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

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Τετάρτη 30 Μαΐου 2018

Recent trends in electrochemical biosensors of superoxide dismutases

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Murugesan Balamurugan, Paulraj Santharaman, Thangamuthu Madasamy, Seenivasan Rajesh, Niroj Kumar Sethy, Kalpana Bhargava, Srigiridhar Kotamraju, Chandran Karunakaran
Superoxide dismutases (SODs), a family of ubiquitous enzymes, provide essential protection to biological systems against uncontrolled reactions with oxygen- and nitrogen- based radical species. We review first the role of SODs in oxidative stress and the other biological functions such as peroxidase, nitrite oxidase, thiol oxidase activities etc., implicating its role in neurodegenerative, cardiovascular diseases, and ageing. Also, this review focuses on the development of electrochemical label-free immunosensor for SOD1 and the recent advances in biosensing assay methods based on their catalytic and biological functions with various substrates including reactive oxygen species (superoxide anion radical, hydrogen peroxide), nitric oxide metabolites (nitrite, nitrate) and thiols using thiol oxidase activity. Furthermore, we emphasize the progress made in improving the detection performance through incorporation of the SOD into conducting polymers and nanocomposite matrices. In addition, we address the potential opportunities, challenges, advances in electrochemical-sensing platforms and development of portable analyzer for point-of-care applications.



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MNPs@anionic MOFs/ERGO with the size selectivity for the electrochemical determination of H2O2 released from living cells

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Cong Li, Ruijun Wu, Juncheng Zou, Tingting Zhang, Sufang Zhang, Zhiquan Zhang, Xin Hu, Youqi Yan, Xiaomei Ling
Herein, the ternary composites, ultrasmall metal nanoparticles encapsulated in the anionic metal-organic frameworks/electrochemically reduced graphene oxide (MNPs@Y-1, 4-NDC-MOF/ERGO, M = Ag, Cu) are constructed by a cationic exchange strategy and an electrochemical reduction process for the electrochemical determination of H2O2. Both AgNPs@Y-1, 4-NDC-MOF/ERGO and CuNPs@Y-1, 4-NDC-MOF/ERGO display excellent electrocatalytic activity toward H2O2, but the former is superior to the latter. Such a difference in electrocatalytic activity can be explained by the characterization measurements, and the results manifest MNPs@Y-1, 4-NDC-MOF/ERGO (M = Ag, Cu) electrocatalysts have subequal MNPs sizes and electrochemical surface areas, but different electron transfer rate constants. The AgNPs@Y-1, 4-NDC-MOF/ERGO sensor shows a linear detection range from 4 to 11,000 μM with the detection limit of 0.18 μM. Moreover, MNPs@Y-1, 4-NDC-MOF/ERGO (M = Ag, Cu) exhibit excellent anti-interference performance and can be used for the detection of H2O2 released from living cells. The proposed sensor takes full advantage of the catalytic property of MNPs, the size selectivity of Y-1, 4-NDC-MOF, and the fast electron transport effect of ERGO. Thus, the MNPs@Y-1, 4-NDC-MOF/ERGO/GCE (M = Ag, Cu) can be utilized to detect oxidase activities by monitoring H2O2 produced in the presence of substrate and oxidase, and it is expected that composites with the molecular sieving effect and catalytic activity can be widely applied for catalysis, biomedicine, and biosensing fields.



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Component resolved diagnostic study of cow's milk allergy in infants and young children in northern China

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Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Junpu Li, Jiayi Zhang, Cuiya Qiong, Tiantian She, Ying Bian, Shuxiang Lin, Huiqiang Li
BackgroundIncreasing dairy consumption in China has been accompanied by rising incidence of milk allergy. Here we analyzed profiles of specific immunoglobulin E (sIgE) against cow's milk proteins, and assessed their value for milk allergy diagnosis among infants and young children from northern China.MethodsSera collected from 48 patients with milk allergy and 27 negative control subjects was analyzed by enzyme-linked immunosorbent assay to measure sIgE to α-lactalbumin (Bos d 4), β-lactoglobulin (Bos d 5), α-casein (Bos d 9), β-casein (Bos d 11), and κ-casein (Bos d 12).ResultsAmong milk-allergic individuals, most were sensitized to at least one milk protein; about half were sensitized to Bos d 5, Bos d 9, Bos d 11 and Bos d 12, respectively, while few had positive serum sIgE against Bos d 4. Bos d 12 sIgE had the largest area under curve (AUC) (0.878; 95% CI, 0.800–0.957) and thus showed the best diagnostic performance in discriminating between milk-allergic and non-milk allergic patients, with a sensitivity of 92.6% and specificity of 72.9% using a statistically optimal cut-off value (OD450nm, 0.191). The combinations of Bos d 5 + Bos d 12 showed an AUC of 0.926, which was larger than for any individual components.ConclusionsOur results revealed inter-individual variation in the sensitization to different milk allergen component. Bos d 12 sIgE showed best performance in diagnosing milk allergy. Milk allergy diagnostic accuracy was further improved using combinations of milk allergen components by application of ROC curves based on logistic regression.



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Editorial Board

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Publication date: May 2018
Source:Journal of Anxiety Disorders, Volume 56





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Do acute dissociation reactions predict subsequent posttraumatic stress and growth? A prospective experience sampling method study

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Publication date: Available online 30 May 2018
Source:Journal of Anxiety Disorders
Author(s): Talya Greene
While peritraumatic dissociation has been identified as a predictor of posttraumatic stress disorder, it may also have some protective aspect. The study uses experience sampling methods to assess acute dissociation reactions during conflict, and to investigate these reactions as predictors of subsequent posttraumatic stress symptoms (PTSS) and posttraumatic growth (PTG).During the 2014 Israel-Gaza conflict, Israeli civilians (n = 96) exposed to rocket fire gave twice-daily experience sampling method (ESM) reports of dissociation symptoms for 30 days via mobile phone. PTSS and PTG were assessed two months later. A mixed effects random intercepts and slopes model estimated acute dissociation reactions. Individual slope coefficients for acute dissociative reactivity were entered as predictors of subsequent PTSS and PTG in regression analyses investigating linear and curvilinear associations.Exposure to sirens elicited acute dissociation reactions. Dissociative reactivity gradually reduced over the conflict. Higher acute dissociative reactivity during conflict predicted PTSS in a curvilinear manner (inverted U) and PTG in a positive linear manner two months later.The current study provides an important and novel contribution to the field by using ESM methods to assess peritraumatic dissociation, and in demonstrating that peritraumatic dissociation may be both adaptive and maladaptive, which has implications for risk assessment and clinical practice.



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Are anxiety disorders publications continuing on a trajectory of growth? A look at Boschen’s (2008) predictions and beyond

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Publication date: May 2018
Source:Journal of Anxiety Disorders, Volume 56
Author(s): Gordon J.G. Asmundson, Aleiia J.N. Asmundson
The relative health of a field of research can be approximated by assessing peer-reviewed journal publication trends for articles pertinent to that field. The most recent comprehensive assessment of publication trends in the anxiety disorders indicated that the field was on a continuing trajectory of growth (Boschen, 2008). We conducted an updated search of Medline for publications on each of the anxiety disorders from 2006 to 2016. Results indicated that there was continuing growth in anxiety disorders research overall and, particularly, for posttraumatic stress disorder, social anxiety disorder, generalized anxiety disorder, and obsessive compulsive disorder. Publication trends observed in Medline were also reflected in the focus of papers published in the Journal of Anxiety Disorders over the past 3 years; yet, a substantive number of papers in the journal also dealt with multiple anxiety disorders, anxiety-related constructs, transdiagnostic issues, and conditions with significant overlap with the anxiety disorders. Observed publication trends, shifts in the focus of research attention, and probable future research directions are discussed briefly.



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Obsessive-compulsive disorder research: Growing in scope, advances unclear

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Publication date: May 2018
Source:Journal of Anxiety Disorders, Volume 56
Author(s): Dean McKay
There has been impressive growth in scholarly research on obsessive-compulsive disorder (OCD). As a general rule, this can be construed as a sign of health in the subspecialty within anxiety disorder research. One factor that likely contributed to the growth in research on OCD was the observation that obsessional experiences can be placed on a dimension from normal to abnormal (or non-clinical to clinical) (Rachman and de Silva, 1978). While the dramatic growth in OCD research has led to increased sophistication in clinical conceptualization of various presentations of this heterogeneous condition, it has not led to a commensurate increase in the availability of efficacious treatment. This gap, between awareness of the disorder and delivery of evidence-based treatment, serves as a limiting factor in enthusiasm regarding the growth in research productivity on OCD as a sign of health in the subspecialty.



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Research on social anxiety disorder continues to escalate: A commentary on Asmundson and Asmundson’s analysis of publication trends in the anxiety disorders

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Publication date: May 2018
Source:Journal of Anxiety Disorders, Volume 56
Author(s): Richard G. Heimberg, Rachel M. Butler
Asmundson and Asmundson (2018) reported that publication of research on anxiety disorders, including social anxiety disorder (SAD), has seen rapid growth in the period between 2006 and 2016. In fact, the uptick in publication rate of SAD research was unexpectedly high given previous predictions by Boschen (2008), who reviewed publication trends from 1980 to 2005. In this commentary, we consider potential factors involved in the continued increase in publication of research on SAD. We examine the roles that empathy and evolutionary factors may play in our ability to relate to those with SAD and in our motivation to research it. Further, we consider whether the relatively high prevalence of SAD, the visibility of experiences of social anxiety in the general population, and the availability of viable theoretical models of SAD and its treatment have played a significant role in the high publication rate. Other factors affecting research on SAD such as changes in the definition of SAD in various editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), comorbidity which other psychiatric disorders, and the role of pharmaceutical company research are also discussed.



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The increase in interest in GAD: Commentary on Asmundson & Asmundson

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Publication date: May 2018
Source:Journal of Anxiety Disorders, Volume 56
Author(s): Michelle G. Newman, Amy Przeworski
Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders. It is associated with functional impairment and is unlikely to spontaneously remit. As identified by Asmundson and Asmundson (2018), published research studies on GAD have increased in number over the last decade. We propose that this is due to the high prevalence of the diagnosis and symptoms, interest in transdiagnostic processes, such as worry, increased interest in emotion dysregulation as a principle underlying diagnoses, and new methods of treating and disseminating treatment that may be particularly well suited to GAD. Despite the increase in research articles on GAD, GAD still remains one of the least studied anxiety disorders. We propose that this is due to the misconception that GAD does not lead to severe impairment, despite data showing otherwise. Future research should continue to examine the phenomenology, mechanisms, and treatment of GAD in order to better understand this common anxiety disorder.



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Posttraumatic stress disorder as a growth industry: Comment on Asmundson and Asmundson (2018)

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Publication date: May 2018
Source:Journal of Anxiety Disorders, Volume 56
Author(s): Richard J. McNally
Asmundson and Asmundson's (2018) bibliometric study demonstrates that the anxiety disorders remain a major focus of clinical research. Yet striking differences emerged among these syndromes. For example, in contrast to panic disorder, posttraumatic stress disorder has increasingly flourished as a major focus of publications. The purpose of my commentary is to discuss the basis for the remarkable success of traumatology relative to other areas (e.g., panic disorder research).



https://ift.tt/2sn7Qbc

Immunohistochemical Biomarkers in Diagnosis of Hematolymphoid Neoplasms of Endocrine Organs

Abstract

The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fourth edition of WHO classification of tumors of endocrine organs and the fourth edition of WHO classification of tumors of hematopoietic and lymphoid tissues are recently published. The updates in both fields include some new disease descriptions and prognostic markers. Our aim in this review article is to give practical diagnostic information about the most frequently seen hematolymphoid involvements of the pituitary gland, thyroid, and adrenal tissue. We designed the text in the order of organs and the contents according to the disease frequency. The pituitary gland and cellar region are the most frequently involved with Langerhans cell histiocytosis. Although it is very rare, Erdheim–Chester disease has recently been included in the classification and still needs more clear diagnostic definitions. Lymphoproliferative thyroid lesions and presentations create diagnostic problems for the pathologists. IGG4-related disease and its relation with thyroiditis is a new concept. There are many unknowns on pathobiology of the disease spectrum and discussion on defined diagnostic criteria of the IGG4-related thyroid diseases. The overlapping features of thyroiditis and primary thyroid lymphomas also create diagnostic difficulties. The frequently recognized primary hematolymphoid lesions of the endocrine organs may not be difficult to diagnose since they are expected lesions. The secondary involvement of hematolymphoid neoplasia may be more difficult to diagnose for an endocrine pathologist. In this review article, we aim to give brief description of the diseases and practical diagnostic approach by using optimum markers guided by the latest WHO classifications.



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Obturators versus flaps after maxillary oncological ablation: A systematic review and best evidence synthesis

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Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Yubin Cao, Changhao Yu, Wei Liu, Cheng Miao, Bo Han, Jianong Yang, Longjiang Li, Chunjie Li
Maxillary defects can be resolved by prosthetic obturation, autologous tissue reconstruction, or a combination of both. However, there is still controversy in the selection of the optimal approach. Therefore, the aim of this study was to systematically review evidences comparing the performance of obturators and flaps in patients after maxillary oncological ablation. Both electronic and manual searching approaches were conducted to identify eligible evidence. Two reviewers independently assessed the risk of bias. In addition, the same reviewers independently extracted the data. Meta-analyses were performed using Revman 5.3, and best evidence synthesis was performed. Sixteen studies were included and a total of 528 participants were analyzed. All studies were assessed at low quality. Results of this meta-analysis showed weak evidence in the difference between obturators and flaps on the outcome regarding word intelligibility (P = 0.004) and masticatory efficiency (P = 0.002). However, no differences were detected regarding speech intelligibility and nasalance. All studies were compiled into the best evidence synthesis. The sum of 31 evidences was considered. Twelve evidences were evaluated at a moderate level, such as speech, mastication, pain, salivation, taste sensations, and mouth opening. Except the outcomes of word intelligibility, masticatory efficiency, and mouth pain, other moderate evidences showed no difference between obturators and flaps. In conclusion, both obturators and flaps might be effective in patients' rehabilitation functions after maxillary ablation. However, some advantages were observed when using surgical reconstruction over prosthetic rehabilitation. Additional high-quality studies are needed to provide more solid evidence before applying these results into clinical practice.



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Unravelling the molecular signatures in HNSCC: Is the homogenous paradigm becoming obsolete?

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Publication date: Available online 30 May 2018
Source:Oral Oncology
Author(s): Divya Gopinath, Rohit Kunnath Menon




https://ift.tt/2stBKun

Cancer-induced systemic myeloid dysfunction: implications for treatment and a novel nanoparticle approach for its correction

Publication date: Available online 30 May 2018
Source:Seminars in Oncology
Author(s): Rydell Alvarez, Liliana Oliver, Anet Valdes, Circe Mesa
Unlike other regulatory circuits, cancer-induced myeloid dysfunction involves more than an accumulation of impaired dendritic cells (DCs), protumoral macrophages and myeloid derived suppressor cells (MDSCs) in the tumor microenvironment (TME). It is also characterized by "aberrant" myelopoiesis that results in the accumulation and expansion of immature myeloid precursors with a suppressive phenotype in the systemic circulation. The first part of this review briefly describes the evidence for and consequences of this systemic dysfunctional myelopoiesis and the possible reinforcement of this phenomenon by conventional treatments used in patients with cancer, in particular chemotherapy and G-CSF. The second half of this review describes very small size particles (VSSP), a novel immune-modulatory nanoparticle, and the evidence indicating a possible role of this agent in correcting or re-programming the dysfunctional myelopoiesis in different scenarios.



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Τα σημάδια στα νύχια μπορεί να υποδείξουν πρόβλημα υγείας. http://medicalnews.gr/grammes-nyxia-shmainoun/


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480






Targeting myeloid-derived suppressor cells for cancer immunotherapy

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with an immune suppressive phenotype. They represent a critical component of the immune suppressive niche described in cancer, where they support immune escape and tumor progression through direct effects on both the innate and adaptive immune responses, largely by contributing to maintenance of a high oxidative stress environment. The number of MDSCs positively correlates with protumoral activity, and often diminishes the effectiveness of immunotherapies, which is particularly problematic with the emergence of personalized medicine. Approaches targeting MDSCs showed promising results in preclinical studies and are under active investigation in clinical trials in combination with various immune checkpoint inhibitors. In this review, we discuss MDSC targets and therapeutic approaches targeting MDSC that have the aim of enhancing the existing tumor therapies.



https://ift.tt/2Jii1Iw

Whole-genome RNAi screen identifies methylation-related genes influencing lipid metabolism in Caenorhabditis elegans

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Publication date: Available online 30 May 2018
Source:Journal of Genetics and Genomics
Author(s): Xiaotong Zhu, Yangli Liu, Hong Zhang, Pingsheng Liu
Lipid droplets (LDs) are highly conserved multifunctional cellular organelles and aberrant lipid storage in LDs can lead to many metabolic diseases. However, the molecular mechanisms governing lipid dynamic changes remain elusive, and the high-throughput screen of genes influencing LD morphology was limited by lacking specific LD marker proteins in the powerful genetic tool Caenorhabditis elegans. In this study, we established a new method to conduct whole-genome RNAi screen using LD resident protein DHS-3 as a LD marker, and identified 78 genes involved in significant LD morphologic changes. Among them, mthf-1, as well as a series of methylation-related genes, was found dramatically influencing lipid metabolism. SREBP-1 and SCD1 homologs in C. elegans were involved in the lipid metabolic change of mthf-1(RNAi) worms, and the regulation of ATGL-1 also contributed to it by decreasing triacylglycerol (TAG) hydrolysis. Overall, this study not only identified important genes involved in LD dynamics, but also provided a new tool for LD study using C. elegans, with implications for the study of lipid metabolic diseases.



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Press review

Publication date: Available online 30 May 2018
Source:Journal of Visceral Surgery





https://ift.tt/2H9lF2w

Functional Drink Containing the Extracts of Purple Corn Cob and Pandan Leaves, the Novel Cognitive Enhancer, Increases Spatial Memory and Hippocampal Neuron Density Through the Improvement of Extracellular Signal Regulated Protein Kinase Expression, Cholinergic Function, and Oxidative Status in Ovariectomized Rats

Rejuvenation Research, Ahead of Print.


https://ift.tt/2H771sp

An independent relation of atopic dermatitis to exercise-induced wheezing in asthmatic children

Publication date: Available online 30 May 2018
Source:Allergology International
Author(s): Satoshi Honjo, Yoko Murakami, Hiroshi Odajima, Yuichi Adachi, Koichi Yoshida, Yukihiro Ohya, Akira Akasawa
BackgroundAtopic dermatitis (AD) and exercise-induced asthma (EIA) are common in asthmatic children, and exercise is the most common trigger other than infection for acute onset asthma attack in children. We examined whether AD is related to exercise-induced wheezing (EIW), some proxy for EIA.MethodsJapanese version of the International Study of Asthma and Allergies in Childhood questionnaires were used. For 12,405 asthmatic school children, AD was defined as itchy rash coming and going for at least 6 months at any time in the last 12 months with affecting places of flexural parts of body, and severity of AD was rated according to frequency of being kept awake at night with the itch as follows: never in the past 12 months, less than one night per week and one or more nights per week.ResultsAdjusted for frequency of asthma attack, odds ratios (OR) of children with current AD as compared to those without AD for having EIW were 1.32 (95% confidence interval = 1.15–1.52), 1.35 (1.14–1.68) and 1.10 (0.92–1.31) for primary school, junior high school and high school children, respectively. EIW was more likely observed in accordance with increasing severity of AD in the primary school children with ORs of 1.12, 1.59 and 1.54 (p for trend < 0.01), and in the junior high school ones with ORs of 1.18, 1.31, 2.03 (<0.01), respectively.ConclusionsAD may be possibly related to EIW. Further studies investigating effect of AD treatment on EIW may be required.



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Interleukin 17A exacerbates ER-stress-mediated inflammation of macrophages following ICH

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Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Zhao Yang, Qingjun Liu, Hui Shi, Xuheng Jiang, Song Wang, Yuanlan Lu, Ji Zhang, Xiaofei Huang, Anyong Yu
IL-17A contributes to the initiation of inflammation following intracerebral hemorrhage (ICH). Endoplasmic reticulum (ER) stress acts on protein folding and contributes to inflammatory diseases. The role of IL-17A in the regulation of ER stress following ICH has not been well characterized. In this study, macrophages were stimulated with IL-17A, and then, ER stress and downstream pro-inflammatory factors were measured in vitro. In addition, brain edema and brain injury in ICH mice were assessed in vivo. We demonstrated that IL-17A induced ER stress in macrophages and thus promoted inflammation in vitro. Conversely, IL-17A inhibition attenuated ER stress and neuroinflammation. Furthermore, ERK 1/2 and p38 MAPK pathways mediated IL-17A-induced ER stress in macrophages. We also showed that IL-17A inhibition significantly attenuated ER stress and brain injury in ICH mice.In conclusion, our results demonstrate that IL 17A increases ER stress in macrophages and represents a novel mechanism in ICH.



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Seafood allergy: A comprehensive review of fish and shellfish allergens

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Publication date: Available online 30 May 2018
Source:Molecular Immunology
Author(s): Thimo Ruethers, Aya C. Taki, Elecia B. Johnston, Roni Nugraha, Thu T.K. Le, Tanja Kalic, Thomas R. McLean, Sandip D. Kamath, Andreas L. Lopata
Seafood refers to several distinct groups of edible aquatic animals including fish, crustacean, and mollusc. The two invertebrate groups of crustacean and mollusc are, for culinary reasons, often combined as shellfish but belong to two very different phyla. The evolutionary and taxonomic diversity of the various consumed seafood species poses a challenge in the identification and characterisation of the major and minor allergens critical for reliable diagnostics and therapeutic treatments. Many allergenic proteins are very different between these groups; however, some pan-allergens, including parvalbumin, tropomyosin and arginine kinase, seem to induce immunological and clinical cross-reactivity.This extensive review details the advances in the bio-molecular characterisation of 20 allergenic proteins within the three distinct seafood groups; fish, crustacean and molluscs. Furthermore, the structural and biochemical properties of the major allergens are described to highlight the immunological and subsequent clinical cross-reactivities. A comprehensive list of purified and recombinant allergens is provided, and the applications of component-resolved diagnostics and current therapeutic developments are discussed.



https://ift.tt/2H4XJ08

Interleukin 17A exacerbates ER-stress-mediated inflammation of macrophages following ICH

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Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Zhao Yang, Qingjun Liu, Hui Shi, Xuheng Jiang, Song Wang, Yuanlan Lu, Ji Zhang, Xiaofei Huang, Anyong Yu
IL-17A contributes to the initiation of inflammation following intracerebral hemorrhage (ICH). Endoplasmic reticulum (ER) stress acts on protein folding and contributes to inflammatory diseases. The role of IL-17A in the regulation of ER stress following ICH has not been well characterized. In this study, macrophages were stimulated with IL-17A, and then, ER stress and downstream pro-inflammatory factors were measured in vitro. In addition, brain edema and brain injury in ICH mice were assessed in vivo. We demonstrated that IL-17A induced ER stress in macrophages and thus promoted inflammation in vitro. Conversely, IL-17A inhibition attenuated ER stress and neuroinflammation. Furthermore, ERK 1/2 and p38 MAPK pathways mediated IL-17A-induced ER stress in macrophages. We also showed that IL-17A inhibition significantly attenuated ER stress and brain injury in ICH mice.In conclusion, our results demonstrate that IL 17A increases ER stress in macrophages and represents a novel mechanism in ICH.



https://ift.tt/2kDqJ6o

Seafood allergy: A comprehensive review of fish and shellfish allergens

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Publication date: Available online 30 May 2018
Source:Molecular Immunology
Author(s): Thimo Ruethers, Aya C. Taki, Elecia B. Johnston, Roni Nugraha, Thu T.K. Le, Tanja Kalic, Thomas R. McLean, Sandip D. Kamath, Andreas L. Lopata
Seafood refers to several distinct groups of edible aquatic animals including fish, crustacean, and mollusc. The two invertebrate groups of crustacean and mollusc are, for culinary reasons, often combined as shellfish but belong to two very different phyla. The evolutionary and taxonomic diversity of the various consumed seafood species poses a challenge in the identification and characterisation of the major and minor allergens critical for reliable diagnostics and therapeutic treatments. Many allergenic proteins are very different between these groups; however, some pan-allergens, including parvalbumin, tropomyosin and arginine kinase, seem to induce immunological and clinical cross-reactivity.This extensive review details the advances in the bio-molecular characterisation of 20 allergenic proteins within the three distinct seafood groups; fish, crustacean and molluscs. Furthermore, the structural and biochemical properties of the major allergens are described to highlight the immunological and subsequent clinical cross-reactivities. A comprehensive list of purified and recombinant allergens is provided, and the applications of component-resolved diagnostics and current therapeutic developments are discussed.



https://ift.tt/2H4XJ08

Potentially curable gastric adenocarcinoma treated without surgery

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Publication date: July 2018
Source:European Journal of Cancer, Volume 98
Author(s): Dilsa Mizrak Kaya, Graciela M. Nogueras-Gonzáles, Kazuto Harada, Fatemeh G. Amlashi, Irene Thomas, Jane E. Rogers, Manoop S. Bhutani, Jeffrey H. Lee, Brian Weston, Bruce D. Minsky, Jeannelyn S. Estrella, Mariela A. Blum Murphy, Aurelio Matamoros, Catherine E. Devine, Prajnan Das, Brian D. Badgwell, Jaffer A. Ajani
BackgroundSurgery is the best option for cure of localised gastric adenocarcinoma (GAC). When surgery is not possible due to comorbidities or patient choice, definitive chemoradiation is an option. We report on one of the largest cohorts of localised GAC patients who did not have surgery.MethodsWe identified 71 patients with localised GAC who received chemo/chemoradiation therapy but did not have surgery. We assessed various end-points: overall survival (OS), relapse-free survival (RFS), and clinical complete response (cCR; negative post therapy biopsy and no evidence of cancer by imaging).ResultsThe median follow-up time was 1.8 years (range; 0.4–10.6). Most of the patients were men (64.8%), and the median age was 73 years (range; 30–96). Reason for not having surgery included comorbidities in 34 (47.9%), poor performance status 14 (19.7%), and patient refusal 23 (32.4%). Of all 71 patients, a complete restaging evaluation with endoscopy and imaging could be performed for 50, and 32 (45.1%) achieved a cCR. For the entire cohort, the median OS was 2.1 years (95% confidence interval [CI] 1.78–2.55). The estimated OS rates at 2 and 5 years were 54% and 18%, respectively. Female gender (HR 0.39, 95% CI 0.16–0.98, p = 0.045) and chemoradiation (HR 0.25, 95% CI 0.06–1.01; p = 0.05) were independently associated with longer OS in the multivariate analysis.ConclusionOur data show that patients with localised GAC treated with chemotherapy and/or chemoradiation, who do not undergo surgery, have a 5-year OS rate of 18%.



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Organisational factors influencing early clinical trials enrollment: Gustave Roussy experience

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Publication date: July 2018
Source:European Journal of Cancer, Volume 98
Author(s): Sylvain Besle, Emilien Schultz, Antoine Hollebecque, Andreea Varga, Capucine Baldini, Patricia Martin, Sophie Postel-Vinay, Rastislav Bahleda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Eric Angevin, Jean-Pierre Armand, Vincent Ribrag, Jean-Charles Soria, Christophe Massard
PurposeEnrolment process influences the likelihood of patients' inclusion in early clinical trials (ECT) through social, medical and organisational factors.Patients and MethodsAll patients referred from 2008 to 2016 to the Drug Development Department (DITEP) of Gustave Roussy (GR) were reviewed. Referring physician, organisational factors, medical and socioeconomic characteristics for patients were analysed. Multivariate analysis was performed with regard to those factors. A telephone survey was conducted on a sample of referring physicians located outside GR (N = 142).ResultsBetween 2008 and 2016, 8694 requests were received with 49% from external physicians. Here, 4517 were male patients with a median age of 58 [49–66] years (range 18–85). Tumour types were gastrointestinal (28%), lung (19%), breast (9%) and gynaecologic (8%). Mean enrolment rate was 37% (ranging from 24 to 45%). From 2008 to 2016, the enrolment rate decreases from 39% to 24%. In the meantime, DITEP trials portfolio evolves with the part of precision medicine trials increase from 12% to 40%. Factors that were significantly associated with a lower likelihood of being enrolled were referral from an external physician (OR 0.15 s.16–0.21]) compared to a physician from DITEP and year of the request (2.74 [1.8–2.9] 2008 versus 2016). The enrolment rate and the number of patients addressed have a high variability regarding referring physicians, which is little explained by characteristics as training, previous experience or attitude regarding ECT.ConclusionBeyond patients' individual characteristics, we show that organisational and professional factors have a major impact on likelihood of enrolment in ECT.



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Effects of different photobiomodulation dosimetries on temporomandibular dysfunction: a randomized, double-blind, placebo-controlled clinical trial

Abstract

Changes involving temporomandibular joint, masticatory musculature, and associated structures characterize temporomandibular dysfunction (TMD). The analgesic and anti-inflammatory effect produced by photobiomodulation has contributed to pain relief and functional improvement. However, the parameters to be used have not yet been well established. The aim of this study is to compare the efficacy of three different photobiomodulation dosimetries in the treatment of patients with TMD. A randomized, double-blind, placebo-controlled clinical trial with 44 subjects divided into the groups 8 J/cm2 (n = 11), 60 J/cm2 (n = 11), 105 J/cm2 (n = 11), and control (n = 11). Pain, symptom severity, and joint mobility were evaluated before and after a ten-session protocol of photobiomodulation with AlGaAs laser (830 nm), at a power density of 30 mW/cm2. The mouth opening increased in the 8-J/cm2 group from 10.49 ± 4.68 to 15.40 ± 6.43 degrees, and in the right protrusion from 9.80 ± 4.2 to 12.56 ± 5.40 degrees after the intervention protocol (p < 0.05). All groups significantly decreased pain (p < 0.05). 830-nm laser photobiomodulation was effective in reducing TMD pain and symptoms at all doses tested. Only the doses of 8 J/cm2 were effective regarding maximal opening and protrusion of the mandible.



https://ift.tt/2L9GKvY

Evaluation of the effects of Er:YAG laser, Nd:YAG laser, and two different desensitizers on dentin permeability: in vitro study

Abstract

The purpose of this in vitro study was to evaluate and compare the efficacy of erbium-doped yttrium aluminum garnet (Er:YAG) laser, neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, PrevDent nano-hydroxyapatite toothpaste plus Repairing Serum Kit (PNH), and NUPRO Sensodyne Prophylaxis Paste with NovaMin (NPP) on dentin permeability reduction. Forty dentin discs obtained from bovine incisors were divided into four study groups: Er:YAG laser-treated (2940 nm; 0.2 W, 80 mJ/pulse, 3 Hz); Nd:YAG laser-treated (1064 nm; 1 W, 10 Hz); PNH-treated; and NPP-treated groups. The quantitative changes in permeability of each dentin disc were measured using a computerized fluid filtration method (CFFM) before and after desensitizer treatments. The data were analyzed using the Wilcoxon, paired-samples t, Kruskal-Wallis, and Mann-Whitney U tests. The dentin surfaces and tubules were also morphologically detected by scanning electron microscopy (SEM). In all groups, dentin permeability was significantly reduced after the desensitizer and laser treatments (p < 0.05). Among the groups, we detected a significant difference in only when comparing the Er:YAG laser- and NPP-treated groups (p = 0.034). SEM analysis revealed physical changes in the dentin surface in all groups. This in vitro study shows that all tested desensitizers and laser treatments reduced dentin permeability. Also, surface changes, such as complete or partial occlusion or shrinkage of dentin tubules, were observed in all groups. Although the laser groups performed best, the PNH protocol can be considered as an alternative therapeutic product. In addition, clinical and laboratory studies should be performed for this product, and their efficacy should be assessed by combined therapy with lasers.



https://ift.tt/2JhBBos

Helminth-induced regulatory T cells and suppression of allergic responses

Jayden Logan | Severine Navarro | Alex Loukas | Paul Giacomin

https://ift.tt/2Jk7lcv

Dendritic cells, T cells and lymphatics: dialogues in migration and beyond

Marc Permanyer | Berislav Bošnjak | Reinhold Förster

https://ift.tt/2JjjSwJ

Corrigendum to “Structure–activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures” [Bioorg. Med. Chem. 23 (2015) 1601–1612]

Publication date: Available online 30 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Shannon L. Nowotarski, Boobalan Pachaiyappan, Steven L. Holshouser, Craig J. Kutz, Youxuan Li, Yi Huang, Shiv K. Sharma, Robert A. Casero, Patrick M. Woster




https://ift.tt/2sjtn5m

Hydrothermal synthesis of a magnetic adsorbent from wasted iron mud for effective removal of heavy metals from smelting wastewater

Abstract

A magnetic adsorbent (MA) was synthesized from wasted iron mud of a groundwater treatment plant using a novel one-step hydrothermal method. The results showed that Fe content of MA was 41.8 wt%, 2.5 times higher than that of iron mud, which was caused by hydrothermal dissolution of non-ferrous impurities under alkaline condition, such as quartz and albite, regardless of addition of ascorbic acid or not. Ferrihydrite was 92.7% in dry iron mud before adding ascorbic acid and gradually decreased to 58.1% by increasing the molar ratio of ascorbic acid to Fe following hydrothermal treatment. The strongest saturation magnetization of 16.29 emu/g was observed in the prepared MA-4 when the ascorbic acid to Fe molar ratio was 1. The highest surface site concentration of 1.31 mmol/g was observed in MA-2 when the ratio was 0.02. The mechanism of hydrothermal conversion of wasted iron mud to MA was reductive dissolution of ferrihydrite to form siderite, which was then reoxidized to maghemite. When 12.5 g/L of MA-2 was applied to treat smelting wastewater, over 99% removal of Cu2+, Zn2+, Pb2+, and Cd2+ was achieved. The major mechanisms of Cu2+ and Zn2+ adsorption by the adsorbent were cationic exchange.



https://ift.tt/2sk1wlI

Study of zinc oxide nanoparticles and zinc chloride toxicity to annelid Enchytraeus crypticus in modified agar-based media

Abstract

Acute toxicity of zinc oxide nanoparticle (ZnO-NP, mean particle size diameter of 10 nm) powder and water-soluble salt of zinc (ZnCl2) to annelid Enchytraeus crypticus was tested using an agar-based nutrient-enriched medium with the addition of kaolin and humic acids (HA). Adults of the E. crypticus were cultivated in pure agar and in three types of modified exposure media containing different proportions of model soil constituents. Potworms were exposed to zinc in both forms (1–1000 mg kg−1 of agar) for 96 h. In experiments with ZnCl2, toxicity of zinc was the highest in pure agar followed by agar with HA and agar with kaolin and HA and the lowest toxicity was observed in agar with kaolin. The corresponding LC50 values were 13.2, 28.8, 39.4, and 75.4 mg kg−1 respectively. In contrast, zinc in the form of ZnO-NPs was most toxic in the presence of HA followed by pure agar, agar with kaolin, and kaolin with HA. In this case, LC50 values were 15.8, 43.5, 111, and 122 mg kg−1 respectively. Scanning electron microscopy revealed that the smallest agglomerates occurred in the presence of kaolin, where ZnO-NPs were sealed in a kaolin shell. This effect reduced the bioavailability and toxicity of the NPs. In contrast, larger agglomerates were observed in the presence of HA but a larger amount of zinc was dispersed in the volume of agar.



https://ift.tt/2IZI2wU

Pediatric Residents’ Assessment of Atopic Dermatitis Severity for Risk Assessment of Early Peanut Introduction,

Atopic dermatitis (AD), often referred to as eczema, is one of the most common skin disorders affecting the pediatric population.1 Although pediatricians diagnose eczema frequently, classification of severity can be challenging, as score-based indices (e.g., The Eczema and Area Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) index) are complicated and designed primarily for use in clinical trials. These instruments are used infrequently by general pediatricians and may be associated with discrepancies in AD classification between providers.

https://ift.tt/2IZFIpG

Development of Food Protein-Induced Enterocolitis Syndrome (FPIES) to egg following Immunoglobulin E (IgE)-mediated egg allergy,

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated condition characterized by repetitive vomiting 1-4 hours after ingestion of the particular food accompanied by additional symptoms such as lethargy, pallor or diarrhea.1 Atypical FPIES characterizes patients who are noted to have IgE-mediated sensitization to the FPIES-inducing food,2 and has been associated with an increased likelihood of persistent FPIES.3 A clinical conversion from an FPIES phenotype to an IgE-mediated phenotype to the same food has been described.

https://ift.tt/2spDFjG

Pilot study of the CAPS (Clinical extent, Area, Pruritus, Sleep) measure for atopic dermatitis severity,,✯✯✯,✯✯✯✯

Eczema; Atopic dermatitis; Outcome measures; Severity; Symptoms; ItchAbbreviations: AD, atopic dermatitis; BSA, body surface area; CAPS, Clinical extent, Area, Pruritus, Sleep; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator Global Assessment; POEM, Patient-Oriented Eczema Measure

https://ift.tt/2kAs5Pa

Telomere attrition is associated with declines in medial temporal lobe volume and white matter microstructure in functionally independent older adults

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Adam M. Staffaroni, Duygu Tosun, Jue Lin, Fanny M. Elahi, Kaitlin B. Casaletto, Matthew J. Wynn, Nihar Patel, John Neuhaus, Samantha M. Walters, Elissa S. Epel, Elizabeth H. Blackburn, Joel H. Kramer
Although leukocyte telomere length (TL) shortens over the lifespan and is associated with diseases of aging, little is known about the relationships between TL, memory, and brain structure. Sixty-nine functionally normal older adults (mean age = 71.7) were assessed at 2 time points (mean interval = 2.9 years). Linear mixed models assessed relationships between TL and hippocampal volume, fractional anisotropy, and mean diffusivity (MD) of the fornix and verbal and visual episodic memory. Unstandardized coefficients are reported in the following, and p values are not corrected for multiple comparisons. A negative baseline trend was observed between TL and fornix MD (b = −0.01, p = 0.06), but no other cross-sectional associations were significant (ps > 0.16). Greater TL shortening at follow-up was associated with greater hippocampal volume loss (b = 27.09, p < 0.001), even after controlling for global volume loss (b = 10.83, p = 0.002). Greater telomere attrition was also associated with larger increases in fornix MD (b = −0.01, p = 0.012) and decreases in fornix fractional anisotropy (b = 0.004, p = 0.002). TL was not associated with changes in episodic memory (ps > 0.23). These relationships may reflect neurobiological influences that affect both TL and brain structure, as well as the effect of TL on brain aging via mechanisms such as cellular senescence and inflammation.



https://ift.tt/2IXYmhJ

Do diurnal cortisol levels mediate the association between sleep disturbances and cognitive impairment?

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Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): José Haba-Rubio, Sami Ouanes, Yannick Franc, Pedro Marques-Vidal, Gerard Waeber, Peter Vollenweider, Armin von Gunten, Martin Preisig, Christine Kuehner, Enrique Castelao, Raphaël Heinzer, Julius Popp
Previous research found an association between sleep disturbances and cognitive deficits on the one hand, and between increased cortisol levels and poor cognitive performance on the other hand. We hypothesized that cortisol may, at least partially, mediate the link between sleep disturbances and cognitive impairment (CI). We analyzed data from 440 nondemented subjects aged ≥65 years (72.4 ± 4.5 years old, 55.7% women) participating at the population-based CoLaus/PsyCoLaus study, who underwent cognitive evaluation, complete polysomnography and cortisol measures during the day. Subjects with CI (N = 207, 47.05% of the sample) had lower sleep efficiency, less deep sleep (stage N3) and rapid eye movement sleep, and higher apnea/hypopnea index and oxygen desaturation index. After adjustment for possible confounders, oxygen desaturation index (≥4% and ≥6% per hour of sleep) were significantly associated with impaired cognitive performance. The results of Sobel's test for mediation using the regressions between the sleep-related variables and cortisol values, and between the cortisol and the Clinical Dementia Rating score were not significant (all p > 0.05). Our data suggest that sleep-disordered breathing is associated with CI, but that this association is not mediated by increased diurnal cortisol levels.



https://ift.tt/2H3eWac

Sexual assault interventions may be doing more harm than good with high-risk males

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Publication date: Available online 30 May 2018
Source:Aggression and Violent Behavior
Author(s): Neil Malamuth, Mark Huppin, Daniel Linz
Based on legal requirements and other considerations, there have been many well-meaning interventions intended to reduce sexual assault on university campuses throughout the US. There is no legal requirement, however, to evaluate the effectiveness of these programs, and few evaluations have been conducted. Those that have suggest that at best only a small number of these interventions have been effective and those involve bystander interventions. More importantly, there has been very little research examining the effects of such interventions on men at high risk for sexual aggression, who presumably are a key target of such interventions. Research on similar campaigns in other domains should have alerted investigators to the possibility of boomerang reactance effects wherein interventions can actually have the opposite of the intended effects for high-risk college males. The few studies that directly have examined this possibility indeed are supportive of the substantial likelihood of such negative effects. Commonly used interventions may fail with high-risk men because they are likely to generate "hostility reactance" — one of the key causes of both sexual violence itself and the unintended adverse effects of the interventions. We raise the question of why universities have failed to address this possible effect of interventions and why previous reviews have not highlighted this possible danger.



https://ift.tt/2IZalvy

Different Treatments With the TRV Reposition Chair

Condition:   Benign Paroxysmal Positional Vertigo
Intervention:   Procedure: Type of repositional maneuvre
Sponsor:   Aalborg Universitetshospital
Recruiting

https://ift.tt/2skyW3H

Audit of the Spanish EURECCA Esophagogastric Cancer Registry

Conditions:   Cancer of Stomach;   Cancer of Esophagus
Intervention:  
Sponsor:   Parc de Salut Mar
Not yet recruiting

https://ift.tt/2xu0Lvo

Thykamine Safety and Efficacy Study in Mild-to-Moderate Atopic Dermatitis

Condition:   Atopic Dermatitis Eczema
Interventions:   Drug: Administration of Placebo;   Drug: Administration of PUR0110 (Thykamine) 0.05%;   Drug: Administration of PUR0110 (Thykamine) 0.1%;   Drug: Administration of PUR0110 (Thykamine) 0.25%
Sponsor:   PurGenesis Technologies Inc.
Recruiting

https://ift.tt/2skyVNb

ctDNA as a Biomarker for Treatment Response in HNSCC

Condition:   Carcinoma, Squamous Cell of Head and Neck
Intervention:   Other: Blood draw
Sponsor:   The Netherlands Cancer Institute
Not yet recruiting

https://ift.tt/2xsYW1J

Re: “High Thyroid Cancer Mortality Rate in Japan: A Result of Non-aggressive Treatment Strategy, or Just an Aging Population?” By Magner (Thyroid [Epub ahead of print]; DOI: 10.1089/thy.2018.0121)

Thyroid, Ahead of Print.


https://ift.tt/2IWMr3U

No-Scar Transoral Thyroglossal Duct Cyst Excision in Children

Thyroid, Ahead of Print.


https://ift.tt/2H5yRoS

Different Treatments With the TRV Reposition Chair

Condition:   Benign Paroxysmal Positional Vertigo
Intervention:   Procedure: Type of repositional maneuvre
Sponsor:   Aalborg Universitetshospital
Recruiting

https://ift.tt/2skyW3H

Audit of the Spanish EURECCA Esophagogastric Cancer Registry

Conditions:   Cancer of Stomach;   Cancer of Esophagus
Intervention:  
Sponsor:   Parc de Salut Mar
Not yet recruiting

https://ift.tt/2xu0Lvo

Thykamine Safety and Efficacy Study in Mild-to-Moderate Atopic Dermatitis

Condition:   Atopic Dermatitis Eczema
Interventions:   Drug: Administration of Placebo;   Drug: Administration of PUR0110 (Thykamine) 0.05%;   Drug: Administration of PUR0110 (Thykamine) 0.1%;   Drug: Administration of PUR0110 (Thykamine) 0.25%
Sponsor:   PurGenesis Technologies Inc.
Recruiting

https://ift.tt/2skyVNb

ctDNA as a Biomarker for Treatment Response in HNSCC

Condition:   Carcinoma, Squamous Cell of Head and Neck
Intervention:   Other: Blood draw
Sponsor:   The Netherlands Cancer Institute
Not yet recruiting

https://ift.tt/2xsYW1J

Ecological quality status evaluation of a monsoonal tropical estuary using benthic indices: comparison via a seasonal approach

Abstract

The use of biotic indices has garnered attention during the last decade due to its extensive application in evaluating ecological quality status (EcoQS) of marine waters and estuaries. Three seasonal surveys were conducted in the Kundalika estuary, India to evaluate the ecostatus using five benthic indices and comparing their effectiveness considering the estuarine salinity gradient and seasonality. All indices gave divergent results displaying a wide range of classes (good to bad) across salinity zones and seasons. Comparatively, M-AMBI discriminated the EcoQS suitably than other indices. Hence, a seasonally averaged approach for M-AMBI was proposed to obtain a final mean EcoQS which assigned moderate status to the euhaline and poly-mesohaline zones and poor status to the oligohaline zone. Considering the high degree of spatial heterogeneity and seasonality in the estuary, the monsoon data was found to lower the EcoQS due to natural stress in some cases; the exclusion of the monsoon season resulted in a more valid ecostatus. Therefore, this approach which combines information from the non-monsoon seasons stands out in providing a useful basis for ecological management by scrutinizing responses of macrobenthos. Also, we suggest salinity zone-wise evaluation for more effective classification chiefly in tropical monsoonal estuaries. An effort to establish a final EcoQS was performed; however, future in-depth studies are necessary to ascertain the reliability of the successful biotic index (M-AMBI) in estuaries with different stressors.



https://ift.tt/2J3OsqT

Seasonal variations of contamination and exoskeletal malformations in the white shrimps Palaemon longirostris in the Gironde estuary, France

Abstract

Since the end of the 1980s, white shrimps (Palaemon longirostris) from the Gironde estuary have exhibited exoskeletal malformations, mainly involving cephalothorax, rostrum, scaphocerites and uropods. An 8-month study was carried out in 2015. Each month, 200 individuals were sampled and examined for exoskeletal malformations. Temporal variations in malformation frequency were noted, particularly during the breeding period, along with decreases in the size of non-deformed shrimps related to the appearance of juveniles in breeding sites, and high mortality among deformed shrimps. A significant increase in proportions of deformed shrimp was observed, relating particularly to the size (and therefore the age) of individuals. No significant difference was found between shrimp proportions with different numbers of malformations (one to four) for a fixed size class, nor was there any variation in proportions within different size classes for a fixed number of malformations. This would appear to indicate that the number of malformations is acquired and new malformations do not seem to appear during the life cycle, except for the smallest (youngest) shrimps. The malformation spectrum showed no significant differences between the biggest and smallest individuals for the different malformation associations, except for those involving cephalothorax, rostrum and uropods. This would suggest that some malformation associations lead to a higher mortality rate in shrimps subjected to them, due to greater impairment of feeding and/or swimming behaviour. Multiple component analysis of the different types of malformation showed correlations between exoskeletal pieces (rostrum and cephalothorax) and appendixes (scaphocerites and uropods). Regarding metal contamination in shrimp, no significant difference was highlighted between deformed and non-deformed shrimps. Organic pollutants were not measured in tissues. Certain herbicides such as metolachlore and chlortoluron were detected at high concentrations in the Gironde estuary during the breeding period corresponding to the higher occurrence of exoskeletal malformations.



https://ift.tt/2LLHhFJ

Impact of Franseen needle on rapid onsite evaluation and histological examination following endoscopic ultrasonography-guided tissue acquisition in patients with splenic malignant lymphoma

Publication date: Available online 30 May 2018
Source:Arab Journal of Gastroenterology
Author(s): Tesshin Ban, Hiroshi Kawakami, Yoshimasa Kubota, Yuichiro Sato
Rapid onsite evaluation (ROSE) following endoscopic ultrasonography (EUS)-guided fine-needle aspiration contributes to the establishment of a diagnosis for various organs. Newly designed three-plane symmetric needles for EUS-guided fine-needle biopsy (EUS-FNB), such as the Franseen needle, have been developed to enable histological core tissue acquisition. However, EUS-guided tissue acquisition for hypervascular splenic lesions remains challenging. Tissue acquisition in cases of splenic malignant lymphoma by using a conventional needle with multiple strokes and suction may result in indeterminate ROSE due to blood contamination and tiny fragments of lymphoma tissue, whereas EUS-FNB by using the Franseen needle with a minimal number of strokes with suction demonstrates qualified specimens for the ROSE as well as histological examination. For splenic malignant lymphomas, EUS-FNB by using the Franseen needle with a limited number of strokes may facilitate qualified specimen acquisition.



https://ift.tt/2J6100L

The impact of cold on the respiratory tract and its consequences to respiratory health

The increasing use, and sometimes the abuse, particularly in industrialized countries of air conditioning at home, in car, hotel and shopping centres has highlighted new emerging public health issues, resultin...

https://ift.tt/2Lb4MXE

Heptamer Peptide Disassembles Native Amyloid in Human Plasma Through Heat Shock Protein 70

Rejuvenation Research, Ahead of Print.


https://ift.tt/2skPUyO

3D-Printed Poly(ɛ-caprolactone)/Graphene Scaffolds Activated with P1-Latex Protein for Bone Regeneration

3D Printing and Additive Manufacturing, Ahead of Print.


https://ift.tt/2LJXxXu

Effective shell wall thickness of vertically aligned ZnO-ZnS core-shell nanorod arrays on visible photocatalytic and photo sensing properties

Publication date: 5 December 2018
Source:Applied Catalysis B: Environmental, Volume 237
Author(s): Kugalur Shanmugam Ranjith, Rutely Burgos Castillo, Mika Sillanpaa, Ramasamy Thangavelu Rajendra Kumar
Development of hierarchical core-shell semiconductor heterostructures ensue significant advancement in catalytic functional structures with improvised optical functionalities. Shell wall controlled vertically aligned ZnO-ZnS core-shell nanorod (NR) heterostructures were grown on transparent conductive substrates along the c-axis by sulfidation of aligned ZnO nanorod arrays for visible photocatalytic properties. The effects of the sulfidation time on the morphology, crystalline properties, optical property, photocurrent response, and photocatalytic activity of the catalyst arrays were studied under UV and visible light irradiation. The shell wall thickness of these heterostructures influenced in great extent the effective photo responsive charge separation and improved carrier mobility. ZnO-ZnS core-shell heterostructure having the shell wall thickness of 20 nm has exhibited more efficient visible photocatalytic behavior due to effective separation of carriers and improved visible absorption. On further increasing the wall thickness the catalytic efficiency was reduced due to the poor carrier (hole) mobility in the polycrystalline shell grains which induced the higher recombination rate. Stability and reusability of ZnO-ZnS core-shell nanostructures reveals that the ZnS acted as a protective layer over the ZnO NR arrays. In appraisal with ZnO NR arrays, the control over the shell wall thickness of ZnO-ZnS core-shell NR array attributed to the excellent visible photocatalytic activity and improvised absorption of light in visible region at ZnO-ZnS interface and effective separation of photogenerated electron-hole pairs at ZnO-ZnS heterojunctions.

Graphical abstract

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https://ift.tt/2IY3McG

Improving active biomonitoring in aquatic environments: The optimal number and position of moss bags

Publication date: October 2018
Source:Ecological Indicators, Volume 93
Author(s): S. Debén, J.A. Fernández, A. Carballeira, G. Kosior, J.R. Aboal
The present study was carried out to determine the optimal number of moss bags of Fontinalis antipyretica required for biomonitoring stream water pollutants. With this aim, we examined the variability in the concentrations of Al, Cd, Co, Cu, Fe, Ni, Pb and Zn in 50 moss bags exposed in 4 different stream sampling sites (SS). In general, there were no significant differences in the element concentrations between groups of moss bags (n = 5), either along the 50 m length of each stream, or between the different sides of the streams. Considering errors of 10, 15 and 20%, the maximum number of moss bags required to estimate the mean tissue concentrations of the elements at the SS was respectively 26, 11 and 6. For most of the pairs of SS and elements studied, 5 or fewer moss bags were sufficient to differentiate between the mean concentrations. These findings allow us to conclude that a greater number of moss bags (at least 6) than those generally used until present should be utilized for biomonitoring water pollution with aquatic bryophytes.

Graphical abstract

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https://ift.tt/2srkPZo

A rapidly room-temperature-synthesized Cd/ZnS:Cu nanocrystal photocatalyst for highly efficient solar-light-powered CO2 reduction

Publication date: 5 December 2018
Source:Applied Catalysis B: Environmental, Volume 237
Author(s): Xianguang Meng, Guifu Zuo, Peixiao Zong, Hong Pang, Jian Ren, Xiongfeng Zeng, Shanshan Liu, Yi Shen, Wei Zhou, Jinhua Ye
An ideal photocatalyst that can promisingly convert CO2 should have suitable band gap and fully consider the activation of reaction. However, well-designed photocatalytic materials with these aspects are very limited. This study reports a highly efficient CO2 reduction photocatalyst based on ZnS nanocrystals which can be rapidly synthesized at room temperature and operated under solar light irradiation at all-inorganic reaction system. Two functional elements, Cu and Cd, are respectively used as dopant and cocatalyst of ZnS nanocrystal for selective CO2 reduction. Cu+ doping expands the photoabsorption of ZnS into visible light region and the simultaneous Cd2+ surface modification significantly improves the activity of CO2 reduction with 99% formic acid selectivity. A combination of charge density distribution and electronic state studies reveal that the Cd s orbital displays obviously higher density of states near band-edge with a relatively lower lying band center than that of Zn s orbital. This will greatly favor the charge transfer from conduction band of ZnS to the surface state created by Cd2+ for catalyzing CO2 reduction.

Graphical abstract

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Monophasic Synovial Sarcoma of Tongue: A Rarest of Rare Case Scenario

Abstract

Synovial sarcoma is a rare tumour of head and neck. Primary synovial sarcoma of tongue is very uncommon. Based on morphology, it can be classified as classical biphasic variant, monophasic spindle cell variant, monophasic epithelial variant and poorly differentiated variant. The authors with an index case of 74 year old lady with monophasic spindle cell synovial sarcoma of oral tongue which is one of the rarest variants (our case is the 15th case reported of synovial sarcoma of the tongue and only the 3rd case in the world which had a monophasic histopathologic pattern) studied the morphology and described the disease entity in detail. She was treated with wide local excision of sarcoma followed by adjuvant radiotherapy.



https://ift.tt/2kAYp4o

Robot Assisted Trans Axillary Thyroidectomy: A Subcontinent Experience



https://ift.tt/2spjzWM

Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer

Background/Aim: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Patients and Methods: Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Results: Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. Conclusion: EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals.



https://ift.tt/2kAUYuw

Potentially Malignant Oral Disorders and Cancer Transformation

Cancer in the oral cavity is often preceded by precursor lesions. Nine oral mucosal disorders are known to have an increased risk of malignant transformation. The etiology varies from disorders caused by exogenous factors such as tobacco and autoimmune inflammation to idiopathic or inherited genetic aberrations. In this review, these potentially malignant disorders (PMDs) are described regarding clinical presentation and histopathological architecture. Special attention is paid to the underlying etiologies of PMDs and the potential pathways leading to cancer. The clinical perspective focuses on the importance of accurate and timely diagnosis.



https://ift.tt/2srlD0j

Significance of Age in Japanese Patients Receiving Sunitinib as First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: Comparative Assessment of Efficacy and Safety between Patients Aged =75 Years

Background/Aim: To date, it has not been well characterized whether sunitinib is effective in elderly patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to investigate the impact of age on clinical outcomes of mRCC patients receiving sunitinib. Patients and Methods: The efficacy and safety of first-line sunitinib in 154 consecutive mRCC patients were retrospectively compared between patients aged <75 (n=125) and ≥75 (n=29) years. Results: There were no significant differences in the major clinicopathological characteristics between younger and older patients; however, the reduction of the initial dose of sunitinib was significantly more frequent in older than younger patients. No significant difference in response rate, clinical benefit rate or proportion of patients going on to receive second-line therapy was noted between these two groups. Furthermore, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, and no significant impact of age on PFS or OS was documented by the Cox proportional hazards regression analyses. Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients. Although there was no significant difference in the incidence of dose reduction or discontinuation of sunitinib between the two groups, the interruption of sunitinib was more frequently required in older than younger patients. Conclusion: These findings suggest that advanced age alone should not be regarded as a contraindication to the introduction of sunitinib as first-line systemic therapy for mRCC patients.



https://ift.tt/2IXoBVH

Multimodal Anti-tumor Approaches Combined with Immunotherapy to Overcome Tumor Resistance in Esophageal and Gastric Cancer

Upper gastrointestinal malignancies are associated with a high disease burden worldwide, and esophageal and gastric cancers represent the most common entities. Given a lack of early characteristic symptoms and potent screening instruments, the majority of patients present with advanced disease at the time of diagnosis. Complete surgical resection is a first-line curative option, and multimodal approaches involving chemotherapy and radiotherapy further improve patient prognosis. However, response to standard adjuvant and neoadjuvant treatments remains low, and new strategies are warranted to increase tumor control rates. Immunotherapy is emerging in various cancer entities and may be successfully combined with standard therapeutic regimens to improve patient outcome. For the purpose of this review we aimed to assess combined approaches of immunotherapy and standard treatment options such as chemotherapy, radiotherapy and surgery. Current trials evaluating multimodal approaches with immunotherapy in esophageal and gastric cancer are evaluated.



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Second Primary Malignancies in Patients with Well-differentiated/Dedifferentiated Liposarcoma

Background: Well-differentiated/dedifferentiated (WD/DD) liposarcoma is a rare malignancy of putative adipocyte origin. To our knowledge, there have only been isolated case reports describing second primary cancer in patients with this disease. We report on a combined case series of such patients and explore the frequency of this occurrence using a national cancer database. Materials and Methods: Demographics and clinicopathological data were collected from patients with WD/DD liposarcoma who were found to have a concurrent or subsequent second primary cancer, at one of three sarcoma referral centers from 2014-2016. The Surveillance, Epidemiology and End Results (SEER) database was also queried to identify adult patients diagnosed with WD/DD liposarcoma between 1973-2012. Observed/expected (O/E) ratios of second primary malignancies among these cases were calculated by comparison to the age-adjusted cancer incidence in the general population using SEER*stat software. Results: In total, 26 out of 312 consecutive patients (8.3%) with WD/DD liposarcoma at our centers had a second primary cancer identified within 2 years of liposarcoma diagnosis. In the SEER database, among 1,845 patients with WD/DD liposarcoma, 75 (4.1%) had a second cancer within 2 years after liposarcoma diagnosis (O/E ratio=1.81, 99% confidence interval(CI)=1.33-2.40). Patients less than 50 years old at the time of liposarcoma diagnosis had a higher O/E ratio for second primary malignancy compared to older patients. A total of 269 patients (14.6%) developed a second cancer (O/E=1.33, 99% CI=1.15-1.54). Conclusion: In some patients with WD/DD liposarcoma, there appears to be an increased risk of having a second primary cancer. Further validation and investigation is needed, as this finding may have implications (e.g. closer screening) for patients with this disease.



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Hyperfractionated or Accelerated Hyperfractionated Re-irradiation with >=42 Gy in Combination with Paclitaxel for Secondary/Recurrent Head-and-Neck Cancer

Background/Aim: Patients with secondary/ recurrent squamous cell head and neck cancer (SCCHN) have poor prognoses. Outcomes of re-irradiation with ≥42 Gy plus paclitaxel for secondary/recurrent SCCHN are herein presented. Patients and Methods: Two patients re-irradiated for secondary/recurrent SCCHN were evaluated. Patients received 44.4 Gy (2x1.2 Gy/day) or 42.0 Gy (2x1.5 Gy/day), respectively, plus concurrent paclitaxel (35 mg/m2 weekly or 20 mg/m2 twice per week). Results: One patient developed a locoregional recurrence and additional metastases at 12 months after re-irradiation and died at 13 months. The other patient developed multiple bone metastases at 103 months and died at 104 months. Acute toxicities included grade 2 anemia and mucositis in both patients. Radiation dermatitis was grade 2 in one patient and grade 3 in the other. Conclusion: Re-irradiation with 42.0-44.4 Gy given twice daily plus paclitaxel was well tolerated and achieved a favorable response. The results need to be confirmed in a prospective trial.



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Specifically Targeted Electromagnetic Fields Arrest Proliferation of Glioblastoma Multiforme U-87 Cells in Culture

Background/Aim: Glioblastoma multiforme is an aggressive primary tumor that arises in the glial cells of the brain. Standardized first-line treatment has considerable morbidity and less than one-year median survival after intervention. Ultra-low intensity electromagnetic fields have been shown to interact with biological organisms without anticipated deleterious side-effects. The aim of the study was to determine if a novel, non-invasive application of non-ionizing radiation has an inhibitory effect on proliferation of glioblastoma multiforme cells. Materials and Methods: U-87 MG cells were continuously exposed for 54 h to an electromagnetic field tuned to simultaneously interact with DNA/RNA oligonucleotides (mutated alpha-kinase 2 gene/Hsa-miR-381-5p respectively) and proteins (HSP70/CHI3L1). Results: Exposed cells demonstrated a significant inhibition of cell growth and concurrent increase in cell death. Conclusion: This technology induces cell death by novel non-cytotoxic mechanisms unlikely to induce side-effects in patients; can be customized for individual tumors and may contribute to the emerging strategy of personalized medicine.



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Renal Cell Carcinoma, Unclassified with Medullary Phenotype and Synchronous Renal Clear Cell Carcinoma Present in a Patient with No Sickle Cell Trait/Disease: Diagnostic and Therapeutic Challenges

Renal medullary carcinoma (RMC) is an aggressive high-grade renal cell carcinoma (RCC) associated almost exclusively with sickle cell trait or sickle cell disease. However, RCC with RMC features has rarely been reported in patients with no sickle cell trait or disease. Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is a newly-coined term used by an international panel of experts to describe renal cell carcinoma showing morphologic and immunohistochemical features of renal medullary carcinoma in patients without sickle cell trait/disease. So far, only one study in the English literature has described five such cases. Here, we report a case with unique clinical and pathological features in a 76-year-old male patient without sickle cell trait. The patient had a history of colon cancer with liver and lung metastases and was found to have a new renal mass in his right kidney during the follow up. A right nephrectomy was performed and showed two separate masses (tumor 1 and tumor 2). Tumor 1 had histologic features of RMC and the tumor cells were positive for CK7, Pax8, and OCT4 and showed loss of nuclear INI1 expression. Tumor 1 was diagnosed as RCCU-MP (6.3 cm, pT3aNx, WHO/ISUP nuclear grade 3). Tumor 2 showed features of clear cell type of RCC (0.6 cm, pT1aNx, WHO/ISUP grade 2) with intact nuclear INI1 expression. Three-months post-nephrectomy, the patient developed lung metastasis of RCCU-MP. To the best of our knowledge, this was the first documented case with synchronous RCCU-MP and clear cell RCC presenting in a patient without sickle cell trait. Careful histologic assessment with a panel of immunohistochemical biomarkers was helpful to render a correct diagnosis for early aggressive treatment.



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Moesin Up-regulation Is Associated with Enhanced Tumor Progression Imaged Non-invasively in an Orthotopic Mouse Model of Human Glioblastoma

Background/Aim: Glioblastoma is a recalcitrant and poorly understood disease. The aim of the present study was to investigate the effect of moesin up-regulation on tumor progression in an orthotopic nude-mouse model of human glioblastoma. Materials and Methods: U87-GFP glioblastoma cells, transfected with either U87-H4645 (moesin up-regulated) or U87-H149 (vector control) were orthotopically implanted into the brains of nude mice. Moesin expression in the tumors was analyzed with RT-PCR and western blotting. Real-time fluorescence imaging was used to longitudinally and non-invasively quantitate tumor growth. The expression of cancer-related genes β-catenin, CD44, MMP-2, ICAM-1, and PCNA in the tumor was analyzed by RT-PCR, western blotting and immunohistochemistry in both sublines. Results: The expression levels of moesin mRNA and protein were significantly increased in the glioblastoma derived from transfected U87-H4645 cells compared to the vector control and untransfected cells. Tumor growth rate and final tumor weight were significantly increased in the animals with the glioblastoma derived from transfected U87-H4645 cells, compared to untransfected and vector control (p<0.01). mRNA expression of β-catenin, CD44, ICAM-1, and MMP-2 in the glioblastoma derived from the transfected U87-H4645 tumors was significantly increased compared with tumors derived from untransfected and vector-control U87 cells (p<0.01). Furthermore, a similar increase in the expression of these proteins was observed by western blotting or immunohistochemistry. Conclusion: Up-regulation of moesin expression in glioblastoma cells resulted in more aggressive orthotopic glioblastoma growth in nude mice. This effect may be mediated by the regulation of several proliferation-, adhesion-, and invasion-related cancer genes, which may serve as future therapeutic targets for this recalcitrant disease.



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Impact of Pleural Effusion on Outcomes of Patients Receiving Osimertinib for NSCLC Harboring EGFR T790M

Background/Aim: Osimertinib has demonstrated promising efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC). We investigated the efficacy of osimertinib in such patients presenting with pleural effusion, which has been unclear to date. Patients and Methods: The medical records of all patients treated with osimertinib for advanced NSCLC with EGFR T790M between April 2016 and July 2017 at our Institution were retrospectively reviewed. Time to treatment failure (TTF) and overall survival (OS) were determined as endpoints. Results: Twenty-three patients (seven with pleural effusions) were treated with osimertinib. Patients with pleural effusion had significantly shorter median TTF than those without (3.7 vs. 12.8 months, respectively, p=0.021), as well as shorter median OS (7.8 months vs. not attained, respectively, p=0.002). Metastasis to the brain, bone, and liver did not significantly influence our endpoints. Conclusion: Osimertinib monotherapy is less effective in patients with NSCLC with pleural effusions.



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An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells

Background/Aim: EPH receptor A2 (EPHA2) is highly expressed in aggressive types of human cancer, and is expected to be an excellent target molecule for antibody treatments. In this study, we investigated the therapeutic potential of antibody to EPHA2 against melanoma in vitro. Materials and Methods: We generated three monoclonal antibodies (mAbs) to EPHA2 and examined cell-surface expression by flow cytometry. To investigate the ability to inhibit tumor cell migration therapy with mAbs to EPHA2, we performed a wound scratch assay and invasion assay. We investigated the therapeutic effects of immunotoxins consisting of toxin-conjugated EPHA2 mAbs. Results: All human melanoma cell lines studied expressed EPHA2. Like natural ligand ephrin-A1, one of EPHA2 mAbs, SHM16, inhibited metastatic behavior of cells, such as migration and invasion. In addition, drastic growth inhibition and cytotoxicity were found using immunotoxin-conjugated SHM16. Conclusion: These observations indicate a promising role for EPHA2 as a target in antibody treatments for melanoma, and demonstrate the potential therapeutic effects of an agonistic antibody to EPHA2.



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Neoadjuvant Platinum-based Chemotherapy Followed by Radical Hysterectomy for Stage Ib2-IIb Adenocarcinoma of the Uterine Cervix - An Italian Multicenter Retrospective Study

Aim: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. Patients and Methods: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). Results: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. Conclusion: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix.



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Usefulness of Preoperative 18F-FDG-PET in Detecting Invasive Intraductal Papillary Neoplasm of the Bile Duct

Background/Aim: Preoperative identification of the invasive component remains challenging in intraductal papillary neoplasm of the bile duct (IPNB). We evaluated the ability of preoperative 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) to differentiate between non-invasive IPNB, invasive IPNB, and papillary cholangiocarcinoma (CCA). Patients and Methods: The maximum standardized uptake values (SUVmax) of 11 patients with IPNB (6 non-invasive and 5 invasive) and 20 with papillary CCA who underwent pre-surgical 18F-FDG-PET were assessed. The SUVmax cut-off that predicts an invasive component was determined using receiver operating characteristic (ROC) curve analysis. Results: The SUVmax in patients with invasive IPNB and papillary CCA were significantly higher than in patients with non-invasive IPNB (p=0.035 and 0.0025, respectively). ROC curve analysis revealed an optimal SUVmax cut-off of 4.5, which had 94.5% accuracy, 76.0% sensitivity, and 100% specificity. Conclusion: Our data suggest that the preoperative 18F-FDG-PET SUVmax can differentiate non-invasive IPNB from invasive IPNB and papillary CCA.



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Radiological Features of Brain Metastases from Non-small Cell Lung Cancer Harboring EGFR Mutation

Aim: To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Patients and Methods: Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT. Results: Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037). Conclusion: Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain.



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Hapalindole H Induces Apoptosis as an Inhibitor of NF-ĸB and Affects the Intrinsic Mitochondrial Pathway in PC-3 Androgen-insensitive Prostate Cancer Cells

Background: Prostate cancer presents the highest incidence rates among all cancers in men. Hapalindole H (Hap H), isolated from Fischerella muscicola (UTEX strain number LB1829) as part of our natural product anticancer drug discovery program, was found to be significantly active against prostate cancer cells. Materials and Methods: In this study, Hap H was tested for nuclear factor-kappa B (NF-ĸB) inhibition and selective cytotoxic activity against different cancer cell lines. The apoptotic effect was assessed on PC-3 prostate cancer cells by fluorescence-activated cell sorting analysis. The underlying mechanism that induced apoptosis was studied and the effect of Hap H on mitochondria was evaluated and characterized using western blot and flow cytometric analysis. Results: Hap H was identified as a potent NF-ĸB inhibitor (0.76 μM) with selective cytotoxicity against the PC-3 prostate cancer cell line (0.02 μM). The apoptotic effect was studied on PC-3 cells. The results showed that treatment of PC-3 cells with Hap H reduced the formation of NAD(P)H, suggesting that the function of the outer mitochondrial membrane was negatively affected. Thus, the mitochondrial transmembrane potential was assessed in Hap H treated cells. The results showed that the outer mitochondrial membrane was disrupted as an increased amount of JC-1 monomers were detected in treated cells (78.3%) when compared to untreated cells (10.1%), also suggesting that a large number of treated cells went into an apoptotic state. Conclusion: Hap H was found to have potent NF-ĸB p65-inhibitory activity and induced apoptosis through the intrinsic mitochondrial pathway in hormone-independent PC-3 prostate cancer cells.



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Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab with Maintenance Bevacizumab as a First-line Treatment for Advanced Non-squamous Non-small Cell Lung Cancer in Elderly Patients

Background/Aim: The combination of platinum-doublet chemotherapy with bevacizumab has been established as a first-line treatment option in non-elderly patients with non-squamous (non-sq) non-small cell lung cancer (NSCLC). However, the safety and efficacy of this regimen have not yet been fully established in elderly patients. Patients and Methods: Chemo-naïve patients with non-sq NSCLC, aged ≥75 years, having a good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were considered eligible. Patients received carboplatin (area under the curve=5 mg/ml/min), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) every 3 weeks for up to 4 cycles, followed by maintenance bevacizumab. The primary endpoint was the objective response rate (ORR; target=50%, threshold=30%; Simon's two-stage design), and the secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). Results: Twelve patients were enrolled from June 2013 to July 2017. The study was closed because of slow patient accrual. The median patient age was 80 years. Eleven patients (92%) completed 4 cycles of induction chemotherapy. Seven patients achieved a partial response (PR), yielding an ORR of 58%. The median PFS was 8.4 [95% confidence interval (CI)=4.4-10.5] months, and the median OS was 33.9 (95%CI=13.2-43.3) months. Toxicities were generally mild and consistent with previous reports. There were no treatment-related deaths. Conclusion: A regimen comprising carboplatin and pemetrexed plus bevacizumab followed by maintenance bevacizumab is feasible and potentially efficacious in elderly patients with non-sq NSCLC.



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MiR-193a-5p and -3p Play a Distinct Role in Gastric Cancer: miR-193a-3p Suppresses Gastric Cancer Cell Growth by Targeting ETS1 and CCND1

Background/Aim: MicroRNAs (miRNAs) are small non-protein-coding RNAs, that can be generated from the 5p or 3p arm of precursor miRNA (pre-miRNA). Differential miRNA arm selection has been reported between tumor and normal tissue in many cancer types; however, the biological function and mechanism of miRNA arm switching in gastric cancer remain unclear. Materials and Methods: Profiles of miRNA expression in gastric cancer were obtained from The Cancer Genome Atlas (TCGA). The biological role of miR-193a-5p/-3p in tumor growth and invasive abilities was assessed through a gain-of-function approach. Target genes of miR-193a-3p were identified using bioinformatics and an experimental approach. Results: The expression levels of miR-193a-5p, and not of miR-193a-3p, were significantly decreased in gastric cancer compared to adjacent normal tissues. Ectopic expressions of miR-193a-5p and miR-193a-3p revealed that they both inhibited gastric cancer cell growth, but only miR-193a-3p significantly suppressed cell invasion ability. Using a bioinformatics approach, we identified 18 putative target genes of miR-193a-3p. Both mRNA and protein levels of cyclin D1 (CCND1) and ETS proto-oncogene 1 (ETS1) were significantly decreased in AGS cells transfected with miR-193a-3p mimics. ETS1 or CCND1 knockdown significantly suppressed gastric cancer cell growth, similar to miR-193a-3p overexpression. Conclusion: Our results indicated that miR-193a-3p suppressed gastric growth and motility, at least partly, by directly targeting CCND1 and ETS1 expression.



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A review on the ethnomedicinal uses, phytochemistry and pharmacology of Alpinia officinarum Hance

Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Ibrahim Babangida Abubakar, Ibrahim Malami, Yakubu Yahaya, Sahabi Manga Sule
Ethnopharmacological relevanceAlpinia officinarum Hance is a perennial plant that has been traditionally used for many decades to treat several ailments including inflammation, pain, stomach-ache, cold, amongst others. Pharmacological studies over the years have demonstrated remarkable bioactivities that could be further explored for development of new therapeutic agents against various ailments.Aim of the studyThe paper critically reviewed the ethno-medicinal uses, pharmacology, and phytochemistry of A. officinarum.MethodsKeywords including A. officinarum and its synonyms were searched using electronic databases including ISI web of knowledge, Science direct, Scopus, PubMed, Google scholar and relevant database for Masters and Doctoral theses.ResultsA. officinarum is prepared in Asia, Turkey, Morocco and Iran as a decoction, infusion or juice as a single preparation or in combination with other herbs, food or drinks for the treatment of general health problems including cold, inflammation, digestive disorders, etc. Pharmacological studies revealed the potent in vitro and in vivo bioactivities of various parts of A. officinarum that include anti-inflammatory, cytotoxicity, homeostasis, lipid regulation, antioxidant, antiviral, antimicrobial, antiosteoporosis, etc. Over 90 phytochemical constituents have been identified and isolated from A. officinarum comprising vastly of phenolic compounds especially diarylheptanoids isolated from the rhizome and considered the most active bioactive components.ConclusionIn vitro and in vivo studies have confirmed the potency of A. officinarum. However, further studies are required to establish the mechanisms mediating its bioactivities in relation to the medicinal uses as well as investigating any potential toxicity for future clinical studies.

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Antidiarrheal activity of a novel sulfated polysaccharide from the red seaweed Gracilaria cervicornis

Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Francisco Felipe Bezerra, Glauber Cruz Lima, Nayara Alves de Sousa, Willer Malta de Sousa, Luís Eduardo Costa Castanheira, Douglas Soares da Costa, Francisco Clark Nogueira Barros, Jand Venes Rolim Medeiros, Ana Lúcia Ponte Freitas
Ethnopharmacological relevanceThe use of marine seaweeds as a source of natural compounds with medicinal purposes is increasing in Western countries in the last decades, becoming an important alternative in the traditional medicine of many developing countries, where diarrhea still remains a severe public health problem, with high rates of mortality and morbidity. Sulfated polysaccharides (PLS) extracted from red seaweeds can exhibit therapeutic effects for the treatment of gastrointestinal disorders. Thus, the pharmacological properties of the PLS from Gracilaria cervicornis, an endemic seaweed found in the Brazilian northeast coast, was evaluated as an alternative natural medication for diarrhea.Aim of the studyThis study aimed to evaluate the antidiarrheal activity of sulfated polysaccharides (PLS) extracted from the red seaweed G. cervicornis in Swiss mice pre-treated with castor oil or cholera toxin.Materials and methodsThe seaweed Gracilaria cervicornis was collected at Flecheiras beach (city of Trairí, State of Ceará, Brazil) and the PLS was obtained through enzymatic extraction and administered in mice (25–30 g) before diarrhea induction with castor oil or cholera toxin. For the evaluation of the total number of fecal output and diarrheal feces, the animals were placed in cages lined with adsorbent material. The evaluation of intestinal fluid accumulation (enteropooling) on castor oil-induced diarrhea in mice occurred by dissecting the small intestine and measuring its volume. The determination of Na+/K+-ATPase activity was measured in the small intestine supernatants by colorimetry, using commercial biochemistry kits. The gastrointestinal motility was evaluated utilizing an activated charcoal as a food tracer. The intestinal fluid secretion and chloride ion concentration were evaluated in intestinal closed loops in mice with cholera toxin-induced secretory diarrhea. The binding ability of PLS with GM1 and/or cholera toxin was evaluated by an Enzyme-Linked Immunosorbent Assay (ELISA).ResultsThe G. cervicornis PLS showed antidiarrheal effects in both acute and secretory diarrhea, reducing the total number of fecal output, diarrheic stools, intestinal fluid accumulation, and increasing small intestine Na+/K+-ATPase activity on castor oil-induced diarrhea. However, the PLS did not affect gastrointestinal motility, indicating that this compound has a different action mechanism than loperamide. In secretory diarrhea, the PLS decreased intestinal fluid secretion and small intestine chloride excretion, binding with GM1 and/or cholera toxin and blocking their attachment to the enterocyte cell surface.ConclusionsIn conclusion, PLS has a significant antidiarrheal effect in acute and secretory diarrhea. Further investigation is needed towards its use as a natural medicine to treat diarrhea.

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Comparative pharmacokinetics of six coumarins in normal and breast cancer bone-metastatic mice after oral administration of Wenshen Zhuanggu Formula

Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Weiling Chen, Jiajia Li, Zhenping Sun, Chunyu Wu, Jiao Ma, Jianyi Wang, Sheng Liu, Xianghui Han
Ethnopharmacological relevanceWenshen Zhuanggu Formula (WSZG) is a traditional Chinese medicine (TCM) prescription used in clinics for adjuvant treatment of breast cancer bone metastases in Longhua Hospital in China. WSZG has been reported to decrease the risk of bone metastases and alleviate the severity of bone lesions in a breast cancer xenograft model.Aim of the studyThe present study aimed at investigating the pharmacokinetic behaviors of six coumarins in normal and breast cancer bone-metastatic mice following oral administration of WSZG extract.Materials and methodsA bone-metastatic mouse model was established by intracardiac injection of MDA-MB-231BO breast cancer cells, and WSZG extract (1.60 g/kg) was given orally to the model and normal mice for 4 weeks. Then, the blood pharmacokinetic parameters of six bioactive components from WSZG (psoralen, isopsoralen, bergapten, xanthotoxin, osthole, and imperatorin) were analyzed by liquid chromatography tandem mass spectrometry.ResultsThere were significant differences in pharmacokinetic behaviors between normal and pathological states. Compared with normal mice, the model mice showed significantly increased AUC0–t and AUC0–∞ of the bioactive compounds (P < 0.05) and significantly decreased total blood clearance (CLZ/F) (P < 0.05).ConclusionsThe different pharmacokinetic behaviors might be partly ascribed to intestinal functional disorders and imbalance of gastrointestinal microbiota under the morbid state. The findings provide some valuable information to evaluate the clinical efficacy and safety of this TCM formula.

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Trichophyton erinacei Transmitted to a Pregnant Woman From Her Pet Hedgehogs

This case report describes a pregnant woman who developed tinea manus from Trichophyton erinacei infection transmitted to her from her pet hedgehogs.

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Lentigo Maligna—Challenges, Observations, Imiquimod, Confocal Microscopy, and Personalized Treatment

The word melanoma imparts considerable fear and concern in patients. Fortunately, for patients with the lentigo maligna (LM) subtype of melanoma in situ, there is overall good prognosis. The challenge of LM, however, is that it has the highest rate of local recurrence (approximately 20%) of all melanoma subtypes when treated by standard surgical excision alone, owing to frequent, unpredictable, subclinical extension. To reduce this risk, the use of Mohs surgery or staged excision has consistently demonstrated lower recurrence rates of 0.3% to 2.2% yet requires larger surgical margins for histological clearance than other in situ melanoma subtypes. Moyer et al also demonstrated that with increasing lesion size, both the surgical margin required to clear the lesion and the risk of local recurrence increased, suggesting increased subclinical spread with increasing lesion size. In addition, LM is typically located in the head and neck area, a complex zone with potential cosmetic and functional impairment owing to extensive surgery. Finally, differentiating LM from background atypical melanocytic hyperplasia can be challenging. Thus, treatments directed toward reducing the extent of surgery, minimizing morbidity, and providing a cure would enhance patient outcomes.

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Prevalence of Skin Cancer Examination Among Indoor Tanning Bed Users

This study uses weighted national survey data to examine the prevalence of skin cancer examinations among users of indoor tanning beds.

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Lentigo Maligna Treated With Off-Label Neoadjuvant Imiquimod

This medical record review examines the rate of recurrence of lentigo maligna in patients treated with neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions.

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Adolescents’ Perspectives on Atopic Dermatitis Treatment

This qualitative study examines the beliefs, experiences, and preferences of adolescents with atopic dermatitis toward their treatment via focus groups interviews.

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Multidisciplinary management of oculo-auriculo-vertebral spectrum

Purpose of review Oculo-auriculo-vertebral spectrum (OAVS) is a complex disorder that is represented by wide variations in phenotypic presentation. Recent publications and systematic reviews of the available literature are presented here. Recent findings Treatment strategies vary among craniofacial centers across the country. Advances in presurgical planning, virtual surgical planning, and computer-aided manufacturing have been incorporated in the treatment of patients. The psychosocial effect of OAVS with longitudinal follow-up is now being studied. Summary Optimal evaluation and management of the OAVS patient requires an awareness of the phenotypic and genetic differences and involves a multidisciplinary team in order to effectively and appropriately diagnose and treat such patients. Correspondence to Jamie Funamura, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, University of California Davis, 2521 Stockton Blvd, Ste 7200, Sacramento, CA 95817, USA. E-mail: jlfunamura@ucdavis.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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