TLR9 played a more important role than TLR2 in the combination of maltose-binding protein and BCG-induced Th1 activation

Publication date: November 2016
Source:Molecular Immunology, Volume 79
Author(s): Weihua Ni, Fang Wang, Guomu Liu, Nannan Zhang, Hongyan Yuan, Jing Jie, Guixiang Tai
Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4⁺ T cells were stimulated with MBP and BCG in vitro. The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation. Results showed TLR2 antibody partly decreased MBP combined with BCG-induced IFN-γ production, MyD88 expression and IκB phosphorylation, indicating that TLR2-mediated MyD88-dependent pathway was involved in the MBP combined with BCG-induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88-dependent pathway played a more important role than TLR2 in the combination-induced Th1 activation. Further study showed that TLR9 inhibitor downregulated TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation collaboratively and our findings provided valuable information about designing more effective adjuvant for cancer therapy.



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Inducible costimulator (ICOS) potentiates TCR-induced calcium flux by augmenting PLCγ1 activation and actin remodeling

Publication date: November 2016
Source:Molecular Immunology, Volume 79
Author(s): Julien Leconte, Sahar Bagherzadeh Yazdchi, Vincent Panneton, Woong-Kyung Suh
The inducible costimulator (ICOS) is a T cell costimulatory receptor that plays crucial roles in T cell differentiation and function. So far, ICOS has been shown to activate three signaling components: phosphoinositide 3-kinase (PI3K), intracellular calcium mobilization, and TANK binding kinase 1 (TBK1). By generating a knock-in strain of mice in which the ICOS gene is modified such that the ICOS-mediated PI3K pathway is selectively abrogated while the capacity of ICOS to mobilize intracellular calcium remains intact, we have shown that ICOS-mediated PI3K activation is required for some but not all T cell responses. This suggests that the ICOS-calcium signaling axis may explain some of the PI3K-independent ICOS functions. Further, a recent in vivo imaging study indicated that ICOS-dependent intracellular calcium flux facilitates cognate T cell-B cell interactions within the germinal center. However, how ICOS promotes TCR-mediated calcium flux has not been clear. Here we identified a membrane proximal motif in the cytoplasmic tail of ICOS that is essential for ICOS-assisted calcium signaling and demonstrate that ICOS can induce calcium flux independently of other signaling motifs. We also provide evidence that ICOS potentiates phospholipase Cγ1 (PLCγ1) activation to enhance calcium release from the intracellular pool. In parallel, acute ligation of ICOS without TCR co-engagement leads to activation of small GTPases, RhoA and Cdc42, consistent with the capacity of ICOS to induce actin remodeling. Importantly, interruption of actin dynamics during acute TCR or TCR-ICOS co-ligation severely impairs calcium flux in T cells even in the presence of activated PLCγ1. Thus, ICOS potentiates TCR-induced calcium flux by enhancing PLCγ1 activation and actin remodeling in a coordinated manner.



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Relevance of carnosic acid to the treatment of several health disorders: Molecular targets and mechanisms

Publication date: December 2016
Source:Biomedicine & Pharmacotherapy, Volume 84
Author(s): Sana Bahri, Saloua Jameleddine, Vadim Shlyonsky
Carnosic acid is a phenolic diterperne compound found in abundance in sage and rosemary, which are both widely used in traditional medicine. Research over the past decade indicates that carnosic acid has multiple bioactive properties including antioxidant, anti-inflammatory and anticancer activities among others. This review summarizes the current in vitro and in vivo data about the efficacy of carnosic acid in the prevention or treatment of various experimental health disorders. The analysis of the literature allows an insight into the participation of numerous signaling pathways modulated by carnosic acid, into its synergistic potential and, thus, into the divergence in cellular mechanisms of action of this molecule.



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Differential role of microRNAs in prognosis, diagnosis, and therapy of ovarian cancer

Publication date: December 2016
Source:Biomedicine & Pharmacotherapy, Volume 84
Author(s): Ahmad Mahdian-shakib, Ruhollah Dorostkar, Mahdi Tat, Mohammad Sadegh Hashemzadeh, Navid Saidi
Ovarian cancer (OC) is the most lethal of malignant gynecological cancers, and has a very poor prognosis, frequently, attributable to late diagnosis and responsiveness to chemotherapy. In spite of the technological and medical approaches over the past four decades, involving the progression of several biological markers (mRNA and proteins biomarkers), the mortality rate of OC remains a challenge due to its late diagnosis, which is expressly ascribed to low specificities and sensitivities. Consequently, there is a crucial need for novel diagnostic and prognostic markers that can advance and initiate more individualized treatment, finally increasing survival of the patients. MiRNAs are non-coding RNAs that control target genes post transcriptionally. They are included in tumorigenesis, apoptosis, proliferation, invasion, metastasis, and chemoresistance. Several studies have within the last decade demonstrated that miRNAs are dysregulated in OC and have possibilities as diagnostic and prognostic biomarkers for OC. Additionally; recent studies have also focused on miRNAs as predictors of chemotherapy sensitivities and their potential as therapeutic targets. In this review, we discuss the current data involving the accumulating evidence of the altered expression of miRNAs in OC, their role in diagnosis, prognosis, and forecast of response to therapy. Given the heterogeneity of this disease, it is likely that advances in long-term survival might be also attained by translating the recent insights of miRNAs participation in OC into new targeted therapies that will have a crucial effect on the management of ovarian cancer.



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New potential phytotherapeutics obtained from white mulberry (Morus alba L.) leaves

Publication date: December 2016
Source:Biomedicine & Pharmacotherapy, Volume 84
Author(s): Anna Gryn-Rynko, Grzegorz Bazylak, Dorota Olszewska-Slonina
The present work demonstrates the profound and unique phyto-pharmacological and nutritional profile of white mulberry (Morus alba L.) leaves which containing considerable amounts of easy digestive proteins, carbohydrates, micro- and macronutrients, polyphenols, free amino acids, organic acids. The wide range of significant biopharmaceutical activities of the aqueous and polar organic solvents extracts from mulberry leaves – including antidiabetic, antibacterial, anticancer, cardiovascular, hypolipidemic, antioxidant, antiatherogenic, and anti-inflammatory – have been critically discussed. The main objective was to demonstrate the results of recently published study on the components of white mulberry leaves exhibiting their biological activity in the various pathological and health human ailments. In addition, we intend to drawn the attention of researchers and public health workers for the extended exploration of this deciduous plant leaves as the source of potential indigenous nutraceuticals and functional food products to enable development of alternative prevention and treatment protocols offered in therapy of the common non-communicable diseases and malignances.

Graphical abstract

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Real-time EEG Artifact Correction during fMRI using ICA

Publication date: Available online 30 September 2016
Source:Journal of Neuroscience Methods
Author(s): Ahmad Mayeli, Vadim Zotev, Hazem Refai, Jerzy Bodurka
BackgroundSimultaneous acquisition of EEG and fMRI data results in EEG signal contamination by imaging (MR) and ballistocardiogram (BCG) artifacts. Artifact correction of EEG data for real-time applications, such as neurofeedback studies, is the subject of ongoing research. To date, average artifact subtraction (AAS) is the most widespread real-time method used to partially remove BCG and imaging artifacts without requiring extra hardware equipment; no alternative software-only real time methods for removing EEG artifacts are available.New methodsWe introduce a novel, improved approach for real-time EEG artifact correction during fMRI (rtICA). The rtICA is based on real time independent component analysis (ICA) and it is employed following the AAS method. The rtICA was implemented and validated during EEG and fMRI experiments on healthy subjects.ResultsOur results demonstrate that the rtICA employed after the rtAAS can obtain 98.4% success in detection of eye blinks, 4.4 times larger INPS reductions compared to RecView-corrected data, and effectively reduce motion artifacts, as well as imaging and muscle artifacts, in real time on six healthy subjects.Comparison with existing methodsWe compared our real-time artifact reduction results with the rtAAS and various offline methods using multiple evaluation metrics, including power analysis. Importantly, the rtICA does not affect brain neuronal signals as reflected in EEG bands of interest, including the alpha band.ConclusionsA novel real-time ICA method was proposed for improving the EEG quality signal recorded during fMRI acquisition. The results show substantial reduction of different types of artifacts using real-time ICA method.



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A review on brain structures segmentation in magnetic resonance imaging

Publication date: Available online 30 September 2016
Source:Artificial Intelligence in Medicine
Author(s): Sandra González-Villà, Arnau Oliver, Sergi Valverde, Liping Wang, Reyer Zwiggelaar, Xavier Lladó
Background and objectivesAutomatic brain structures segmentation in magnetic resonance images has been widely investigated in recent years with the goal of helping diagnosis and patient follow-up in different brain diseases. Here, we present a review of the state-of-the-art of automatic methods available in the literature ranging from structure specific segmentation methods to whole brain parcellation approaches.MethodsWe divide first the algorithms according to their target structures and then we propose a general classification based on their segmentation strategy, which includes atlas-based, learning-based, deformable, region-based and hybrid methods. We further discuss each category's strengths and weaknesses and analyze its performance in segmenting different brain structures providing a qualitative and quantitative comparison.ResultsWe compare the results of the analyzed works for the following brain structures: hippocampus, thalamus, caudate nucleus, putamen, pallidum, amygdala, accumbens, lateral ventricles, and brainstem. The structures on which more works have focused on are the hippocampus and the caudate nucleus. In general, the accumbens (0.69 mean DSC) is the most difficult structure to segment whereas the structures that seem to get the best results are the brainstem, closely followed by the thalamus and the putamen with 0.88, 0.87 and 0.86 mean DSC, respectively. Atlas-based approaches achieve good results when segmenting the hippocampus (DSC between 0.75 - 0.90), thalamus (0.88 - 0.92) and lateral ventricles (0.83 - 0.93), while deformable methods perform good for caudate nucleus (0.84 - 0.91) and putamen segmentation (0.86 - 0.89).ConclusionsThere is not yet a single automatic segmentation approach that can emerge as a standard for the clinical practice, providing accurate brain structures segmentation. Future trends need to focus on combining multi-atlas methods with learning-based or deformable approaches. Employing atlases to provide spatial robustness and modeling the structures appearance with supervised classifiers or Active Appearance Models could lead to improved segmentation results.



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Head and neck cancer burden and preventive measures in Central and South America

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Sandra Perdomo, Guillermo Martin Roa, Paul Brennan, David Forman, Mónica S. Sierra
Rationale and objectiveCentral and South America comprise one of the areas characterized by high incidence rates for head and neck cancer. We describe the geographical and temporal trends in incidence and mortality of head and neck cancers in the Central and South American region in order to identify opportunities for intervention on the major identified risk factors: tobacco control, alcohol use and viral infections.MethodsWe obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. Age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years were estimated.ResultsBrazil had the highest incidence rates for oral and pharyngeal cancer in the region for both sexes, followed by Cuba, Uruguay and Argentina. Cuba had the highest incidence and mortality rates of laryngeal cancer in the region for males and females. Overall, males had rates about four times higher than those in females. Most countries in the region have implemented WHO recommendations for both tobacco and alcohol public policy control.ConclusionHead and neck squamous-cell cancer (HNSCC) incidence and mortality rates in the Central and South America region vary considerably across countries, with Brazil, Cuba, French Guyana, Uruguay and Argentina experiencing the highest rates in the region. Males carry most of the HNSCC burden. Improvement and implementation of comprehensive tobacco and alcohol control policies as well as the monitoring of these factors are fundamental to prevention of head and neck cancers in the region.



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Foreword

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Christopher Wild, Dr. Lucía Delgado




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Lifestyle factors and prostate-specific antigen (PSA) testing in UK Biobank: Implications for epidemiological research

Publication date: December 2016
Source:Cancer Epidemiology, Volume 45
Author(s): Thomas J. Littlejohns, Ruth C. Travis, Tim J. Key, Naomi E. Allen
BackgroundThe central role of prostate-specific antigen (PSA) testing in the diagnosis of prostate cancer leads to the possibility that observational studies that report associations between risk factors and prostate cancer could be affected by detection bias. This study aims to investigate whether reported risk factors for prostate cancer are associated with PSA testing in a large middle-aged population-based cohort in the UK.MethodsThe cross-sectional association between a wide range of sociodemographic, lifestyle, dietary and health characteristics with PSA testing was examined in 212,039 men aged 40–69 years in UK Biobank.ResultsA total of 62,022 (29%) men reported they had ever had a PSA test. A wide range of factors was associated with a higher likelihood of PSA testing including age, height, education level, family history of prostate cancer, black ethnic origin, not being in paid/self-employment, living with a wife or partner, having had a vasectomy, being diagnosed with cancer or hypertension and having a high dietary intake of cereal, cooked and salad/raw vegetables, fresh fruit and tea. Conversely, socioeconomic deprivation, Asian ethnic origin, current smoking, low alcohol intake, high body-mass index, high coffee consumption and being diagnosed with diabetes, heart disease or stroke were associated with a lower likelihood of PSA testing.ConclusionsA variety of sociodemographic, lifestyle and health-related characteristics are associated with PSA testing, suggesting that observed associations of some of these traits with risk for prostate cancer in epidemiological studies may be, at least partially, due to detection bias.



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Title page / Editorial Board

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1





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Cancer in Central and South America: Methodology

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Mónica S. Sierra, David Forman
Statistics on cancer incidence from Central and South American countries are scarce because of the small number of population-based cancer registries that continuously collect data. Similarly, comparable statistics on cancer mortality are sparse in spite of efforts made to improve coverage in the last decade. The aim of this study is to describe geographical patterns and trends in cancer incidence and mortality in Central and South America in the 21st century. The primary objective was to obtain the best quality cancer data available from each country within the region. Cancer incidence data were obtained from population-based cancer registries within the region and, in countries where these did not exist, from hospital-based registries; national mortality data were obtained from the World Health Organization mortality database.Given the variability in data quality – mainly due to the age and development in maturity of the registries, an exhaustive review of the data was necessary in order to appropriately analyze, describe and interpret patterns of cancer incidence and mortality between countries and within cancer-specific sites. This paper presents the methods employed in the collection, quality control and analysis of the datasets received for the project.



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Stomach cancer burden in Central and South America

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Monica S. Sierra, Patricia Cueva, Luis Eduardo Bravo, David Forman
Rationale and objectiveStomach cancer mortality rates in Central and South America (CSA) are among the highest in the world. We describe the current burden of stomach cancer in CSA.MethodsWe obtained regional and national-level cancer incidence data from 48 population-based registries (13 countries) and nation-wide cancer deaths from WHO's mortality database (18 countries). We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 and estimated annual percent change to describe time trends.ResultsStomach cancer was among the 5 most frequently diagnosed cancers and a leading cause of cancer mortality. Between CSA countries, incidence varied by 6-fold and mortality by 5–6-fold. Males had up to 3-times higher rates than females. From 2003 to 2007, the highest ASRs were in Chile, Costa Rica, Colombia, Ecuador, Brazil and Peru (males: 19.2–29.1, females: 9.7–15.1). The highest ASMRs were in Chilean, Costa Rican, Colombian and Guatemalan males (17.4–24.6) and in Guatemalan, Ecuadorian and Peruvian females (10.5–17.1). From 1997 to 2008, incidence declined by 4% per year in Brazil, Chile and Costa Rica; mortality declined by 3–4% in Costa Rica and Chile. 60–96% of all the cancer cases were unspecified in relation to gastric sub-site but, among those specified, non-cardia cancers occurred 2–13-times more frequently than cardia cancers.ConclusionThe variation in rates may reflect differences in the prevalence of Helicobacter pylori infection and other risk factors. High mortality may additionally reflect deficiencies in healthcare access. The high proportion of unspecified cases calls for improving cancer registration processes.



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Supplement title page

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1





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Table of contents

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1





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Cancer in Central and South America: Introduction

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): David Forman, Monica S. Sierra
Central and South American countries (including Cuba) are experiencing rapid socio-demographic and epidemiologic changes and the nature of health problems are undergoing transition from infectious to chronic diseases, including cancer. Countries are poorly prepared to respond effectively to the subsequent challenges posed by the new patterns of disease. Existing data delineating the number of cancer cases and the distribution of cancer types from each country in the region are sparse due to limitations on health information systems for recording incidence and mortality despite improvements made in recent years. There is an urgent need for reliable statistics on cancer to inform governmental entities responsible for cancer control in the region. We attempted to obtain the best available cancer data from each country located in the region to provide an overview of current geographic patterns of cancer incidence and mortality in the 21st century.



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Cancer patterns and trends in Central and South America

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Mónica S. Sierra, Isabelle Soerjomataram, Sébastien Antoni, Mathieu Laversanne, Marion Piñeros, Esther de Vries, David Forman
Rationale and objectiveCancer burden is increasing in Central and South America (CSA). We describe the current burden of cancer in CSA.MethodsWe obtained regional and national-level cancer incidence data from 48 population-based registries (13 countries) and nation-wide cancer mortality data from the WHO (18 countries). We estimated world population age-standardized incidence and mortality rates per 100,000 person-years.ResultsThe leading cancers diagnosed were prostate, lung, breast, cervix, colorectal, and stomach, which were also the primary causes of cancer mortality. Countries of high/very high human development index (HDI) in the region experienced a high burden of prostate and breast cancer while medium HDI countries had a high burden of stomach and cervical cancers. Between countries, incidence and mortality from all cancers combined varied by 2–3-fold. French Guyana, Brazil, Uruguay, and Argentina had the highest incidence of all cancers while Uruguay, Cuba, Argentina, and Chile had the highest mortality. Incidence of colorectum, prostate and thyroid cancers increased in Argentina, Brazil, Chile and Costa Rica from 1997 to 2008, while lung, stomach and cervical cancers decreased.ConclusionCSA carries a double-burden of cancer, with elevated rates of infection- and lifestyle-related cancers. Encountered variation in cancer rates between countries may reflect differences in registration practices, healthcare access, and public awareness. Resource-dependent interventions to prevent, early diagnose, and treat cancer remain an urgent priority. There is an overwhelming need to improve the quality and coverage of cancer registration to guide and evaluate future cancer control policies and programs.



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The burden of oesophageal cancer in Central and South America

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Enrique Barrios, Monica S. Sierra, Carina Musetti, David Forman
Rationale and objectiveOesophageal cancer shows marked geographic variations and is one of the leading causes of cancer death worldwide. We described the burden of this malignancy in Central and South America.MethodsRegional and national level incidence data were obtained from 48 population-based cancer registries in 13 countries. Mortality data were obtained from the WHO mortality database. Incidence of oesophageal cancer by histological subtype were available from high-quality population-based cancer registries.ResultsMales had higher incidence and mortality rates than females (male-to-female ratios: 2–6:1 and 2–5:1). In 2003–2007, the highest rates were in Brazil, Uruguay, Argentina and Chile. Mortality rates followed the incidence patterns. Incidence of oesophageal squamous cell carcinoma (SCC) was higher than adenocarcinoma (AC), except in females from Cuenca (Ecuador). SCC and AC incidence were higher in males than females, except in the Region of Antofagasta and Valdivia (Chile), Manizales (Colombia) and Cuenca (Ecuador). Incidence and mortality rates tended to decline in Argentina, Chile, Brazil (incidence) and Costa Rica from 1997 to 2008.ConclusionThe geographic variation and sex disparity in oesophageal cancer across Central and South America may reflect differences in the prevalence of tobacco smoking and alcohol consumption which highlights the need to implement and/or strengthen tobacco and alcohol control policies. Maté consumption, obesity, diet and Helicobacter pylori infection may also explain the variation in oesophageal cancer rates but these relationships should be evaluated. Continuous monitoring of oesophageal cancer rates is necessary to provide the basis for cancer prevention and control in the region.



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Burden of colorectal cancer in Central and South America

Publication date: September 2016
Source:Cancer Epidemiology, Volume 44, Supplement 1
Author(s): Monica S. Sierra, David Forman
Rationale and objectiveThe colorectal cancer (CRC) burden is increasing in Central and South American due to an ongoing transition towards higher levels of human development. We describe the burden of CRC in the region and review the current status of disease control.MethodsWe obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, as well as cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years for 2003–2007 and the estimated annual percentage change for 1997–2008.ResultsThe CRC rate in males was 1–2 times higher than that in females. In 2003–2007, the highest ASRs were seen in Uruguayan, Brazilian and Argentinean males (25.2–34.2) and Uruguayan and Brazilian females (21.5–24.7), while El Salvador had the lowest ASR in both sexes (males: 1.5, females: 1.3). ASMRs were<10 for both sexes, except in Uruguay, Cuba and Argentina (10.0–17.7 and 11.3–12.0). CRC incidence is increasing in Chilean males. Most countries have national screening guidelines. Uruguay and Argentina have implemented national screening programs.ConclusionGeographic variation in CRC and sex gaps may be explained by differences in the prevalence of obesity, physical inactivity, diet, smoking and alcohol consumption, early detection, and cancer registration practices. Establishing optimal CRC screening programs is challenging due to lack of healthcare access and coverage, funding, regional differences and inadequate infrastructure, and may not be feasible. Given the current status of CRC in the region, data generated by population-based cancer registries is crucial for cancer control planning.



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Leptomeningeal metastasis from gynecologic 1 cancers diagnosed by brain MRI

Publication date: Available online 30 September 2016
Source:Clinical Imaging
Author(s): Masafumi Toyoshima, Keita Tsuji, Shogo Shigeta, Hideki Tokunaga, Kiyoshi Ito, Yoh Watanabe, Kosuke Yoshinaga, Takeo Otsuki, Hitoshi Niikura, Nobuo Yaegashi
Leptomeningeal metastasis (LM) is rarely observed in gynecologic cancers. As gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is highly effective for diagnosing LM, the aim of this study is to describe the clinical behaviors and outcomes of LM patients who were diagnosed by Gd-MRI. After securing institutional review board approvals, we retrospectively reviewed patient records. Eight patients were found to have LM from gynecological malignancies. Primary tumors included three ovarian, one tubal, one peritoneal, two endometrial, and one cervical cancer. Gd-MRI of the brain and the spine is indicated as the high priority inspection for the diagnosis of this devastating complication.



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Using Speed of Sound Imaging to Characterize Breast Density

Publication date: Available online 29 September 2016
Source:Ultrasound in Medicine & Biology
Author(s): Mark Sak, Neb Duric, Peter Littrup, Lisa Bey-Knight, Haythem Ali, Patricia Vallieres, Mark E. Sherman, Gretchen L. Gierach
A population of 165 women with negative mammographic screens also received an ultrasound tomography (UST) examination at the Karmanos Cancer Institute in Detroit, MI. Standard statistical techniques were employed to measure the associations between the various mammographic- and UST-related density measures and various participant characteristics such as age, weight and height. The mammographic percent density (MPD) was found to have similar strength associations with UST mean sound speed (Spearman coefficient, rs = 0.722, p < 0.001) and UST median sound speed (rs = 0.737, p < 0.001). Both were stronger than the associations between MPD with two separate measures of UST percent density, a k-means (rs = 0.568, p < 0.001) or a threshold (rs = 0.715, p < 0.001) measure. Segmentation of the UST sound speed images into dense and non-dense volumes showed weak to moderate associations with the mammographically equivalent measures. Relationships were found to be inversely and weakly associated between age and the UST mean sound speed (rs = −0.239, p = 0.002), UST median sound speed (rs = −0.226, p = 0.004) and MPD (rs = −0.204, p = 0.008). Relationships were found to be inversely and moderately associated between body mass index (BMI) and the UST mean sound speed (rs = −0.429, p < 0.001), UST median sound speed (rs = −0.447, p < 0.001) and MPD (rs = −0.489, p < 0.001). The results confirm and strengthen findings presented in previous work indicating that UST sound speed imaging yields viable markers of breast density in a manner consistent with mammography, the current clinical standard. These results lay the groundwork for further studies to assess the role of sound speed imaging in risk prediction.



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Detection and Removal of Ceramic Clip Markers from Breast Tissue by Ultrasound-Guided, Vacuum-Assisted Minimally Invasive Biopsy in a Turkey Breast Model

Publication date: Available online 29 September 2016
Source:Ultrasound in Medicine & Biology
Author(s): Benedikt Schaefgen, Jörg Heil, Hannah Richter, Aba Harcos, Christina Gomez, Anne Stieber, Christof Sohn, Michael Golatta
This article explores the ability of sonographically guided, vacuum-assisted minimally invasive biopsy (VAB) to detect and remove ceramic clip markers from breast tissue. This is a feasibility pre-study for a clinical study using vacuum-assisted biopsy to predict pathologic complete response of breast cancer. Twenty-six ceramic clip markers were placed in five turkey breasts. Clip markers were then detected sonographically and removed using VAB by experienced physicians. Quality of visibility was graded by the performing doctors. The specimens were examined macroscopically to see if they contained the clip marker. The main outcome measure was the accuracy of VAB to detect and remove the clip marker. The VAB device was inspected for any damage possibly caused by hitting the clip marker. The clip markers were detected in 25 cases (96.2%). Twenty clip markers (76.9%) were removed completely by VAB and five (19.2%) were partially removed. One clip marker (3.8%) was not removed. On average, detection of the clip marker took 67 s and the biopsy took 178 s. Quality of visibility was mostly graded as very good (14 cases/53.8%) or good (nine cases/34.6%), and in all of these cases the clip marker was at least partially removed. The clip marker was visible and removed in the vast majority of the cases. VAB is able to remove the clip marker in integrity without causing damage to the system.



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Comparison between Quantitative Stiffness Measurements and Ultrasonographic Findings of Fresh Carotid Plaques

Publication date: Available online 29 September 2016
Source:Ultrasound in Medicine & Biology
Author(s): Kosuke Kondo, Masaaki Nemoto, Naoyuki Harada, Daisuke Fukushima, Hiroyuki Masuda, Nobuo Sugo
Using a stiffness meter, we quantitatively measured the stiffness of fresh plaques that had been excised by carotid endarterectomy. The objective of this study was to clarify the correlation between plaque stiffness and pre-operative carotid ultrasonographic findings, and predict the stiffness of plaques before surgery by comparison with the stiffness of common items. The study population comprised 44 patients (44 lesions) who had undergone carotid endarterectomy at our institution between December 2009 and October 2014. The stiffness of excised fresh plaques was measured using a stiffness meter and compared with the pre-operative echographic findings for the plaques and the stiffness of selected foods and common items. The mean stiffness value for all plaques was 4.52 ± 3.30 MPa (mean ± standard deviation). The plaques exhibiting calcification were significantly harder (p = 0.001). On classification of lesions on the basis of echographic findings, plaque hardness was in the order low-echoic (15 lesions) < iso-echoic (20 lesions) < high-echoic (9 lesions) (p = 0.02). The stiffness of the low-echoic group was equivalent to that of tofu or sliced cheese, whereas the plaques in the iso- and high-echoic groups exhibited stiffness similar to that of ham and a plastic eraser, respectively. A significant correlation was observed between the quantitative stiffness values of carotid plaques and their brightness on carotid ultrasonography. Using these data, operators might be able to predict plaque stiffness from pre-operative echographic findings. In addition, it might be useful for operators to compare such quantitative stiffness measurements with stiffness data for foods and common items to gain an understanding of the state of the target plaque before treatment.



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The CAMSAP3-ACF7 Complex Couples Noncentrosomal Microtubules with Actin Filaments to Coordinate Their Dynamics

Publication date: Available online 29 September 2016
Source:Developmental Cell
Author(s): Wenxiu Ning, Yanan Yu, Honglin Xu, Xiaofei Liu, Daiwei Wang, Jing Wang, Yingchun Wang, Wenxiang Meng
For adaptation to complex cellular functions, dynamic cytoskeletal networks are required. There are two major components of the cytoskeleton, microtubules and actin filaments, which form an intricate network maintaining an exquisite cooperation to build the physical basis for their cellular function. However, little is known about the molecular mechanism underlying their synergism. Here, we show that in Caco2 epithelial cells, noncentrosomal microtubules crosstalk with F-actin through their minus ends and contribute to the regulation of focal adhesion size and cell migration. We demonstrate that ACF7, a member of the spectraplakin family of cytoskeletal crosslinking proteins, interacts with Nezha (also called CAMSAP3) at the minus ends of noncentrosomal microtubules and anchors them to actin filaments. Those noncentrosomal microtubules cooperate with actin filaments through retrograde flow to keep their length and orientation perpendicular to the cell edge as well as regulate focal adhesion size and cell migration.

Graphical abstract

Teaser

Coordination of the microtubule and actin cytoskeletons is required for their cellular function. Ning, Yu, et al. uncover crosstalk between noncentrosomal microtubules and F-actin in epithelial cells. Cytoskeleton crosslinking protein ACF7 and noncentrosomal microtubule minus-end-tracking protein CAMSAP3 anchor microtubules to actin filaments to regulate focal adhesion size and cell migration.


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Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons

Publication date: Available online 29 September 2016
Source:Developmental Cell
Author(s): Saori R. Yoshii, Akiko Kuma, Takumi Akashi, Taichi Hara, Atsushi Yamamoto, Yoshitaka Kurikawa, Eisuke Itakura, Satoshi Tsukamoto, Hiroshi Shitara, Yoshinobu Eishi, Noboru Mizushima
Autophagy is a cytoplasmic degradation system that is important for starvation adaptation and cellular quality control. Previously, we reported that Atg5-null mice are neonatal lethal; however, the exact cause of their death remains unknown. Here, we show that restoration of ATG5 in the brain is sufficient to rescue Atg5-null mice from neonatal lethality. This suggests that neuronal dysfunction, including suckling failure, is the primary cause of the death of Atg5-null neonates, which would further be accelerated by nutrient insufficiency due to a systemic failure in autophagy. The rescued Atg5-null mouse model, as a resource, allows us to investigate the physiological roles of autophagy in the whole body after the neonatal period. These rescued mice demonstrate previously unappreciated abnormalities such as hypogonadism and iron-deficiency anemia. These observations provide new insights into the physiological roles of the autophagy factor ATG5.

Graphical abstract

Teaser

Loss of the key autophagy factor Atg5 causes neonatal lethality. Yoshii, Kuma et al. show that neuron-specific transgenic expression of ATG5 can rescue lethality, suggesting that neuronal dysfunction is the primary cause of lethality. Rescued mice develop multiple abnormalities and provide a resource for dissection of physiological roles of autophagy.


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Cell-Intrinsic Adaptation Arising from Chronic Ablation of a Key Rho GTPase Regulator

Publication date: Available online 29 September 2016
Source:Developmental Cell
Author(s): Berati Cerikan, Ranad Shaheen, Georgina P. Colo, Christine Gläßer, Shoji Hata, Klaus-Peter Knobeloch, Fowzan S. Alkuraya, Reinhard Fässler, Elmar Schiebel
Genome-editing technologies allow systematic inactivation of human genes. Whether knockout phenotypes always reflect gene functions as determined by acute RNAi is an important question. Here we show how the acute knockdown of the Adams-Oliver syndrome (AOS) gene DOCK6, coding for a RAC1/CDC42 guanine nucleotide exchange factor, results in strikingly different phenotypes to those generated by genomic DOCK6 disruption. Cell-intrinsic adaptation compensates for loss of DOCK6 function. Prolonged DOCK6 loss impacts upon the MRTF-A/SRF transcription factor, reducing levels of the ubiquitin-like modifier ISG15. Reduced ISGylation of the IQGAP1 protein increases levels of active CDC42 and RAC1 to compensate for DOCK6 disruption. Similar downregulation of ISG15 in cells from DOCK6 AOS patients indicates that such adaptation can compensate for genetic defects during development. Thus, phenotypes of gene inactivation are critically dependent on the timescale, as acute knockdown reflects a transient state of adjustment to a new equilibrium that is attained following compensation.

Teaser

Cerikan et al. describe the mechanism behind a cell-intrinsic adaptation to DOCK6 gene function loss. They show that DOCK6-GEF loss induces increased monomeric actin levels, negatively regulating the levels of ISG15 through MRTF-A/SRF transcription machinery. Decreased ISG15 levels reduce the ISGylation of IQGAP1, resulting in restoration of the active CDC42/RAC1 levels.


http://ift.tt/2d1vBfU

TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct Autophagy in Endomembrane Damage Homeostasis

Publication date: Available online 29 September 2016
Source:Developmental Cell
Author(s): Santosh Chauhan, Suresh Kumar, Ashish Jain, Marisa Ponpuak, Michal H. Mudd, Tomonori Kimura, Seong Won Choi, Ryan Peters, Michael Mandell, Jack-Ansgar Bruun, Terje Johansen, Vojo Deretic
Selective autophagy performs an array of tasks to maintain intracellular homeostasis, sterility, and organellar and cellular functionality. The fidelity of these processes depends on precise target recognition and limited activation of the autophagy apparatus in a localized fashion. Here we describe cooperation in such processes between the TRIM family and Galectin family of proteins. TRIMs, which are E3 ubiquitin ligases, displayed propensity to associate with Galectins. One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner. TRIM16, through integration of Galectin- and ubiquitin-based processes, coordinated recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1, ULK1, and Beclin 1 in response to damaged endomembranes. TRIM16 affected mTOR, interacted with TFEB, and influenced TFEB's nuclear translocation. The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion.

Graphical abstract

Teaser

Selective autophagy contributes to intracellular homeostasis. Chauhan, Kumar, Jain, Ponpuak et al. show that TRIM family proteins, via interactions with Galectin proteins, recognize membrane damage and direct autophagic homeostasis of lysosomal and phagosomal organelles. They function by assembling core autophagy factors and influencing mTOR and TFEB activity.


http://ift.tt/2dqv0YY

Metabolic health profile in young adults with Prader-Willi syndrome: Results of a 2-year randomised, placebo-controlled, cross-over GH trial

Abstract

Context

Patients with Prader-Willi syndrome (PWS) have an increased fat mass and decreased lean body mass. GH-treated young adults with PWS who have attained adult height benefit from continuation of growth hormone (GH) treatment, as GH maintained their improved body composition, whereas fat mass increased during the placebo period. Adults with PWS are predisposed to T2DM and CVD. Whether GH affects metabolic health profile of this patient group is unknown.

Objective

To investigate the effects of GH versus placebo on metabolic health, in young adults with PWS who were GH-treated for many years during childhood and had attained adult height (AH).

Method

2-year, randomised, double-blind, placebo-controlled cross-over study with stratification for gender and BMI in 27 young adults with PWS. Intervention with GH (0.67 mg/m²/day) and placebo, both for 1 year duration.

Results

Compared to placebo, GH treatment resulted in similar glucose and insulin levels during oral glucose tolerance test. Only fasting glucose and insulin were slightly higher during GH versus placebo (+0.2 mmol/l and +18.4 pmol/l), although both remained within normal ranges in both phases. Blood pressure and lipid profile were similar after GH versus placebo. At baseline (AH) and during GH, no patients had metabolic syndrome, while 1 developed it during placebo treatment.

Conclusions

GH treatment has no adverse effects on metabolic health profile. Thus, GH-treated young adults with PWS who have attained AH benefit from continuation of GH treatment without safety concerns regarding metabolic health.

This article is protected by copyright. All rights reserved.

http://ift.tt/2cGpQbC

13 Biocompatibility of biodegradable medical polymers

Publication date: 2017
Source:Science and Principles of Biodegradable and Bioresorbable Medical Polymers
Author(s): D. Ozdil, I. Wimpenny, H.M. Aydin, Y. Yang
Biomaterials have various applications in the medical field; whilst biodegradable biomaterials play an important role in regenerative medicine, tissue engineering and drug delivery. In addition to conversional biocompatibility, biodegradable materials have to meet additional requirements to cover the biocompatibility of bulk materials, the degraded by-products duration of their presence in vivo and the dynamic integrity for the target applications. Chemical compatibility is the primary requisite. The bulk materials, as well as their degraded products have to be compatible with the biological environment; whilst the importance of the mechanical compatibility, which refers to matching the dynamic request of scaffolds in tissue regeneration is attracting more attention for new material development. This chapter highlights the principle of biocompatibility of biodegradable materials. Interactions between degradable polymers and biological systems have been discussed, from which the design principles to ensure biocompatibility for medical applications for biomaterials have been emphasized.



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Pri-miR-34b/c rs4938723 polymorphism is associated with the risk of childhood acute lymphoblastic leukemia

Publication date: Available online 30 September 2016
Source:Cancer Genetics
Author(s): Mohammad Hashemi, Gholamreza Bahari, Majid Naderi, Simin Sadeghi-Bojd, Mohsen Taheri
MicroRNAs (miRNAs), small noncoding regulatory RNAs, are key regulators of gene expression. The impact of Pri-miR-34b/c rs4938723 variant on development of various cancer is still controversial. In the present study, we examined whether a rs4938723 variant located at promoter region of Pri-miR-34b/c is associated with childhood ALL. A total of 110 children with acute lymphoblastic leukemia (ALL) and 120 healthy children were recruited to participate in this study. The rs4938723 variant was genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The rs4938723 variant decrease the risk of ALL in heterozygous (TC vs OR=0.48, 95%CI=0.28-0.84, p=0.012, TC vs TT), and overdominant (OR=0.51, 95%CI=0.30-0.89, p=0.0.020, TC vs TT+CC): OR=1.32, 95%CI=0.67-2.59, p=0.498; C vs T: OR = 0.99, 95%CI = 0.75- 1.31, p=0.986) inheritance models tested. The C allele significantly decreased the risk of childhood ALL compared to T allele (OR=0.52, 95%CI=0.33-0.83, p=0.006). Our findings proposed an association between Pri-miR-34 b/c rs4938723 variant and risk of childhood ALL development in a sample of Iranian population.



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NF-Y and SP transcription factors – new insights in a long-standing liaison

Publication date: Available online 30 September 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Guntram Suske
For long it has been recognized that CCAAT boxes and GC-rich elements co-occur in many human and murine promoters within 100bp upstream of the transcription start site. The trimeric transcription factor NF-Y is the major CCAAT box-binding factor, and members of the SP family of transcription factors are the major GC box-binding proteins. Recent chromatin immunoprecipitations coupled with high throughput sequencing (ChIP-seq) have examined binding of NF-Y and the ubiquitous SP factors SP1, SP2 and SP3 genome-wide, allowing for comprehensive comparison of NF-Y and SP factor actions in the context of chromatin. Here, I attempt a synthesis of the earlier single-promoter type of analysis with the more recent genome-wide studies. In particular, I also discuss different modes of genomic interactions between SP factors and NF-Y that have emerged recently, and identify a key technical issue, which needs to be taken into account in a critical evaluation of genome-wide studies. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease

Graphical abstract

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Interest of Fluorescence in Salvage Surgery for Recurrence of Head and Neck Cancer in Irradiated Area

Condition:   Head and Neck Cancer
Intervention:   Drug: indocyanine green
Sponsor:   Institut de Cancérologie de Lorraine
Not yet recruiting - verified September 2016

http://ift.tt/2d1m6gT

Platelet-rich Plasma Versus Corticosteroid Injection for the Treatment of Femoroacetabular Impingement

Condition:   Femoroacetabular Impingement
Interventions:   Drug: platelet-rich plasma injection;   Drug: corticosteroid injection
Sponsor:   University of Michigan
Recruiting - verified September 2016

http://ift.tt/2dqkBfQ

Safety Study of MGA271 in Refractory Cancer

Conditions:   Prostate Cancer;   Melanoma;   Renal Cell Carcinoma;   Triple-negative Breast Cancer;   Head and Neck Cancer;   Bladder Cancer;   Non-small Cell Lung Cancer
Intervention:   Biological: MGA271
Sponsor:   MacroGenics
Recruiting - verified September 2016

http://ift.tt/2d1lbgx

Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and meta-analysis

Summary

Topical and systemic prophylactic measures, which are administered before the development of epidermal growth factor receptor (EGFR)-related acneiform rash, are appropriate interventions to mitigate the intensity of skin toxicity. We have performed a systematic review and meta-analysis to evaluate whether prophylactic antibiotics may reduce the occurrence and severity of anti-EGFR drug-related skin rashes. A systematic review was performed by searching Medline, Scopus, Embase, CINAHL, LILACS, Web of Science and the Cochrane Library from inception until March 2016 for publications regarding the pre-emptive role of antibiotics for EGFR-induced skin rashes. Fixed- or random-effects meta-analyses, according to heterogeneity, were used to summarize odds ratios of skin toxicity with antibiotic use. Of the 827 citations found in the search, 13 studies comprising 1073 patients were included in the analysis. In 12 studies, patients in the prophylactic antibiotic arms had a lower risk of developing a skin rash (odds ratio 0·53, 95% confidence interval 0·39–0·72, P < 0·01) than patients without antibiotic prophylaxis. In particular, moderate-to-severe toxicities (grades 2–4) were reduced by nearly two-thirds (odds ratio 0·36, 95% confidence interval 0·22–0·60, P < 0·01) in 13 studies. This translated to a 26% absolute difference of high-grade skin rash compared with the control arms (from 50% to 24%). The results of this meta-analysis show that the risk of skin rash after treatment with anti-EGFR agents for solid tumours was significantly lower in patients taking prophylaxis with antibiotics than in those who were not. Therefore, taking pre-emptive tetracyclines for several weeks at the start of anti-EGFR treatment can significantly reduce the incidence and severity of cutaneous acneiform rash.

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Chronic, intractable nodules after filler injection successfully treated with a bipolar radiofrequency device

http://ift.tt/2dAXeRQ

Superficial malignant peripheral nerve sheath tumor with overlying intradermal melanocytic nevus mimicking spindle cell melanoma

ABSTRACT

Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas with histological and immunohistochemical similarities to spindle cell melanoma. Although spindle cell melanoma is significantly more common, both tumors may express S100 and lack staining for HMB-45, Melan-A, or MITF. Here we present a case of superficial malignant peripheral nerve sheath tumor with diffuse S100 positivity arising in a subtle neurofibroma in close proximity to an intradermal melanocytic nevus. This configuration had led to prior misdiagnosis as a desmoplastic melanoma arising in the nevus and to sentinel lymph node biopsy. Identification of the background neurofibroma, as well as CD34 positivity raised consideration of a low grade malignant peripheral nerve sheath tumor, which was confirmed via observation of Schwannian differentiation on electron microscopy. The importance of distinguishing these two tumors is stressed owing to the difference in management.

http://ift.tt/2dfhpmu

Chemotherapy Reaction Induced by Ixabepilone, a Microtubule Stabilizing Agent, Mimicking Extramammary Paget's Disease in a Patient with Breast Carcinoma

Abstract

The histopathologic characteristics of reactions caused by the many novel anticancer agents are under-recognized. We report a case of a 67-year-old female with locally advanced metastatic breast cancer, who initially presented with an extensive reticulated erythematous patch on the trunk caused by intravascular metastases confirmed by a skin biopsy. Due to disease progression, she was started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another skin biopsy was obtained and initially interpreted as extramammary Paget's disease. However, the biopsy showed metaphase arrest of numerous keratinocytes in the basilar and suprabasilar epidermis. Atypical epithelial cells were only present in the intravascular spaces similar to the initial biopsy. Given the temporal association between the initiation of ixabepilone therapy and the epidermal mitotic arrest, a diagnosis of chemotherapy reaction to ixabepilone was rendered. Ixabepilone is an analog of epothilone, a microtubule stabilizer causing mitotic arrest of the cell cycle approved for the treatment of metastatic and locally advanced treatment-resistant breast cancer. The demonstration of epidermal mitotic arrest caused by ixabepilone is without precedent. The case emphasizes the importance of considering a chemotherapy reaction in the histologic differential diagnosis of epidermal mitotic arrest in a cancer patient receiving chemotherapy.

http://ift.tt/2dF2tMW

Concomitant and discrete expressions of aldose reductase and sorbitol dehydrogenase in the male reproductive tract

Publication date: Available online 29 September 2016
Source:Acta Histochemica
Author(s): Muktanand Tripathi, Akhand Pratap Singh, Gopal Gupta, Singh Rajender
This study aimed at investigating the expression and localization of the polyol pathway enzymes; aldose reductase (AR) and sorbitol dehydrogenase (SDH), in the male reproductive tract of rat. Gene expression analysis showed maximum expression of AR and SDH in the coagulating glands. Western blot analysis showed a coordinated presence of the two enzymes in the coagulating glands, seminal vesicle and epididymis. Immunohistochemistry showed a concordant expression of the two enzymes in the coagulating gland, which goes well with its function of fructose production in rats. A less concordant expression of the two enzymes in the seminal vesicle was also seen. Discrete expression of AR was seen in the Sertoli cells without SDH. Germ cells including sperm in the seminiferous tubules lacked AR, but SDH was present in all stages of developing germ cells including sperm present in the seminiferous tubules. The epithelial layer of epididymis showed the presence of AR, but it was negligible in vas deferens and prostate. SDH was not seen in the epithelial layer of epididymis, vas deferens or prostate. Though sperm in the seminiferous tubules lacked AR, sperm extracted from cauda showed the presence of both AR and SDH. Immunofluorescence localization of AR and SDH on sperm showed the presence of both the enzymes all over sperm. Discrete expression of AR in the Sertoli cells may be linked to detoxification of a number of metabolism by-products. Similarly, the presence of polyol enzymes on sperm in epididymis and beyond may be to tackle toxic metabolites they may encounter during their journey along the male or female reproductive tract.



http://ift.tt/2dEUY8x

Effect of core ceramic grinding on fracture behaviour of bilayered zirconia veneering ceramic systems under two loading schemes

Publication date: Available online 29 September 2016
Source:Dental Materials
Author(s): Yu-tao Jian, Tian-yu Tang, Michael V. Swain, Xiao-dong Wang, Ke Zhao
ObjectiveThe aim of this in vitro study was to evaluate the effect of core ceramic grinding on the fracture behaviour of bilayered zirconia under two loading schemes.MethodsInterfacial surfaces of sandblasted zirconia disks (A) were ground with 80 (B), 120 (C) and 220 (D) grit diamond discs, respectively. Surface roughness and topographic analysis were performed using a confocal scanning laser microscope (CSLM) and a scanning electron microscopy (SEM). Relative monoclinic content was evaluated using X-ray diffraction analysis (XRD) then reevaluated after simulated veneer firing. Biaxial fracture strength (σ) and Weibull modulus (m) were calculated either with core in compression (subgroup Ac-Dc) or in tension (subgroup At-Dt). Facture surfaces were examined by SEM and energy dispersive X-ray spectroscopy (EDS). Maximum tensile stress at fracture was estimated by finite element analysis. Statistical data analysis was performed using Kruskal–Wallis and one-way ANOVA at a significance level of 0.05.ResultsAs grit size of the diamond disc increased, zirconia surface roughness decreased (p<0.001). Thermal veneering treatment reversed the transformation of monoclinic phase observed after initial grinding. No difference in initial (p=0.519 for subgroups Ac-Dc) and final fracture strength (p=0.699 for subgroups Ac-Dc; p=0.328 for subgroups At-Dt) was found among the four groups for both loading schemes. While coarse grinding slightly increased final fracture strength reliability (m) for subgroups Ac-Dc. Two different modes of fracture were observed according to which material was on the bottom surface. Components of the liner porcelain remained on the zirconia surface after fracture for all groups.SignificanceTechnician grinding changed surface topography of zirconia ceramic material, but was not detrimental to the bilayered system strength after veneer application. Coarse grinding slightly improved the fracture strength reliability of the bilayered system tested with core in compression. It is recommended that veneering porcelain be applied directly after routine lab grinding of zirconia ceramic, and its application on rough zirconia cores may be preferred to enhance bond strength.



http://ift.tt/2cG0RoT

Is the hypothalamic–pituitary–adrenal axis disrupted in type 2 diabetes mellitus?

http://ift.tt/2dpRc59

Folliculitis in prurigo pigmentosa: a proposed pathogenesis based on clinical and pathological observation

ABSTRACT

Background

Prurigo pigmentosa is a rare inflammatory dermatosis whose exact etiology is not understood yet. The purpose of this study was to provide evidence of hair follicle involvement in the pathogenesis by analyzing its clinicopathologic features.

Methods

Patients who fulfilled both the clinical and histological diagnostic criteria of prurigo pigmentosa were recruited. Their histopathologic findings, clinical features, and medical histories were analyzed.

Results

Thirty-two confirmed patients were enrolled from 2002 to 2013. Their ages ranged from 11–79 years with a female predominance. Patient lesions were primarily reddish-brown and located on the back. Twenty-five patients (78%) had pathological involvement of hair follicles, either bacterial colonies in the hair follicles (21/32, 66%), folliculitis (8/32, 25%), or perifolliculitis (15/32, 47%). There was a significantly higher proportion of patients with hair follicle involvement compared to control groups with either non-inflammatory (5/43, 12%, p < 0.001) or inflammatory skin diseases (12/32, 38%, p = 0.002) on the back. Minocycline was an effective antibiotic treatment either singly or in combination with steroids.

Conclusions

The frequent presence of bacterial colonies along with sequelae of inflammatory changes on biopsy provides new evidence to support the theory that prurigo pigmentosa is a reactive inflammation associated with bacterial folliculitis.

http://ift.tt/2dgnugW

MYC amplification in angiosarcomas arising in the setting of chronic lymphedema of morbid obesity

Abstract

Background

Angiosarcoma is a malignancy of vascular endothelial cells which may arise secondarily as a complication of lymphedema, including chronic lymphedema of morbid obesity. Amplifications in MYC are frequently present in secondary angiosarcoma (arising in irradiated sites and chronic lymphedema) and less frequently in primary cutaneous angiosarcoma.

Objective

To describe the presence of MYC amplifications in two cases of cutaneous angiosarcoma secondary to chronic lymphedema of morbid obesity.

Methods

This study is a case series of two patients with cutaneous angiosarcoma. Clinical data was retrieved from the medical records. Histopathological analysis of the biopsy specimens was performed, including immunohistochemistry, along with fluorescence in situ hybridization.

Results

Angiosarcoma arose in the setting of massive chronic lymphedema complicating morbid obesity without other predisposing risk factors. Both cases exhibited epithelioid cell morphology and high-level MYC amplification.

Conclusion

We report MYC amplification in two cases of angiosarcoma arising in massive chronic lymphedema of morbid obesity.

http://ift.tt/2dJToVP

THE UTILIZATION OF SPITZ-RELATED NOMENCLATURE IN THE HISTOLOGICAL INTERPRETATION OF CUTANEOUS MELANOCYTIC LESIONS BY PRACTICING PATHOLOGISTS

ABSTRACT

Background

Spitz nevi, atypical Spitz tumors and spitzoid melanomas ("spitzoid lesions") represent controversial and poorly understood cutaneous melanocytic lesions that are difficult to diagnose histologically. It is unknown how these terms are used by pathologists.

Methods

We describe use of Spitz-related terminology using data from the Melanoma Pathology (M-Path) study database comprising pathologists' interpretations of biopsy slides, a nation-wide study evaluating practicing U.S. pathologists' (N = 187) diagnoses of melanocytic lesions (8,976 independent diagnostic assessments on 240 total test cases, with one slide per case).

Results

Most pathologists (90%) used the Spitz-related terminology. However, significant variation exists in which specific lesions were diagnosed as spitzoid and in the corresponding treatment recommendations. Recommendations ranged from 'no further treatment' to 'wide excision of 10 mm or greater' with no category capturing more than 50% of responses. For spitzoid melanoma diagnoses, 90% of pathologists recommended excision with ≥10 mm margin. Pathologists report less confidence in diagnosing these lesions compared with other melanocytic proliferations and are more likely to request second opinions and additional clinical information (all p < 0.05).

Conclusions

Spitzoid lesions are often not classified in any standardized way, evoke uncertainty in diagnosis by pathologists, and elicit variability in treatment recommendations.

http://ift.tt/2dgoTUE

Cutaneous Nodular Fasciitis with Genetic Analysis: A Case Series

Abstract

Nodular fasciitis is a benign self-limited myofibroblastic neoplasm, which usually involves the upper extremities and trunk of young patients. These tumors have been shown to harbor a translocation involving the MYH9 and USP6 genes, leading to overexpression of the latter. We report seven cases of nodular fasciitis with cutaneous presentations. All cases involved the dermis, with six involving the superficial subcutis, and one auricular tumor extending into cartilage. All cases showed USP6 rearrangement by fluorescence in situ hybridization; in two of three cases, the characteristic MYH9-USP6 fusion was demonstrated by RT-PCR. All patients underwent conservative resection. Nodular fasciitis is an uncommon mesenchymal neoplasm that can occasionally present in superficial locations and is sometimes mistaken for a malignant process. Molecular testing can be useful to distinguish this entity from other cutaneous spindle cell tumors.

http://ift.tt/2dAGb2a

Scholar : Aphasiology, Volume 30, Issue 12, December 2016 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Aphasiology, Volume 30, Issue 12, December 2016 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles The language of the cerebellum Kim van Dun, Mario Manto & Peter Mariën Pages: 1378-1398 | DOI: 10.1080/02687038.2015.1132297 Theory of mind impairment after right-hemisphere damage Noga Balaban, Naama Friedmann & Margalit Ziv Pages: 1399-1423 | DOI: 10.1080/02687038.2015.1137275 The effect of theory of mind impairment on language: Referring after right-hemisphere damage Noga Balaban, Naama Friedmann & Mira Ariel Pages: 1424-1460 | DOI: 10.1080/02687038.2015.1137274 Incorporating principles of the collaborative contextualised intervention approach with the empirical study of learning and communication in traumatic brain injury Rupa Gupta Gordon & Melissa C. Duff Pages: 1461-1482 | DOI: 10.1080/02687038.2015.1136050 Auditory-verbal analysis in aphasia Laurence Schneider, Lucas Spierer, Philippe Maeder, Jocelyne Buttet Sovilla & Stephanie Clarke Pages: 1483-1511 | DOI: 10.1080/02687038.2016.1140119 Miscellaneous Editorial Board Pages: ebi-ebi | DOI: 10.1080/02687038.2016.1243298 Routledge Pioneers of Psychoanalysis Free Access Article Collection - Click here: http://ift.tt/2cwV9Xh This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

The effects of konjac oligosaccharide on TNBS-induced colitis in rats

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Ruixue Liu, Yongchao Li, Bo Zhang
The purpose of the study was to assess the effects and the protective mechanism of konjac oligosaccharide (KOS) on the ulcerative colitis (UC) model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. KOS (1.0 and 4.0g/kg/day) was administered for 14days after the induction of colitis with TNBS. The status of the rats was assessed by morphological and biochemical methods. The effect of KOS on the colonic microflora was also assessed by studying the bacteria profile and short chain fatty acids (SCFAs) production in feces by standard culture techniques and gas chromatography, respectively. KOS administration improved rat weight, colonic length, damage score, structure of gut microbiota, production of SCFA, and reduced colon tissue levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Therefore, our results indicate that KOS is an anti-inflammatory and could be useful as a prebiotic to design functional foods for UC.



http://ift.tt/2dEHERy

Anticancer effect of SZC015 on lung cancer cells through ROS-dependent apoptosis and autophagy induction mechanisms in vitro

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Bin Sun, Lei Gao, Anil Ahsan, Peng Chu, Yanlin Song, Hailong Li, Zonghui Zhang, Yuan Lin, Jinyong Peng, Zhicheng Song, Shisheng Wang, Zeyao Tang
Oleanolic acid (OA) and its several derivatives possess various pharmacological activities, such as antitumor and anti-inflammation. In present study, anticancer effect of SZC015, an OA derivative, and its underlying mechanisms were investigated. We demonstrated that cell viability was significantly decreased in SZC015-treated lung cancer cells, but has less cytotoxicity in human bronchial epithelial cell line. Further investigation verified that apoptosis and autophagy induction and G0/G1 phase arrest were observed in SZC015-treated H322 cells. Mechanically, the level of Akt, p-Akt, p-IκBα, and total p65, the p-p65 in the cytoplasm and nucleus were suppressed by SZC015 in H322 cells, respectively. Inhibition of p65 nuclear translocation was also confirmed by immunofluorescence staining. In addition, co-treatment with chloroquine, an autophagy inhibitor, significantly inhibited SZC015-induced autophagy and enhanced SZC015-induced apoptotic cell death. Intracellular ROS was increased in a concentration-dependent manner, which could be prevented by N-Acetyl l-Cysteine, an ROS scavenger. Moreover, the level of Akt and procaspase-3 were increased, while the ratio of LC3 II/I was decreased. Taken together, our study demonstrates that the inhibitory effect of SZC015 against H322 cells is mediated by excessive ROS generation that could suppress Akt/NF-κB signaling pathway, which thereby leads to apoptotic and autophagic cell death.

Graphical abstract

http://ift.tt/2deX6pv

Targeting mast cells: Uncovering prolific therapeutic role in myriad diseases

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Jatinder Singh, Ramanpreet Shah, Dhandeep Singh
The mast cells are integral part of immune system and they have pleiotropic physiological functions in our body. Any type of abnormal stimuli causes the mast cells receptors to spur the otherwise innocuous mast cells to degranulate and release inflammatory mediators like histamine, cytokines, chemokines and prostaglandins. These mediators are involved in various diseases like allergy, asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the receptors involved in degranulation of mast cells and are broadly divided into four categories: G-protein coupled receptors, ligand gated ion channels, immunoreceptors and pattern recognition receptors. Although, activation of pattern recognition receptors do not cause mast cell degranulation, but result in cytokines production. Degranulation itself is a complex process involving cascade of events like membrane fusion events and various proteins like VAMP, Syntaxins, DOCK5, SNAP-23, MARCKS. Furthermore, we described these mast cell receptors antagonists or agonists useful in treatment of myriad diseases. Like, omalizumab anti-IgE antibody is highly effective in asthma, allergic disorders treatment and recently mechanistic insight of IgE uncovered; matrix mettaloprotease inhibitor marimistat is under phase III trial for inflammation, muscular dystrophy diseases; ZPL-389 (H4 receptor antagonist) is in Phase 2a Clinical Trial for atopic dermatitis and psoriasis; JNJ3851868 an oral H4 receptor antagonist is in phase II clinical development for asthma, rheumatoid arthritis. Therefore, research is still in inchoate stage to uncover mast cell biology, mast cell receptors, their therapeutic role in myriad diseases.



http://ift.tt/2deWZKz

LOX-1 and TLR4 affect each other and regulate the generation of ROS in A. fumigatus keratitis

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Xinran Gao, Guiqiu Zhao, Cui Li, Jing Lin, Nan Jiang, Qian Wang, Liting Hu, Qiang Xu, Xudong Peng, Kun He, Guoqiang Zhu
PurposeTo explore the relationship between LOX-1 and TLR4 in Aspergillus fumigatus (A. fumigatus) keratitis. To determine LOX-1 and TLR4 can affect each other and regulate inflammation through regulation of the generation of reactive oxygen species (ROS) in A. fumigatus keratitis.MethodsThe cornea and abdominal cavity extracted neutrophils of susceptible C57BL/6 mice were infected with A. fumigatus. The cornea and neutrophils were pretreated with LOX-1 neutralizing antibody, Polyinosinic acid (Poly(I)) (the inhibitor of LOX-1) or CLI-095 (the inhibitor of TLR4) separately before infection. LOX-1, TLR4 and IL-1β expression were detected in normal and infected cornea by PCR and Western Blot, while ROS was detected in the neutrophils by flow cytometry.ResultsLOX-1, TLR4, IL-1β mRNA and protein levels were up-regulated in C57BL/6 cornea after infection. LOX-1 neutralizing antibody or Poly(I) pretreatment decreased the expression of LOX-1, TLR4 and IL-1β in C57BL/6 cornea after infection and CLI-095 pretreatment decreased the expression of LOX-1, TLR4 and IL-1β in C57BL/6 cornea after infection. ROS generation was increased in C57BL/6 neutrophils after infection, however, ROS generation was decreased in C57BL/6 neutrophils after infection by LOX-1 neutralizing antibody or Poly(I) or CLI-095 pretreatment.ConclusionLOX-1, TLR4 and IL-1β expression and ROS generation are increased after infection. LOX-1 and TLR4 can affect each other and regulate the generation of ROS in A. fumigatus keratitis. Inhibition of LOX-1 and TLR4 can reduce ROS generation.



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