jaqueline Resende, Astrídia Marília de Souza Fontes
We evaluated the influence of a Brazilian resolution, published in 2013, that restricts the performing of urinary catheterization to nurses, as opposed to others from different nursing professional categories, on indicators of catheter-associated urinary tract infection in an intensive care unit. The resolution triggered actions such as the implementation of protocols and nursing staff training that led to behavior changes related to the reduction of catheter-associated urinary tract infection rates.

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Nursing students' knowledge about ventilator-associated pneumonia prevention guidelines: Effectiveness of a teaching program

Publication date: Available online 7 March 2017
Source:American Journal of Infection Control
Author(s): Sami M. Aloush
This study evaluated the effectiveness of an educational course that aimed to expand student nurses' knowledge about the guidelines for ventilator-associated pneumonia (VAP) prevention. In the pretest, the students revealed poor knowledge (mean score ± SD, 6.3 ± 2.8 out of 20). After completion of the educational program, participants in the experimental group showed a significant improvement (t105 = 14.9, P < .001). The control group showed no significant improvement. More focus on VAP prevention guidelines is essential in nursing curricula.

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An Epstein-Barr Virus-Positive Classical Hodgkin Lymphoma with Exclusive Sinusoidal Growth Pattern: An Unusual Morphologic Variant

Publication date: Available online 7 March 2017
Source:Pathology - Research and Practice
Author(s): Pu Su, Rachel Jug, Xin Liu, Endi Wang
Classical Hodgkin lymphoma (cHL) typically involves lymph node parenchyma, and a case with Hodgkin cells confined within nodal sinusoids is extremely rare. Herein we report a case of cHL with sinusoidal growth pattern. This 15-year old patient presented with B symptoms and was found to have bilateral cervical lymphadenopathy and an anterior mediastinal mass. Biopsy of a cervical lymph node demonstrated cohesive clusters of Reed-Sternberg (RS)-like cells suggestive of sinusoidal growth with an extrasinusoidal mixed inflammatory cell infiltrate characteristic of the microenvironment seen in cHL. The RS cells/variants were positive for CD30 and CD15, and showed down-regulation of B-cell program and CD45, an immunophenotypic profile consistent with cHL. The sinusoidal growth pattern was also highlighted by EBV study. To the best of our knowledge, this is the first case of EBV-positive cHL that displays a sinusoidal growth pattern. The patient was treated with children's high risk cHL chemotherapy protocol and responded well.

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Defects of Thyroid Hormone Synthesis and Action

Publication date: Available online 6 March 2017
Source:Endocrinology and Metabolism Clinics of North America
Author(s): Zeina C. Hannoush, Roy E. Weiss

Teaser

Congenital hypothyroidism (CH) is the most common inborn endocrine disorder and causes significant morbidity. To date, we are only aware of the molecular basis responsible for the defects in a small portion of patients with CH. A better understanding of the pathophysiology of these cases at the genetic and molecular basis provides useful information for proper counseling to patients and their families a well as for the development of better targeted therapies. This review provides a succinct outline of the pathophysiology and genetics of the known causes of thyroid dysgenesis, dyshormonogenesis, and syndrome of impaired sensitivity to thyroid hormone.

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The reproducibility and clinical utility of the 3D camera for measuring scar height, with a protocol for administration

Background

This study aimed to determine the reproducibility and clinical utility of a 3D camera for measuring burn scar height in adults.

Methods

Participants from a larger prospective longitudinal study were included. Reproducibility data were collected using an immediate test-retest interval and a 1-2 week test-retest interval and included reliability and agreement. The LifeViz^™ 3D camera was used to measure scar height. Reproducibility was tested using the Intraclass Correlation Coefficient (ICC), percentage agreement within 1 mm between test and retest, standard error of measurement, smallest detectable change (SDC) and Bland Altman limits of agreement.

Results

Burn scar images from 55 adult participants were included. Intra-rater reliability was acceptable using an immediate retest interval (maximum and minimum height ICC=0.85, 0.86 respectively). Agreement using an immediate retest interval was borderline acceptable (maximum and minimum height SDC=1.11, 0.69 respectively) to detect changes of close to 1 mm. Reproducibility was largely not acceptable using a 1-2 week test-retest interval (eg, maximum and minimum height ICC=0.34, 0.68 respectively; maximum and minimum height SDC=2.66, 1.16). The clinical utility of the camera was supported for scars over relatively flat areas and well-defined border margins. A protocol for administration of the camera was developed.

Conclusion

The 3D camera appears capable of detecting gross changes or differences in scar height above the normal skin surface, in adults with scars over relatively flat areas and well-defined border margins. However, further testing of reproducibility using a shorter test-retest interval than 1-2 week retest is recommended to confirm the suitability of the device for measuring changes or differences in scar height.

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Examination of wound healing after curettage by multiphoton tomography of human skin in vivo

Background

The multiphoton tomography (MPT) has evolved into a useful tool for the non-invasive investigation of morphological and biophysical characteristics of human skin in vivo. Until now, changes of the skin have been evaluated mainly by using clinical and histological techniques. In this study, the progress of wound healing was investigated by MPT over 3 weeks with a final examination after 24 months. Especially, the collagen degradation, reepithelization and tissue formation were examined. As specific parameter for wound healing and its course the second-harmonic generation-to-autofluorescence aging index of dermis (SAAID) was used.

Methods

About 10 volunteers aged between 25 and 58 years were examined. Acute wounds were scanned with three Z-stacks taken per visit. The stacks were taken up to a depth of 225 μm at increments of 5 μm and a scan time for 3 seconds per scan. Subsequently, the SAAID was evaluated as an indicator for wound healing. Furthermore, single scans were taken for morphological investigations.

Results

The evaluation revealed a distinct difference in the SAAID behavior between the Z-stacks taken at each visit. Furthermore, the degradation of collagen and cells and their reappearance could be shown in the course of the visits.

Conclusions

Clear differences in the curve behavior of the SAAID at every visit were shown in this study. The SAAID curves and morphological images could be correlated with findings of the clinical examination of different wound healing phases. Therefore, SAAID curves and morphological MPT imaging could provide a non-invasive tool for the determination of wound healing phases in patients in vivo.

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Editorial board

Publication date: May 2017
Source:Biomaterials, Volume 126

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Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy

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Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Nan Lu, Peng Huang, Wenpei Fan, Zhantong Wang, Yijing Liu, Sheng Wang, Guofeng Zhang, Junkai Hu, Wenfei Liu, Gang Niu, Richard D. Leapman, Guangming Lu, Xiaoyuan Chen
The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.

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Practicality analysis of the staging system proposed by the Japan Otological Society for acquired middle ear cholesteatoma: A multicenter study of 446 surgical cases in Japan

Publication date: Available online 6 March 2017
Source:Auris Nasus Larynx
Author(s): Keiji Matsuda, Tetsuya Tono, Hiromi Kojima, Yutaka Yamamoto, Masafumi Sakagami, Yasuo Mishiro, Yasuyuki Hinohira, Taeko Okuno
ObjectiveThe Objective of this study was to assess the practicality of the cholesteatoma staging system proposed by the Japan Otological Society (JOS) for acquired middle ear cholesteatoma (the 2010 JOS staging system).MethodsBetween 2009 and 2010, 446 ears with retraction pocket cholesteatoma underwent primary surgery at 6 institutions in Japan. The extent of cholesteatoma was surgically confirmed, and classified into three stages.ResultsThe cholesteatoma affected the pars flaccida in 325 ears (73%), the pars tensa in 100 ears (22%), and both regions combined in 21 ears (5%). The hearing outcome (postoperative air-bone gaps dB) worsened as follows (Stage I, II, III): 84%, 68%, 53% in pars flaccida; 71%, 62%, 30% in pars tensa, and 42% at Stage II, and 50% at Stage III in the combined group. The incidence of residual cholesteatoma increased as follows (Stage I, II, III): 2%, 12%, 23% in pars flaccida; 7%, 30%, 21% in the pars tensa group. The severity of disease was reflected in postoperative hearing and increasing incidence of recurrence rate.ConclusionThe 2010 JOS staging system is suitable for evaluating initial pathology. It is particularly practical for standardizing reporting of retraction pocket cholesteatoma and for adjusting for the severity of the condition during outcome evaluations. It may also provide information that is useful for counseling patients.

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Protective effect of an astaxanthin nanoemulsion against neomycin-induced hair-cell damage in zebrafish

Publication date: Available online 6 March 2017
Source:Auris Nasus Larynx
Author(s): Yosuke Takemoto, Yoshinobu Hirose, Kazuma Sugahara, Makoto Hashimoto, Hirotaka Hara, Hiroshi Yamashita

http://ift.tt/2mhhskc

Promoting global action on hearing loss: World hearing day.

Promoting global action on hearing loss: World hearing day.

Int J Audiol. 2017 Mar;56(3):145-147

Authors: Chadha S, Cieza A

PMID: 28262049 [PubMed - in process]

http://ift.tt/2m0pPQv

Germ cell apoptosis and expression of Bcl-2 and Bax in porcine testis under normal and heat stress conditions

Publication date: Available online 6 March 2017
Source:Acta Histochemica
Author(s): Xiaorui Fan, Huaming Xi, Zhen Zhang, Yajun Liang, Qinghong Li, Junping He
The aim of this study was to examine whether an elevated ambient temperature (37–40°C) had an effect on the apoptosis of germ cells and the expression of Bcl-2 and Bax in porcine testis. Six boars were used. Three boars were subjected to an elevated ambient temperature (37–40°C, 7days, 3h per day) as a heat stress (HS) group. The other 3 boars were kept in a room temperature house (20–27°C) as a control group. All boars were castrated and the testes were harvested. TUNEL assay was used for the detection of apoptotic cells. Immunohistochemistry, Western blotting and quantitative real-time PCR were used to analyze protein and mRNA levels of Bcl-2 and Bax in response to heat treatment. The results showed that apoptotic signals increased under heat stress conditions compared with the control (P<0.01), and the cell types most affected by heat treatment were spermatocytes and spermatids. In both the control and experimental groups, Bcl-2 was expressed in the cytoplasm and nucleus of spermatogonia, spermatocytes and differentiating spermatids and Bcl-2 preferentially localized close to the seminiferous tubule's luminal surface in late spermatocytes and spermatids. Compared with the control group, the expression levels of Bcl-2 protein and mRNA significantly increased in heat treatment group, while the expression levels of Bax protein and mRNA did not show significant changes between the control and experimental group. Low to moderate Bax immunoreactivity staining was observed in all kinds of germ cells in the control group. Strong staining was observed in spermatogonia, and low to moderate Bax staining was observed in spermatocytes and spermatids. A redistribution of Bax from a cytoplasmic to perinuclear or nuclear localization could be observed in the spermatogonia, spermatocytes and spermatids obtained in the heat treated group. These results showed that elevated ambient temperatures induced germ cell apoptosis. In response to heat stress, the expression of Bcl-2 increased and a redistribution of Bax from a cytoplasmic to a perinuclear or nuclear localization. This indicates that Bcl-2 and Bax may be involved in regulation of germ cell apoptosis induced by heat stress in boars.

http://ift.tt/2mW0xqy

Klotho, APOEε4, cognitive ability, brain size, atrophy and survival: A study in the Aberdeen Birth Cohort of 1936

Publication date: Available online 7 March 2017
Source:Neurobiology of Aging
Author(s): Clarisse F. de Vries, Roger T. Staff, Sarah E. Harris, Dorota Chapko, Daniel S. Williams, Polina Reichert, Trevor Ahearn, Christopher J. McNeil, Lawrence J. Whalley, Alison D. Murray
A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show [1] KL-VS heterozygotes had shorter survival and [2] smaller white matter volumes than non-carriers; [3] had slower cognitive decline; and [4] had greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected. A possible explanation for these results in the context of the literature is a potential interaction between the environment and/or age of the participants, leading to a heterozygote disadvantage. The longitudinal cognitive trajectories indicate that heterozygotes would have an advantage in very late life. Collectively these results suggest that the genotype-survival advantage of the KL-VS allele is age-dependent and possibly mediated through differential cognition and brain volume.

http://ift.tt/2mDQlCD

Mobile tablet audiometry in fluctuating autoimmune ear disease

Abstract

Background

Autoimmune inner ear disease (AIED) is a rare condition characterized by bilateral fluctuating sensorineural hearing loss (SNHL). The labile nature of this hearing loss makes it difficult to accurately quantify with conventional methods, and therefore it is challenging to rehabilitate.

Methods

Over a 9-month period one pediatric patient with severe AIED was monitored and conducted home audiograms using a previously validated testing system (Shoebox Audiometry). During this period he also underwent several clinical audiograms. The correlation between clinical and home audiograms was analyzed with a Pearson coefficient, and the range and frequency of fluctuations was recorded.

Results

Sixty-four automated home audiograms and nine clinical audiograms were conducted. When tested at home using a calibrated system the pure tone average (PTA) fluctuated between 12 dB and 72 dB indicating large variability in hearing. Fluctuations were frequent: on 28 occasions the PTA varied by at least 5 dB when retested within 4 days. The mean PTA was 50 dB and 95% of the thresholds were within 36 dB of the mean. Clinical audiograms obtained on the same day or within 1 day of home testing were highly concordant (with a Pearson coefficient of 0.93).

Conclusion

AIED can result in significant fluctuations in hearing over short periods of time. Home testing enables a more granular look at variations over time and correlates well with clinical testing, and thus facilitates rapid action and informed rehabilitation.

http://ift.tt/2lW8A1T

Intraoperative Funktionsüberwachung des N. facialis

Zusammenfassung

Hintergrund

Bei Operationen an Vestibularisschwannomen gehören Schädigungen des N. facialis mit konsekutiven funktionellen Defiziten zu den bedeutendsten Komplikationen. Die intraoperative Funktionsüberwachung soll dazu dienen, diese Komplikation zu vermeiden.

Fragestellung

Welche Methoden zur intraoperativen Funktionsüberwachung haben sich entwickelt? Welche Methoden sind aktuell in Gebrauch, und welche Ziele können damit sinnvoll verfolgt werden?

Material und Methoden

Auswertung und Zusammenfassung der Literatur, Diskussion der vorhandenen Methoden und ihrer Fähigkeiten, die gesteckten Ziele zu erreichen.

Ergebnisse

Die intraoperative Funktionsüberwachung soll es ermöglichen, den N. facialis intraoperativ sicher zu identifizieren. Sie soll potenziell schädigende Ereignisse anzeigen und während der Operation eine Einschätzung über den zu erwartenden postoperativen Funktionszustand des Nervs erlauben. Zur Verfügung stehen die elektrische Direktstimulation, das freilaufende Elektromyogramm (EMG), evozierte Potenziale des N. facialis und das prozessierte EMG.

Schlussfolgerungen

Die Identifikation und Verfolgung des Nervs im Operationssitus mittels der elektrischen Direktstimulation ist gut möglich. Potenziell schädigende Ereignisse können mit allen anderen Methoden in Echtzeit oder nahezu in Echtzeit angezeigt werden. Die intraoperative Prognostik wird derzeit aber bei allen verfügbaren Methoden durch falsch-positive Untersuchungsergebnisse belastet und ist nur bedingt verlässlich.

http://ift.tt/2mDLEc9

Prävalenz von Schwerhörigkeit in Nord- und Süddeutschland

Zusammenfassung

Hintergrund

Die Untersuchung HÖRSTAT im Nordwesten Deutschlands ergab, dass rund 16 % der Erwachsenen nach dem Kriterium der Weltgesundheitsorganisation (WHO) schwerhörig sind. Die Belastbarkeit landesweiter Hochrechnungen aus regional durchgeführten epidemiologischen Untersuchungen kann indes infrage gestellt werden.

Methoden

Die Studie „Wie hört Deutschland?" wurde unabhängig von HÖRSTAT im südwestdeutschen Aalen durchgeführt. Beide Querschnittstudien basierten auf stratifizierten Zufallsstichproben aus der Allgemeinbevölkerung. Der mittlere Tonhörverlust bei 500 Hz, 1, 2 und 4 kHz („pure-tone average", PTA4), die Prävalenz von Schwerhörigkeit (WHO-Kriterium: PTA4 des besseren Ohrs >25 dB HL) und die Versorgung mit Hörgeräten wurden verglichen. Die Daten aus Aalen und HÖRSTAT wurden zusammengeführt (n = 3105), um die Prävalenz von Schwerhörigkeit in ihrer graduellen Ausprägung für die Jahre 2015, 2020 und 2025 hochzurechnen.

Ergebnisse

Die beobachteten mittleren Hörverluste beider Studien stimmen sehr gut überein. Gewichtet nach Maßgabe der Bevölkerungsstatistik sind 16,2 % der Erwachsenen in Deutschland (11,1 Mio.) nach dem WHO-Kriterium schwerhörig. Aufgrund der demographischen Entwicklung ist mittelfristig ein Prävalenzanstieg von 1 % pro Jahrfünft zu erwarten. Bei vergleichbarem Hörverlust ist die Versorgung mit Hörgeräten in den Studienorten unterschiedlich.

Schlussfolgerung

Bei Adjustierung der Geschlechts- und Altersverteilung auf die europäische Standardpopulation (ESP) liegt die Prävalenz von Schwerhörigkeit in HÖRSTAT ebenso wie in der Aalener Untersuchung deutlich niedriger als in internationalen Vergleichsstudien. Die Analyse basiert ausschließlich auf Querschnittsdaten. Mögliche Kohorteneffekte sind in der Vorausberechnung der Prävalenz deshalb nicht berücksichtigt.

http://ift.tt/2mhdckK

Wahrnehmung von Hörproblemen bei älteren Menschen

Zusammenfassung

Hintergrund

Altersschwerhörigkeit ist eine der häufigsten chronisch-sensorischen Beeinträchtigungen in der älteren Bevölkerungsgruppe und wird verbunden mit Reduktion von kognitiven Fähigkeiten, Depression, Rückzug, Isolation und geringerem Wohlbefinden.

Ziele

Das erste Ziel war, die Selbsteinschätzung des Hörhandicaps von älteren Frauen und Männern mit Altersschwerhörigkeit (≥55 Jahre) zu erfassen sowie den Zusammenhang zwischen Hörverlust und wahrgenommenen Hörproblemen zu untersuchen. Das zweite Ziel war eine tiefgehende Auseinandersetzung mit den subjektiven Erfahrungen in Bezug auf die Folgen von Schwerhörigkeit im Alltag.

Methode

Im quantitativen Teil wurden im Zuge der schriftlichen Befragung Daten von 65 Altersschwerhörigen in Österreich gesammelt. Hierfür wurde das Instrument Hearing Handicap Inventory for the Elderly (HHIE) herangezogen. Im qualitativen Teil erfolgten problemzentrierte Interviews zur Erfassung der Erfahrungen mit Schwerhörigkeit und die Datenanalyse von weiteren 14 altersschwerhörigen Menschen.

Ergebnisse

Teilnehmende stuften ihr Hörhandicap im Durchschnitt als leichtgradig ein und nahmen Folgen auf der emotionalen und sozialen sowie Kommunikationsebene wahr. Darüber hinaus konnten Unsicherheitsgefühle identifiziert werden. Zudem weisen die Ergebnisse auf einen Zusammenhang sowie auf eine Diskrepanz zwischen Hörverlust und Hörhandicap hin; nicht alle Teilnehmenden nahmen ein Hörhandicap wahr.

Schlussfolgerung

Eine patientenzentrierte Behandlung, in der (1) objektive und subjektive Instrumente zur Erfassung von Hörproblemen zur Anwendung kommen, (2) nahestehende Personen einbezogen werden, (3) Aufklärung und Informationsaustausch stattfindet und (4) eine gemeinsame Entscheidung gefunden wird, könnte die Lebensqualität und Versorgungsqualität verbessern.

http://ift.tt/2mDUvdF

Update HNO

http://ift.tt/2mDAsMl

Acute vestibular syndrome in cerebellar stroke

Abstract

The current paper reports on a patient with recurrent rotational vertigo and persistent dizziness and imbalance lasting several weeks, who underwent extensive neuro-otological and radiological examinations. Pathological findings initially included right-sided benign paroxysmal positional vertigo (BPPV), persistent horizontal spontaneous nystagmus (SPN) to the left, and a pathological bedside and video head impulse test (HIT) on the left. The pathological HIT on the left and the SPN to the left indicated a central origin. Therefore, cranial magnetic resonance imaging was performed which revealed a left-sided ischemic stroke in the territory of the medial branch of the posterior inferior cerebellar artery (mPICA).

http://ift.tt/2mhdl7S

Intraoperative Funktionsüberwachung des N. facialis

Zusammenfassung

Hintergrund

Fragestellung

Welche Methoden zur intraoperativen Funktionsüberwachung haben sich entwickelt? Welche Methoden sind aktuell in Gebrauch, und welche Ziele können damit sinnvoll verfolgt werden?

Material und Methoden

Auswertung und Zusammenfassung der Literatur, Diskussion der vorhandenen Methoden und ihrer Fähigkeiten, die gesteckten Ziele zu erreichen.

Ergebnisse

Schlussfolgerungen

http://ift.tt/2mDLEc9

Mobile tablet audiometry in fluctuating autoimmune ear disease

Abstract

Background

Methods

Results

Conclusion

http://ift.tt/2lW8A1T

Prävalenz von Schwerhörigkeit in Nord- und Süddeutschland

Zusammenfassung

Hintergrund

Methoden

Ergebnisse

Schlussfolgerung

http://ift.tt/2mhdckK

Wahrnehmung von Hörproblemen bei älteren Menschen

Zusammenfassung

Hintergrund

Ziele

Methode

Ergebnisse

Schlussfolgerung

http://ift.tt/2mDUvdF

Acute vestibular syndrome in cerebellar stroke

Abstract

http://ift.tt/2mhdl7S

Update HNO

http://ift.tt/2mDAsMl

Effect of groups at α-position and side-chain structure of comonomers on surface free energy and surface reorganization of fluorinated methacrylate copolymer

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Zixu Gu, Jun Cheng, Mingzu Zhang, Jinlin He, Peihong Ni
Surface free energy and surface reorganization, two essential properties for low surface free energy materials, have been researched by studying the effects of the groups (H or CH3) at α-position and the side-chain structures (flexible or rigid) of alkyl (meth)acrylate on a series of fluorinated copolymers poly (perfluorohexylethyl methacrylate)-co-poly [alkyl (meth)acrylate]. The static contact angle, X-ray photoelectron spectroscopy (XPS), and surface tension studies indicate that both the groups at α-position and the side-chain structures of alkyl (meth)acrylate can significantly influence the arrangement of perfluoroalkyl chains at the interface, resulting in different fluorine-enriched concentrations on the interface, which will finally affect the surface free energy of the copolymer. The dynamic contact angle measurement shows that the surface reorganization of the fluorinated chains are directly associated with the Tg of these copolymers, and decrease with the increasing Tg. All these results show that the copolymers containing H at the α-position and flexible side-chain in comonomer have lower surface free energy and higher surface reorganization, while the steric hindrance effects of α-methyl groups and/or rigid side-chain in comonomer allow the copolymers having higher surface free energy and lower surface reorganization.

Graphical abstract

http://ift.tt/2mVPPk7

Development of structure–property relationships that allow independent control of glass transition temperature, melting temperature, and rheology in a library of bio-based succinate polyester polyols

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Alan K. Schrock, Heather S.C. Hamilton, Baylen D. Thompson, Kenneth Ulrich, Cathlene del Rosario, Carl Jacky Saint-Louis, William D. Coggio
A library of 20 bio-based succinate (SA) diol, co-diol, and co-diacid polyester polyols (PESPs) was generated and characterized, giving detailed understanding for tuning of their thermal transitions and rheological parameters. SA and 1,3-propanediol, 1,4-butanediol (BDO), 1,6-hexanediol, 2,2-dimethyl-1,3-propanediol, 3-methyl-1,5-pentanediol, diethylene glycol (DEG), adipic acid, or sebacic acid, and the blended diols were oligomerized to 1000 and 2000 Da Mn. The SA PESP melting point and its ability to crystallize can be set by controlling the structures and ratios of co-diols or co-diacids. We also show that the PESPs follow the expected Arrhenius temperature–viscosity relationship, but with a clear break in activation energy between PESPs with and without pendent methyl substituents and with DEG. PESP glass transition temperature, melting points, and rheology can be controlled independently by use of co-monomers with and without pendent methyl groups and with DEG.

Graphical abstract

http://ift.tt/2mVN1TU

Editorial board

Publication date: 10 March 2017
Source:Polymer, Volume 112

http://ift.tt/2mVPeP5

Carbon nanotube induced double percolation in polymer blends: Morphology, rheology and broadband dielectric properties

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Ivonne Otero-Navas, Mohammad Arjmand, Uttandaraman Sundararaj
In this study, we investigate the effect of multi-walled carbon nanotube (MWCNT) on the rheology, morphology and broadband dielectric properties of polypropylene:polystyrene (PP:PS) blends (PP:PS—10:90, 50:50 and 90:10). Transmission electron microscopy showed that MWCNTs were localized at the interface and inside the PS phase, regardless of the polymer blend ratio. Employing scanning electron microscopy, we observed that addition of MWCNT led to a transition from dispersed to interconnected morphology for the blends with PS as minor phase (PP:PS/50:50 and PP:PS/90:10). We propose that the selective localization of MWCNT in PS and at the interface slowed down the breakup mechanisms, increasing the lifetime of PS/MWCNT elongated domains, thus decreasing the amount of PS/MWCNT needed to percolate in PP phase. In addition, it is proposed that MWCNT located at the interface act as bridges between PS/MWCNT domains, favouring the coarsening of PS/MWCNT domains. The dielectric properties of the polymer blends PP:PS/50:50 and PP:PS/90:10 confirmed that double percolation was achieved with increase in MWCNT content. This transition provided the possibility to tune dielectric properties of the PP:PS/MWCNT blends. The double percolated structure offered high imaginary permittivity, while the dispersed morphology presented low imaginary permittivity. In other words, this study reveals that manipulating blend morphology can lead to blends with capacitive or dissipative characteristics.

Graphical abstract

http://ift.tt/2m0xkqv

Poly(2,6-dimethyl-1,4-phenylene oxide) blends with a poly(arylene ether ketone) for gas separation membranes

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Andrew Shaver, Joshua D. Moon, Donald Savacool, Wenrui Zhang, Gurtej Narang, Gregory Miller, Britannia Vondrasek, J.J. Lesko, Benny D. Freeman, J.S. Riffle, James E. McGrath
Poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) is utilized for gas separation membranes. It has a relatively high free volume with high gas permeabilities but suffers from low selectivities. PPO polymers with Mn's from 2000 to 22,000 g/mole were synthesized and blended with a poly(arylene ether ketone) derived from bisphenol A and difluorobenzophenone (BPA-PAEK). DSC showed that the blends with all but the lowest molecular weight PPO had two Tg's, thus suggesting that two phases were present. The ketone carbon and benzylic methyl groups on the BPA-PAEK and the PPO polymers crosslinked upon exposure to UV light. The gel fractions after UV exposure were high and the tensile properties were similar to the PPO control polymer that is currently used as a gas separation membrane. The crosslinked blends had improved gas selectivities over their linear counterparts. The 90/10 wt/wt 22k PPO/BPA PAEK crosslinked blends gained the most O2/N2 selectivity and maintained a high permeability.

Graphical abstract

http://ift.tt/2m0pv4d

Graphical Contents list & Author index

Publication date: 10 March 2017
Source:Polymer, Volume 112

http://ift.tt/2m0Gvae

The first fossil Platyrrhini (Primates: Anthropoidea) from Venezuela: A capuchin monkey from the Plio-Pleistocene of El Breal de Orocual

Publication date: Available online 6 March 2017
Source:Journal of Human Evolution
Author(s): Damián Ruiz-Ramoni, Ascanio D. Rincón, Andrés Solórzano, Salvador Moyà-Solà

http://ift.tt/2m0v3vr

Antidiabetic medication adherence and associated factors among patients in Botswana; implications for the future

Publication date: Available online 6 March 2017
Source:Alexandria Journal of Medicine
Author(s): Godfrey Mutashambara Rwegerera, Thato Moshomo, Marea Gaenamong, Taibat Aderonke Oyewo, Sivasomnath Gollakota, Francis Apolinary Mhimbira, Joseph Fadare, Brian Godman, Johanna C. Meyer, Yordanka Piña Rivera
BackgroundDiabetes mellitus (DM) is a major global public health problem. Lack of adherence to medication causes suboptimal glycemic control increasing complication rates, costs and mortality. The objective of the study was to determine current antidiabetic medication adherence in Botswana and assess associated factors so as to direct potential future interventions.Materials and methodsA cross-sectional study among 376 randomly selected diabetic patients attending a leading clinic in Gaborone, Botswana. Eight item Morisky Medication adherence questionnaire was used to assess antidiabetic medication adherence. A structured questionnaire was also used to collect information on factors influencing adherence including age, gender, education, type and duration of diabetes, treatment, complications and HIV status. Data were entered and analyzed using STATA Version 14, and logistic regression performed.ResultsOver forty percent (41.8%) of patients were non-adherent to antidiabetic medications. Studied sociodemographic characteristics and clinical variables did not affect adherence. HIV positive status was associated with a statistically significant better adherence at multivariate analysis.ConclusionAdherence to antidiabetic medication was found to be suboptimal in a setting where medicines are provided free of charge. Only HIV positivity was found to be significantly associated with better adherence, probably due to effect of greater psychosocial support and counselling as part of HIV treatment. There is a need to carry out studies to further improve understanding of factors associated with medication adherence that are pertinent to Botswana and similar settings given the growing prevalence of diabetes.

http://ift.tt/2mzjrmj

IGF-I and IGFBP-3 levels and their correlations with carcinoembryonic antigen in colorectal cancer patients

Publication date: Available online 7 March 2017
Source:Alexandria Journal of Medicine
Author(s): Çiğdem Yağcıoğlu Yücel, Gönül Erden, Fatma Meriç Yılmaz, Sevilay Sezer, Esin Çalcı
BackgroundColorectal cancer is one of the most frequently seen cancers worldwide. Currently, CEA is the most commonly used tumor marker in colorectal cancer. The changes in IGF/IGFBP equilibrium is also known to cause carcinogenesis. In this study, we aimed to monitor IGF-I/IGFBP-3 levels, the changes in IGF-I/IGFBP-3 ratio and correlations of these peptides with the common tumor marker CEA.Materials and methods55 colorectal cancer patients and 35 control group patients were included in this study. Serum CEA, IGF-I and IGFBP-3 levels of all specimens were measured with chemiluminescence method.ResultsIn colorectal cancer patients, IGF-I levels was found to be increased, IGFBP-3 levels decreased and IGF-I/IGFBP-3 ratio was increased; when compared to control group (p<0.05). A moderately significant correlation was found between the conventional tumor marker CEA and IGF-I and IGF-BP3 (p=0.001, r=0.533 and p=0.001, r=−0.573 respectively).ConclusionsIGF-I/IGFBP-3 ratio seems to be increased in the colorectal cancer patients. When considered with the moderate correlation levels of these peptides with CEA, this increase in IGF-I/IGF-BP3 ratio may be useful in monitoring carcinogenesis in colorectal cancer patients among with CEA but more detailed and extensive studies in larger study groups needed to be carried out.

http://ift.tt/2ncBueS

Promoting global action on hearing loss: World hearing day.

Promoting global action on hearing loss: World hearing day.

Int J Audiol. 2017 Mar;56(3):145-147

Authors: Chadha S, Cieza A

PMID: 28262049 [PubMed - in process]

http://ift.tt/2m0pPQv

Promoting global action on hearing loss: World hearing day.

Promoting global action on hearing loss: World hearing day.

Int J Audiol. 2017 Mar;56(3):145-147

Authors: Chadha S, Cieza A

PMID: 28262049 [PubMed - in process]

http://ift.tt/2m0pPQv

Glutamine dipeptide and cortisol change the liver glucose metabolism and reduce the severity of insulin-induced hypoglycaemia in untreated T1DM Swiss mice.

Glutamine dipeptide and cortisol change the liver glucose metabolism and reduce the severity of insulin-induced hypoglycaemia in untreated T1DM Swiss mice.

Arch Physiol Biochem. 2017 May;123(2):134-144

Authors: Bataglini C, Rezende DG, Primo MA, Gomes CR, Pedrosa MM, Godoi VA

Abstract
CONTEXT: Glutamine is conditionally essential in type 1 diabetes mellitus, and might be useful to counteract hypoglycaemia.
OBJECTIVE: To investigate the systemic and hepatic effects of counter-regulatory hormones and glutamine dipeptide (GDP) during hypoglycemic episodes.
MATERIALS AND METHODS: Diabetic Swiss mice made hypoglycaemic by insulin injection (1 U/kg) were given counter-regulatory hormones and/or GDP. Sixty minutes later, liver histology, liver glucose metabolism and plasma were assessed.
RESULTS: Combined, cortisol and GDP improved the hypoglycemic profile. During liver perfusion, gluconeogenesis was possibly the major pathway leading to glucose release. Perfusion with gluconeogenic precursors after glycogen depletion by adrenaline increased liver glucose and urea release.
DISCUSSION: The less severe hypoglycaemia could result from cortisol stimulating periportal gluconeogenesis and GDP inhibiting pericentral glycogenolysis, both favouring liver glucose release.
CONCLUSIONS: At least some benefits of GDP and cortisol during hypoglycaemia came from their hepatic actions, and their use in diabetic patients should be explored.

PMID: 28263096 [PubMed - in process]

http://ift.tt/2lBUAPy

Comparing pre-therapeutic 124 I and 131 I uptake tests with intra-therapeutic 131 I uptake in benign thyroid disorders

Abstract

Purpose

¹²⁴I-PET/CT can be used for pre-therapeutic assessment of radioactive iodine uptake in benign thyroid disorders, however systematic comparisons with intra-therapeutic uptake are still lacking for these disorders. The goals of this study were to compare ¹²⁴I RAIU and conventional ¹³¹I RAIU tests with each other; to compare both tests with intra-therapeutic uptake (reference); and to verify the time course of radioactive iodine uptake at three time points (30, 102, and 336 h [14 days] post administration; p.a.).

Methods

Thirteen patients with benign thyroid diseases underwent ¹³¹I RAIU test and ¹²⁴I RAIU test one after another before the intra-therapeutic ¹³¹I uptake (reference) was measured via short-range and long-range measurements. After correction for decay, relative uptake differences were calculated and subjected to the Bland-Altman method for the evaluation of levels of agreement.

Results

Radioactive iodine uptake tests with ¹²⁴I-PET/CT and ¹³¹I probe did not show systematic deviations at any time point. Likewise, at 30 and 102 h p.a. there was no systematic discrepancy between pre-therapeutic and intra-therapeutic uptake levels. At 14 days p.a., however, both pre-therapeutic tests tended to overestimate the uptake compared to reference. Findings showed, for the first time with ¹²⁴I, that radioiodine therapy has some early radiobiological effects possibly limiting the accuracy of pre-therapeutic dosimetry.

Conclusions

¹²⁴I RAIU tests represent a feasible alternative to standard ¹³¹I RAIU tests. The additional benefits of ¹²⁴I-PET/CT (e.g., functional topography, inclusion of retrosternal areas, possibility to enable fusion imaging) may thus increase the scope of this technology in benign thyroid disorders.

http://ift.tt/2lYWwOb

Intestinal absorption and buccal absorption of liquid levothyroxine

http://ift.tt/2lACoWv

Paired suicide in a young refugee couple on the Thai-Myanmar border

Gracia Fellmeth Sep 15, 2016; 2016:bcr2016215527-bcr2016215527 case-report

http://ift.tt/2ncauMz

Anabolic androgen use in the management of hereditary angioedema

Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare, life-threatening disease that imposes a significant burden on affected patients. 17α-alkylated androgens (anabolic androgens) decrease attack frequency and severity but carry the risk of potentially serious dose-related adverse effects. Despite the emergence of targeted therapies for HAE, continued anabolic androgen use has been driven in part by their low cost.

http://ift.tt/2mgXw18

Survey of pediatric trainee knowledge: dose, concentration, and route of epinephrine

Epinephrine is the first medication listed in the American Heart Association's Pediatric Algorithm for Cardiac Arrest, and it is the primary medication in the treatment of anaphylaxis.1–3 It is frequently dosed and administered during stressful circumstances, and errors can result in poor patient outcomes. Epinephrine knowledge deficits are known to occur, but their prevalence in pediatric trainees is unclear.4,5 We distributed a survey of 8 test questions (Table 1) to assess knowledge gaps related to inpatient and outpatient epinephrine usage.

http://ift.tt/2mDaqsE

Sex differences in the efficacy, safety, and tolerability of omalizumab after 1 year in Maltese patients with asthma

Omalizumab has been proven to be a safe and effective drug1 in patients with severe, persistent, allergic IgE-mediated asthma. Sex differences in asthma prevalence and severity, including IgE-mediated allergic asthma, have been recognized, with women said to be more severely affected.2,3 Studies have identified that men and women respond differently to their asthma when comparing hospital admissions, quality of life, and use of inhalers.4 It is also postulated that responses to antiasthmatic drugs differ.

http://ift.tt/2mh4PWB

Anabolic androgen use in the management of hereditary angioedema

Survey of pediatric trainee knowledge: dose, concentration, and route of epinephrine

Sex differences in the efficacy, safety, and tolerability of omalizumab after 1 year in Maltese patients with asthma

Migraine – a look down the nose

Studies have suggested that contact between opposing mucosal surfaces in the nasal wall and cavity can be a target of the surgical treatment of migraines. Unfortunately, not enough is known about the role of nasal pathology in the pathogenesis of this condition. The co-existence of further rhinological disorders can be an impediment in defining the cause and effect of anatomical variants. The authors compared MRI scans of migraine- and non-migraine patients to determine the prevalence of such mucosal contact points in an effort to extrapolate whether there is a significant association with migraines.

http://ift.tt/2mDqKK8

A rare presentation of myxofibrosarcoma as a Pancoast tumor: a case report

Myxofibrosarcoma is an aggressive soft tissue neoplasm, classified as a variant of malignant fibrous histiocytoma. Most often, it occurs in middle to late adult life peaking in the seventh decade and involving...

http://ift.tt/2m04MNY

A STAT1-gain-of-function mutation causing Th17 deficiency with chronic mucocutaneous candidiasis, psoriasiform hyperkeratosis and dermatophytosis

Jakob Nielsen Oct 22, 2015; 2015:bcr2015211372-bcr2015211372 case-report

http://ift.tt/2mjLMMX

Large retroperitoneal low-grade extraskeletal osteosarcoma

Jiten Jaipuria Mar 22, 2014; 2014:bcr-2014-203745-bcr-2014-203745 case-report

http://ift.tt/2ncmtd0

Eosinophilic enteritis: a rare cause of diarrhoea

Ana Lladó
Sep 30, 2013; 2013:bcr2013201125-bcr2013201125
case-report

http://ift.tt/2mjLFki

Acute kidney injury requiring haemodialysis following ingestion of mephedrone

Rhys Rhidian Mar 1, 2013; 2013:bcr2012007974-bcr2012007974 case-report

http://ift.tt/2nchcT6

Cirrhosis, cellulitis and cats: a 'purrfect' combination for life-threatening spontaneous bacterial peritonitis from Pasteurella multocida

Penelope Hey Nov 12, 2012; 2012:bcr2012007397-bcr2012007397 case-report

http://ift.tt/2mk7pwz

Efficacy and cost of micronutrient treatment of childhood psychosis

Megan Rodway Nov 9, 2012; 2012:bcr2012007213-bcr2012007213 case-report

http://ift.tt/2nc3xLA

A microbiological hazard of rural living: Clostridium septicum brain abscess in a child with E coli 0157 associated haemolytic uraemic syndrome

Eleri J Williams Jun 26, 2012; 2012:bcr2012006424-bcr2012006424 case-report

http://ift.tt/2mjz4hg

Management of metastatic castration-resistant prostate cancer: a focus on radium-223

Publication date: Available online 6 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sergio Baldari, Giuseppe Boni, Roberto Bortolus, Orazio Caffo, Giario Conti, Giuseppe De Vincentis, Fabio Monari, Giuseppe Procopio, Daniele Santini, Ettore Seregni, Riccardo Valdagni
Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease. An expert multidisciplinary panel convened in Milan, Italy to review the current best-evidence literature on radium-223 and to convey their personal expertise with the use of radium-223 and identify possible strategies for best practice. This article summarizes the best available evidence for the use of radium-223, discusses the essential role of the multidisciplinary team in delivering effective treatment for mCRPC, clarifies pre- and post-treatment evaluation and monitoring, and outlines future scenarios for radium-223 in the treatment of men with MCRPC.

http://ift.tt/2mz8Ibg

Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality Autonomic Imbalance Predicts CVD, DM, Mortality

The Journal of Clinical Endocrinology &Metabolism, Early Release.

http://ift.tt/2nc5ZBF

WITHDRAWN: Eligibility for Statin Therapy According to New Cholesterol Guidelines on Primary Aldosteronism

The Journal of Clinical Endocrinology &Metabolism, Early Release.

http://ift.tt/2mz4tNe

WITHDRAWN: High Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels (article published in final form as 10.1210/jc.2015-1966)

The Journal of Clinical Endocrinology &Metabolism, Early Release.

http://ift.tt/2ncdaKl

WITHDRAWN: Low-density lipoprotein cholesterol is associated with fracture risk in diabetes patients – a nested case-control study

The Journal of Clinical Endocrinology &Metabolism, Early Release.

http://ift.tt/2mzclhE

A rare presentation of myxofibrosarcoma as a Pancoast tumor: a case report

MRI of the Digital Nerves of the Hand: Anatomy and Spectrum of Pathology

Publication date: Available online 6 March 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Charles H. Mitchell, Laura M. Fayad, Shivani Ahlawat
Digital nerves are intrinsic to the sensory and motor function of the hand. These nerves represent the terminal ramifications of the ulnar, median and radial nerves and are located distal to the carpal tunnel and Guyon′s canal. With magnetic resonance imaging (MRI), traumatic and non-traumatic abnormalities of the digital nerves can be shown with high contrast as well as high spatial resolution. Digital nerve abnormalities are most commonly post-traumatic in nature; however, infection, inflammatory, vascular malformations and neoplasms can rarely occur. MRI is playing an increasing role in the assessment of peripheral nerve injury throughout the body, and in the hand, can accurately identify the extent and character of digital nerve abnormalities prior to operative intervention.

http://ift.tt/2mVg75O

Protochlamydia phocaeensis sp. nov., a new Chlamydiales species with host dependent replication cycle

Publication date: Available online 7 March 2017
Source:Microbes and Infection
Author(s): Jacques Y. Bou Khalil, Samia Benamar, Fabrizio Di Pinto, Caroline Blanc-Tailleur, Didier Raoult, Bernard La Scola
Chlamydiae are pathogenic and symbiotic bacteria, which form an important part of amoeba-associated microorganisms. In this paper, we report the isolation, developmental cycle and genome analysis of Protochlamydia phocaeensis sp. nov., an obligate intracellular parasite with a large host spectrum, able to infect Acanthamoeba castellanii, Acanthamoeba polyphaga, and Vermamoeba vermiformis. The genome size is 3,424,182 bp with a GC content of 42 %. This bacterium displayed a particular developmental cycle depending on the infected host. The P. phocaeensis showed typical inclusion vacuoles in A. castellanii, while these were absent in Vermamoeba. vermiformis. Since "Chlamydiae – amoebae" interactions are supposed to depend on the chlamydial species, our findings speculate that variations in the developmental cycle of certain Chlamydiae is also host dependent.

http://ift.tt/2myX9RD

Cerebellar compartmentation of prion pathogenesis

Abstract

In prion diseases, the brain lesion profile is influenced by the prion "strain" properties, the invasion route to the brain, and still unknown host cell-specific parameters. To gain insight into those endogenous factors, we analyzed the histopathological alterations induced by distinct prion strains in the mouse cerebellum. We show that 22L and ME7 scrapie prion proteins (PrP^22L, PrP^ME7), but not bovine spongiform encephalopathy PrP^6PB1, accumulate in a reproducible parasagittal banding pattern in the cerebellar cortex of infected mice. Such banding pattern of PrP^22L aggregation did not depend on the neuroinvasion route, but coincided with the parasagittal compartmentation of the cerebellum mostly defined by the expression of zebrins, such as aldolase C and the excitatory amino acid transporter 4, in Purkinje cells. We provide evidence that Purkinje cells display a differential, subtype-specific vulnerability to 22L prions with zebrin-expressing Purkinje cells being more resistant to prion toxicity, while in stripes where PrP^22L accumulated most zebrin-deficient Purkinje cells are lost and spongiosis accentuated. In addition, in PrP^22L stripes, enhanced reactive astrocyte processes associated with microglia activation support interdependent events between the topographic pattern of Purkinje cell death, reactive gliosis and PrP^22L accumulation. Finally, we find that in preclinically-ill mice prion infection promotes at the membrane of astrocytes enveloping Purkinje cell excitatory synapses, upregulation of tumor necrosis factor-α receptor type 1 (TNFR1), a key mediator of the neuroinflammation process. These overall data show that Purkinje cell sensitivity to prion insult is locally restricted by the parasagittal compartmentation of the cerebellum, and that perisynaptic astrocytes may contribute to prion pathogenesis through prion-induced TNFR1 upregulation. This article is protected by copyright. All rights reserved.

http://ift.tt/2n3yfYc

Fatal anaphylaxis in France: analysis of national anaphylaxis data, 1979-2011

Urban Residence, Neighborhood Poverty, race/ethnicity and Asthma Morbidity Among Children in Medicaid

Circulating Gluten-Specific FOXP3+CD39+ Regulatory T Cells Have Impaired Suppressive Function in Celiac Disease

We performed a novel study of gluten-specific FOXP3+ Tregs in patients with celiac disease and found that, although these cells comprise the majority of circulating gluten-specific CD4+ T-cells, they have impaired suppressive function.

http://ift.tt/2mgMRn0

Transcription Factor T-bet Orchestrates Lineage Development and Function in the Immune System

Publication date: Available online 7 March 2017
Source:Trends in Immunology
Author(s): Axel Kallies, Kim L. Good-Jacobson
T-bet was originally described as the key transcription factor defining type 1 T helper (Th) cells. However, it is now clear that it drives the orchestrated generation of effector and memory cells in multiple different lymphocyte lineages. In addition to Th1 cells, CD8 T cells, B cells and some innate lymphocyte populations require T-bet for their development or differentiation in response to antigen. Furthermore, other Th cell populations, including T follicular helper and Th17, as well as regulatory T cells can co-opt T-bet expression to promote functional diversification and colocalization. Thus, T-bet broadly regulates transcriptional programs in response to type 1 inflammatory signals and mediates the coordinated differentiation, function, migration and survival of effector and memory lymphocyte subsets in the affected tissue. Therefore, T-bet expression is essential for effective clearance of pathogens and maintenance of immunity.

http://ift.tt/2mgEEz2

The S(c)ensory Immune System Theory

Publication date: Available online 7 March 2017
Source:Trends in Immunology
Author(s): Henrique Veiga-Fernandes, António A. Freitas
Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms. This context determined the emergence of the 'sensory immune system', which operates in a s(c)ensor mode to ensure systems physiology, organismic homeostasis, and perpetuation of its replicating molecules.

http://ift.tt/2mV8Seq

The effect of caffeic acid phenethyl ester and thymoquinone on otitis media with effusion in rats

In this study, we aimed to investigate the effect of CAPE and thymoquinone in experimental rat otitis media with effusion (OME) model.

http://ift.tt/2mzaf15

Tracheal Tear from Blunt Neck Trauma in Children: Diagnosis and Management

We describe the management of posterior trachea tears after blunt neck trauma in two children. The first, a 5 year-old boy who fell off his scooter, causing a 1.0cm tear in the membranous cervical trachea, was managed conservatively with 5 days of intubation. The second, a 12 year-old girl who fell on her bicycle, causing a 4.0cm tear in the membranous thoracic trachea, was repaired with thoracoscopic techniques. The presumed mechanism may be expansion of the U-shaped cartilage with tear of the membranous trachea.

http://ift.tt/2n3tGNg

Velopharyngeal insufficiency managed by autologous fat grafting in patients with aberrant courses of internal carotid arteries

Velopharyngeal insufficiency (VPI) is usually managed, besides speech therapy, by performing a velopharyngoplasty. An alternate approach is autologous fat grafting (AFG) of the posterior pharyngeal wall. About 5% of the population has internal carotid arteries (ICA) with an aberrant course. This anatomic variation can be responsible for surgical difficulties while when performing a velopharyngoplasty, and therefore lead surgeons to only consider a speech reeducation of VPI. However, AFG is does not bear such surgical morbidity.

http://ift.tt/2mz1Lau

Dynamin-Related Protein 1-Dependent Mitochondrial Fission Changes in the Dorsal Vagal Complex Regulate Insulin Action

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Beatrice M. Filippi, Mona A. Abraham, Pamuditha N. Silva, Mozhgan Rasti, Mary P. LaPierre, Paige V. Bauer, Jonathan V. Rocheleau, Tony K.T. Lam
Mitochondria undergo dynamic changes to maintain function in eukaryotic cells. Insulin action in parallel regulates glucose homeostasis, but whether specific changes in mitochondrial dynamics alter insulin action and glucose homeostasis remains elusive. Here, we report that high-fat feeding in rodents incurred adaptive dynamic changes in mitochondria through an increase in mitochondrial fission in parallel to an activation of dynamin-related protein 1 (Drp1) in the dorsal vagal complex (DVC) of the brain. Direct inhibition of Drp1 negated high-fat-feeding-induced mitochondrial fission, endoplasmic reticulum (ER) stress, and insulin resistance in the DVC and subsequently restored hepatic glucose production regulation. Conversely, molecular activation of DVC Drp1 in healthy rodents was sufficient to induce DVC mitochondrial fission, ER stress, and insulin resistance. Together, these data illustrate that Drp1-dependent mitochondrial fission changes in the DVC regulate insulin action and suggest that targeting the Drp1-mitochondrial-dependent pathway in the brain may have therapeutic potential in insulin resistance.

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Filippi et al. find that induction of Drp1-dependent mitochondrial fission in the dorsal vagal complex of rodents under high-fat feeding can induce ER stress and insulin resistance.

http://ift.tt/2lVeyQu

Mutations that Allow SIR2 Orthologs to Function in a NAD+-Depleted Environment

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Caitlin R. Ondracek, Vincent Frappier, Alison E. Ringel, Cynthia Wolberger, Leonard Guarente
Sirtuin enzymes depend on NAD⁺ to catalyze protein deacetylation. Therefore, the lowering of NAD⁺ during aging leads to decreased sirtuin activity and may speed up aging processes in laboratory animals and humans. In this study, we used a genetic screen to identify two mutations in the catalytic domain of yeast Sir2 that allow the enzyme to function in an NAD⁺-depleted environment. These mutant enzymes give rise to a significant increase of yeast replicative lifespan and increase deacetylation by the Sir2 ortholog, SIRT1, in mammalian cells. Our data suggest that these mutations increase the stability of the conserved catalytic sirtuin domain, thereby increasing the catalytic efficiency of the mutant enzymes. Our approach to identifying sirtuin mutants that permit function in NAD⁺-limited environments may inform the design of small molecules that can maintain sirtuin activity in aging organisms.

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Ondracek et al. report the identification of two adaptive mutations in yeast Sir2 that allow the enzyme to function in an NAD⁺-depleted environment by enhancing protein stability and increasing enzyme catalysis, which increases yeast replicative lifespan and deacetylation of in vivo substrates by the Sir2 ortholog, SIRT1, in mammalian cells.

http://ift.tt/2lV3rHj

R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Floriane Lacour, Elsa Vezin, C. Florian Bentzinger, Marie-Claude Sincennes, Lorenzo Giordani, Arnaud Ferry, Robert Mitchell, Ketan Patel, Michael A. Rudnicki, Marie-Christine Chaboissier, Anne-Amandine Chassot, Fabien Le Grand
Wnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo) family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes. Furthermore, muscle cells lacking Rspo1 have a fusion phenotype leading to larger myotubes containing supernumerary nuclei both in vitro and in vivo. The increase in muscle fusion was dependent on downregulation of Wnt/β-catenin and upregulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that reciprocal control of antagonistic Wnt signaling pathways by Rspo1 in muscle stem cell progeny is a key step ensuring normal tissue architecture restoration following acute damage.

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Using mice lacking the Wnt enhancer Rspo1, Lacour et al. demonstrate that Rspo1 controls muscle cell fusion during skeletal muscle regeneration. Rspo1-null muscle progenitor cells differentiate less efficiently but fuse extensively compared to wild-type cells. Rspo1 is shown to regulate the antagonism between canonical and non-canonical Wnt signaling pathways.

http://ift.tt/2lVpwoZ

ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B. Krasieva, Sebastien de Feraudy, Bruce J. Tromberg, Sharon Huang, Chad P. Garner, Jie Wu, Dave S. Hoon, Anand K. Ganesan
Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune microenvironment to promote continued growth.

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Tumors grow not only because they acquire mutations that promote their growth but also because they prevent the immune system from recognizing them. Chen et al. identify ATR mutations in human melanoma tumors and determine that ATR mutant melanomas harness the immune system to accelerate tumor growth.

http://ift.tt/2lVe3pC

Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Mauricio Medrano, Laudine Communal, Kevin R. Brown, Marcin Iwanicki, Josee Normand, Joshua Paterson, Fabrice Sircoulomb, Paul Krzyzanowski, Marian Novak, Sasha A. Doodnauth, Fernando Suarez Saiz, Jane Cullis, Rima Al-awar, Benjamin G. Neel, John McPherson, Ronny Drapkin, Laurie Ailles, Anne-Marie Mes-Massons, Robert Rottapel
The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and comprehensive expression analysis of cell-surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. This study reveals cell-surface vulnerabilities associated with HGSC, provides a framework for identifying therapeutic targets, and reports a role for CD151 in HGSC.

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Teaser

Medrano et al. conduct whole-genome short hairpin RNA screens in 27 high-grade serous ovarian carcinoma (HGSC) cell lines to identify vulnerabilities in HGSC. Analysis of the cell surface reveals that CD151 is essential for cell survival through a ZEB-dependent mechanism.

http://ift.tt/2lV4uqQ

Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Melanie Paillard, György Csordás, Gergö Szanda, Tünde Golenár, Valentina Debattisti, Adam Bartok, Nadan Wang, Cynthia Moffat, Erin L. Seifert, András Spät, György Hajnóczky
Mitochondrial Ca²⁺ uptake through the Ca²⁺ uniporter supports cell functions, including oxidative metabolism, while meeting tissue-specific calcium signaling patterns and energy needs. The molecular mechanisms underlying tissue-specific control of the uniporter are unknown. Here, we investigated a possible role for tissue-specific stoichiometry between the Ca²⁺-sensing regulators (MICUs) and pore unit (MCU) of the uniporter. Low MICU1:MCU protein ratio lowered the [Ca²⁺] threshold for Ca²⁺ uptake and activation of oxidative metabolism but decreased the cooperativity of uniporter activation in heart and skeletal muscle compared to liver. In MICU1-overexpressing cells, MICU1 was pulled down by MCU proportionally to MICU1 overexpression, suggesting that MICU1:MCU protein ratio directly reflected their association. Overexpressing MICU1 in the heart increased MICU1:MCU ratio, leading to liver-like mitochondrial Ca²⁺ uptake phenotype and cardiac contractile dysfunction. Thus, the proportion of MICU1-free and MICU1-associated MCU controls these tissue-specific uniporter phenotypes and downstream Ca²⁺ tuning of oxidative metabolism.

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Teaser

Paillard et al. report that the relative abundance of the pore-forming protein of the mitochondrial Ca²⁺ uniporter (MCU) and its Ca²⁺-sensing regulator (MICU1) define the proportion of MCU complexes with or without MICU1. This ratio is central to programming tissue-specific mitochondrial Ca²⁺ uptake phenotypes in the heart and liver.

http://ift.tt/2lV82cq

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Koen M.A. Dreijerink, Anna C. Groner, Erica S.M. Vos, Alba Font-Tello, Lei Gu, David Chi, Jaime Reyes, Jennifer Cook, Elgene Lim, Charles Y. Lin, Wouter de Laat, Prakash K. Rao, Henry W. Long, Myles Brown
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER⁺ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.

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Teaser

Dreijerink et al. describe the oncogenic actions of the tumor suppressor menin in breast cancer cells. In mammary progenitor cells, menin regulates anti-proliferative genes. Menin is present at FOXA1 and GATA3-bound enhancers that associate with promoters through chromatin looping. Insight into menin's context-dependent function suggests therapeutic strategies.

http://ift.tt/2lV3piF

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τρίτη 7 Μαρτίου 2017

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