Scholar : Undersea "Hyperbaric Medicine" - νέα αποτελέσματα

[PDF] Chronic Decompression Illness Cognitive Dysfunction Improved with Hyperbaric Oxygen: A Case Report

EG Wolf, KR Bradley, MF Richards, DP Beckstrand - 2018

… Distribution is unlimited. 00S aaGGLLGYYGLGGGLLG GGGLS Undersea and Hyperbaric
Medicine 14. AE3STRACT 15. SUEJECT TERRIS 16. SECURITY CLASSIFICATION OF: 00S
LLLLLL GGGGGGG GGS a. REPORT | b. AESTRACT CS GGL GGLL ABSTRACT 18 …

[PDF] The Analysis of Drive Systems in Unmanned Underwater Vehicles Towards Identifying the Method of Drive Transmission–Part 2

B Jakus, A Olejnik - Polish Hyperbaric Research, 2017

Page 1. POLISH HYPERBARIC RESEARCH 3(60)2017 Journal of Polish Hyperbaric
Medicine and Technology Society THE ANALYSIS OF DRIVE SYSTEMS IN
UNMANNED UNDERWATER VEHICLES TOWARDS IDENTIFYING …

[PDF] The Analysis of Drive Systems in Unmanned Underwater Vehicles Towards Identifying the Method of Drive Transmission

B Jakus, A Olejnik - Polish Hyperbaric Research, 2017

… 30 PM Page 2. 2017 Vol. 60 Issue 3 Journal of Polish Hyperbaric Medicine and
Technology Society INTRODUCTION Unmanned underwater vehicles have been
used for years in the exploration of bodies of water. The scope …

[PDF] Hyperbaric Oxygen Therapy (HBOT) as a Therapeutic Option for Patients with Atopic Dermatitis (AD)–Own Experiences and Literature Review

R Olszański, M Konarski, P Siermontowski - Polish Hyperbaric Research, 2017

… Department, Gdynia, Military Institute of Medicine in Warsaw, Poland 2) Department of Underwater
Works Technology … Mathieu D, Marroni A, Kot J (2017) Tenth European Consensus Conference
on Hyperbaric Medicine: recommendations for … Undersea Hyperb Med 22: 395-399 …

[HTML] A Software Tool for the Annotation of Embolic Events in Echo Doppler Audio Signals

P Pierleoni, L Maurizi, L Palma, A Belli, S Valenti… - Biomedical Informatics …, 2017

The use of precordial Doppler monitoring to prevent decompression sickness (DS) is well known
by the scientific community as an important instrument for early d...

[PDF] The Effect of Breathing Mixtures on Physical Capacity of Rats in Hyperbaric Conditions

T Doboszyński, B Łokucijewski, P Siermontowski… - Polish Hyperbaric Research, 2017

… Journal of Polish Hyperbaric Medicine and Technology Society INTRODUCTION A high interest
in long-term underwater stays, whether for commercial, recreational or sports-related purposes,
raises the need for experimental research aimed at determining the factors which …

[PDF] Multi-Agent Responsibility for a Tragic Accident in Water

W Wiesner - Polish Hyperbaric Research, 2017

… PM Page 4. 2017 Vol. 60 Issue 3 Journal of Polish Hyperbaric Medicine and Technology
Society Tab. 1 Selected events … much more. Underwater activities (eg cave diving, wreck
diving, etc.) are certainly among them as well. Proposing …

[PDF] Preliminary results of a multivariate analysis of 466 cases following a prospective study

J Desola, J Sala, J Bohe, A Garcia, M Gomez, S Graus…

… Kanjuk and V. Gajić I 194 Page 8. DIVING AND HYPERBARIC MEDICINE Proceedings of the
XXIII Annual Scientific Meeting of the European Underwater and Baromedical Society ", EURS
Q7 Bled, Slovenia Editors: Igor B. Mekjavić Michael J. Tipton Ola Eiken Page 9 …

---

Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

Ακύρωση ειδοποίησης
Δημιουργία λίστας των ειδοποιήσεών μου

Molecular mechanism of LPS-induced TNF-α biosynthesis in polarized human macrophages

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Erik Schilling, Ronald Weiss, Anja Grahnert, Michael Bitar, Ulrich Sack, Sunna Hauschildt
In response to environmental stimuli such as granulocyte-macrophage or macrophage colony stimulating factor (GM-CSF/M-CSF), macrophages (MΦ) can acquire distinct functional phenotypes that control inflammatory processes on the one hand and contribute to a broad spectrum of pathologies on the other. Potential intervention strategies will require an understanding of the signalling processes that are associated with macrophage polarization.In the present study, we show that M-MΦ produce more IFN-β and IL-10 and a lot less TNF-α than do GM-MΦ in response to LPS. To define the molecular mechanisms that underlie the biosynthesis of TNF-α we carried out a detailed investigation of the LPS-induced activation of the canonical and non-canonical myeloid differentiation primary response 88 (MyD88)-dependent signal transduction pathways as well as the TIR-domain-containing adapter-inducing interferon-β (TRIF)-dependent pathway. Our results show that all three pathways are activated in both cell types and that the activation is more pronounced in M-MΦ. While IL-10 was found to interfere with TNF-α production in M-MΦ, we exclude a decisive role for IFN-β in this respect. Furthermore, we demonstrate that TNF-α mRNA is markedly destabilized in M-MΦ and that expression of the mRNA destabilizing protein tristetraprolin is greatly enhanced in these cells.Collectively, our study suggests that differential effects of LPS on TNF-α mRNA turnover and on signal transduction pathways influence the amount of TNF-α finally produced by GM-MΦ and M-MΦ.



http://ift.tt/2kp00d6

Phospholipase A1-based cross-reactivity among venoms of clinically relevant Hymenoptera from Neotropical and temperate regions

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Amilcar Perez-Riverol, Luís Gustavo Romani Fernandes, Alexis Musacchio Lasa, José Roberto Aparecido dos Santos-Pinto, Débora Moitinho Abram, Gabriel Hideki Izuka Moraes, Frederic Jabs, Michaela Miehe, Henning Seismman, Mario Sergio Palma, Ricardo de Lima Zollner, Edzard Spillner, Márcia Regina Brochetto-Braga
Molecular cross-reactivity caused by allergen homology or cross-reactive carbohydrate determinants (CCDs) is a major challenge for diagnosis and immunotherapy of insect venom allergy. Venom phospholipases A1 (PLA1s) are classical, mostly non-glycosylated wasp and ant allergens that provide diagnostic benefit for differentiation of genuine sensitizations from cross-reactivity. As CCD-free molecules, venom PLA1s are not causative for CCD-based cross-reactivity. Little is known however about the protein-based cross-reactivity of PLA1 within vespid species. Here, we address PLA1-based cross-reactivity among ten clinically relevant Hymenoptera venoms from Neotropical and temperate regions including Polybia paulista (paulistinha) venom and Vespula vulgaris (yellow jacket) venom. In order to evaluate cross-reactivity, sera of mice sensitized with recombinant PLA1 (rPoly p 1) from P. paulista wasp venom were used. Pronounced IgE and IgG based cross-reactivity was detected for wasp venoms regardless the geographical region of origin. The cross-reactivity correlated well with the identity of the primary sequence and 3-D models of PLA1 proteins. In contrast, these mice sera showed no reaction with honeybee (HBV) and fire ant venom. Furthermore, sera from patients monosensitized to HBV and fire ants did not recognize the rPoly p 1 in immunoblotting. Our findings reveal the presence of conserved epitopes in the PLA1s from several clinically relevant wasps as major cause of PLA1-based in vitro cross-reactivity. These findings emphasize the limitations but also the potential of PLA1-based HVA diagnostics.

Graphical abstract

http://ift.tt/2jSCfKZ

Asparaginase inhibits the lectin pathway of complement activation

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): M.P. Keizer, C. Aarts, A.M. Kamp, H.N. Caron, M.D. van de Wetering, D. Wouters, T.W. Kuijpers
Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated. A prominent defect observed in C2012 was the inhibition of the lectin pathway (LP) of complement activation during the treatment of acute lymphoblastic leukemia (ALL), which we could directly associate to the use of asparaginase (ASNase). Ex-vivo experiments confirmed a direct dose-dependent inhibitory effect of ASNase on the LP functionality.



http://ift.tt/2jRYPDz

Scholar : ΟΓΚΟΛΟΓΙΑ - νέα αποτελέσματα

[PDF] Καρκίνος του παγκρέατος. Ο ρόλος του νοσηλευτή

Α ΓΕΩΡΓΙΟΥ - 2017

Page 1. ΤΕΧΝΟΛΟΓΙΚΟ ΕΚΠΑΙΔΕΥΤΙΚΟ ΙΔΡΥΜΑ ΔΥΤΙΚΗΣ ΕΛΛΑΔΑΣ ΣΧΟΛΗ ΕΠΑΓΓΕΛΜΑΤΩΝ
ΥΓΕΙΑΣ ΚΑΙ ΠΡΟΝΟΙΑΣ ΤΜΗΜΑ ΝΟΣΗΛΕΥΤΙΚΗΣ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ ΚΑΡΚΙΝΟΣ ΤΟΥ
ΠΑΓΚΡΕΑΤΟΣ . Ο ΡΟΛΟΣ ΤΟΥ ΝΟΣΗΛΕΥΤΗ ΣΠΟΥΔΑΣΤΡΙΑ: Γεωργίου Αγγελική …

---

Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

Ακύρωση ειδοποίησης
Δημιουργία λίστας των ειδοποιήσεών μου

DNA/RNA hybrid substrates modulate the catalytic activity of purified AID

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Hala S. Abdouni, Justin J. King, Atefeh Ghorbani, Heather Fifield, Lesley Berghuis, Mani Larijani
Activation–induced cytidine deaminase (AID) converts cytidine to uridine at Immunoglobulin (Ig) loci, initiating somatic hypermutation and class switching of antibodies. In vitro, AID acts on single stranded DNA (ssDNA), but neither double-stranded DNA (dsDNA) oligonucleotides nor RNA, and it is believed that transcription is the in vivo generator of ssDNA targeted by AID. It is also known that the Ig loci, particularly the switch (S) regions targeted by AID are rich in transcription-generated DNA/RNA hybrids. Here, we examined the binding and catalytic behavior of purified AID on DNA/RNA hybrid substrates bearing either random sequences or GC-rich sequences simulating Ig S regions. If substrates were made up of a random sequence, AID preferred substrates composed entirely of DNA over DNA/RNA hybrids. In contrast, if substrates were composed of S region sequences, AID preferred to mutate DNA/RNA hybrids over substrates composed entirely of DNA. Accordingly, AID exhibited a significantly higher affinity for binding DNA/RNA hybrid substrates composed specifically of S region sequences, than any other substrates composed of DNA. Thus, in the absence of any other cellular processes or factors, AID itself favors binding and mutating DNA/RNA hybrids composed of S region sequences. AID:DNA/RNA complex formation and supporting mutational analyses suggest that recognition of DNA/RNA hybrids is an inherent structural property of AID.



http://ift.tt/2koAKUi

Scholar : ΥΔΡΩΠΑΣ - νέα αποτελέσματα

[PDF] Διατροφικά προβλήματα των ασθενών με Β-Θαλασσαιμία: Διερεύνηση διατροφικών γνώσεων σε δείγμα ασθενών.

Θ Βασιλαντωνάκη, T Vasilantonaki - 2017

Page 1. Πτυχιακή Εργασία «Διατροφικά προβλήματα των ασθενών με Β-Θαλασσαιμία: Διερεύνηση
διατροφικών γνώσεων σε δείγμα ασθενών» «Βασιλαντωνάκη Θεοπούλα» Α.Μ.: 2048 Επιβλέπουσα
καθηγήτρια: «Ειρήνη Σφακιανάκη» ΣΗΤΕΙΑ, Νοέμβριος 2017 Page 2. THESIS …

---

Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

Ακύρωση ειδοποίησης
Δημιουργία λίστας των ειδοποιήσεών μου

Natural killer cells and anti-tumor immunity

Publication date: Available online 9 December 2017
Source:Molecular Immunology
Author(s): Sandra E. Nicholson, Narelle Keating, Gabrielle T. Belz
Immune checkpoint inhibitors harness the power of the immune system to fight cancer. The clinical success achieved with antibodies against the inhibitory T cell receptors PD-1 and CTLA4 has focused attention on the possibility of manipulating other immune cells, in particular those involved in innate immunity. Here we review the role of innate lymphoid cells (ILCs) and their contribution to tumor immunity. As the prototypical ILC, the natural killer (NK) cell has an intrinsic ability to detect and kill cancer cells. NK cells are dependent on the cytokine interleukin (IL)-15 for their development and effector activity. We discuss the role of the Suppressor of cytokine (SOCS) proteins in negatively regulating IL-15 and NK cell responses and the potential for targeting these small intracellular regulators as new immune checkpoints.



http://ift.tt/2jRYIb7

Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Yong Han, Jie Ma, Junping Wang, Liping Wang
Atherosclerosis (AS) is the main cause of cardiovascular diseases (CADs). Lipid accumulation and inflammatory response in macrophages are two key factors in the pathogenesis of AS. In this study, we aimed to explore the regulating role of long non-coding RNA (LncRNA)-H19 in oxygenized low density lipoprotein (ox-LDL)-treated Raw264.7 cells. Compared with the healthy control, a relatively higher level of H19 was detected in the blood samples from AS patients. Obviously up-regulated expression of TG (triglycerides)/TC (total cholesterol)/LDL-C (low density lipoprotein-cholesterol) and down-regulated level of HDL-C (high density lipoprotein-cholesterol) were detected in ox-LDL-treated Raw264.7 cells. Besides that, increased expression of H19 was detected in ox-LDL-treated Raw264.7 cells. To examine the function of H19, gene knockdown was performed using short hairpin RNAs (shRNAs). The expression of TG, TC, LDL-C and HDL-C was detected by enzyme linked immunosorbent assay (Elisa) and the expression of lipolytic genes/lipogenic genes (PPARα, CPT-1/REBP-1c, ACS) was examined through western blot. In combination with the result of oil red O staining, we concluded that H19 shRNA effectively decreased lipid accumulation in ox-LDL-treated Raw264.7 cells. Besides that, H19 shRNA decreased the level of pro-inflammatory factors (TNF-α, IL-1β)/CD68+ cells and increased the level of anti-inflammatory factors (IL-4, IL-10)/CD163+ cells compared with the control group. Combined the bioinformatics analyses/luciferase assay with the promoting effect of H19 shRNA on the expression of miR-130b, we speculated that miR-130b was a target of H19 in ox-LDL-treated Raw264.7 cells. Moreover, the adding of LncRNA H19 abolished the facilitating effect of miR-130b inhibitor on adipogenesis and inflammation response by up-regulating the expression of miR-130b. Taken together, our research indicated a H19-miR130b pathway in regulating lipid metabolism and inflammation response in ox-LDL-treated Raw264.7 cells, providing new targets for AS treatment.



http://ift.tt/2koDDEP

The 20S immunoproteasome and constitutive proteasome bind with the same affinity to PA28αβ and equally degrade FAT10

Publication date: Available online 6 December 2017
Source:Molecular Immunology
Author(s): Gunter Schmidtke, Richard Schregle, Gerardo Alvarez, Eva M. Huber, Marcus Groettrup
The 20S immunoproteasome (IP) is an interferon(IFN)-γ − and tumor necrosis factor (TNF) −inducible variant of the 20S constitutive proteasome (CP) in which all its peptidolytically active subunits β1, β2, and β5 are replaced by their cytokine inducible homologues β1i (LMP2), β2i (MECL-1), and β5i (LMP7). These subunit replacements alter the cleavage specificity of the proteasome and the spectrum of proteasome-generated peptide ligands of MHC class I molecules. In addition to antigen processing, the IP has recently been shown to serve unique functions in the generation of pro-inflammatory T helper cell subtypes and cytokines as well as in the pathogenesis of autoimmune diseases, but the mechanistic involvement of the IP in these processes has remained elusive. In this study we investigated whether the IP differs from the CP in the interaction with two IFN-γ/TNF inducible factors: the 11S proteasome regulator PA28αβ and the ubiquitin-like modifier FAT10 (ubiquitin D). Using thermophoresis, we determined the affinity of PA28αβ for the CP and IP to be 12.2nM +/− 2.8nM and 15.3nM +/− 2.7nM, respectively, which is virtually identical. Also the activation of the peptidolytic activities of the IP and CP by PA28αβ did not differ. For FAT10 we determined the degradation kinetics in cycloheximide chase experiments in cells expressing almost exclusively IP or CP as well as in IFN-γ stimulated and unstimulated cells and found no differences between the degradation rates. Taken together, we conclude that neither differences in the binding strength to, nor activation by PA28αβ, nor a difference in the rate of FAT10-mediated degradation can account for distinct functional capabilities of the IP as compared to the CP.

Graphical abstract

http://ift.tt/2jQ49HA

Scholar : Canadian Art Therapy Association Journal, Volume 30, Issue 2, July 3, 2017 is now available online on Taylor & Francis Online

@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }

The online platform for Taylor & Francis Online content Canadian Art Therapy Association Journal, Volume 30, Issue 2, July 3, 2017 is now available online on Taylor & Francis Online. Art Therapy and Visual Culture This new issue contains the following articles: Editorial 30th Anniversary, Canadian Art Therapy Association Journal. Visual Culture: Art Therapy Out of Bounds (30e anniversaire, Revue de l'Association canadienne d'art-thérapie. Culture visuelle : l'art-thérapie hors limites) Pamela Whitaker PhD, MA, BA, DVATI Pages: 53-55 | DOI: 10.1080/08322473.2017.1387472 Articles Art Therapist-Facilitated Open Studio Versus Coloring: Differences in Outcomes of Affect, Stress, Creative Agency, and Self-Efficacy (Studio ouvert animé par un art-thérapeute versus coloriage : différences de résultats sur l'affect, le stress, l'agentivité créatrice et l'efficacité personnelle) | Girija Kaimal EdD, MA, Janell L. Mensinger PhD, Jessica M. Drass MA, ATR-BC & Rebekka M. Dieterich-Hartwell MA, BC-DMT Pages: 56-68 | DOI: 10.1080/08322473.2017.1375827 Exploring the Museum's Images – Exploring My Image (Exploration des images du musée, exploration de mon image) Aphrodite Pantagoutsou, Elisabeth Ioannides & Grigoris Vaslamatzis MD Pages: 69-77 | DOI: 10.1080/08322473.2017.1375769 Art Therapy in Practice Creating Community and Shattering Stigma: Collaborative Arts Interventions for the Forensic Population (Création de communauté et réduction de la stigmatisation : interventions artistiques collaboratives avec des personnes bénéficiant de services de psychiatrie légale) Jaimie Peterson MAAT, ATR & Alison Etter MT-BC Pages: 78-87 | DOI: 10.1080/08322473.2017.1381511 Standing Tall: Students Showcase Resiliency Through Body Tracings (Standing Tall: la résilience en vitrine dans les tracés corporels d'étudiants) Marygrace Berberian LCAT, ATR-BC, LCSW Pages: 88-93 | DOI: 10.1080/08322473.2017.1375734 Soundings Public Practice Art Therapy: Enabling Spaces Across North America (La pratique publique de l'art-thérapie : des espaces habilitants partout en Amérique du Nord) Janis Timm-Bottos PhD, ATR-BC Pages: 94-99 | DOI: 10.1080/08322473.2017.1385215 Book Reviews The Art of Play: Ignite Your Imagination to Unlock Insight, Healing, and Joy (L'art du jeu : stimuler votre imagination pour ouvrir sur l'introspection, la guérison et la joie), by Joan Stanford Lucia Capacchione PhD, ATR, REAT Pages: 100-101 | DOI: 10.1080/08322473.2017.1378517 When Art Therapy Meets Sex Therapy: Creative Explorations of Sex, Gender and Relationships (Quand l'art-thérapie rencontre la thérapie sexuelle : explorations créatives du sexe, du genre et des relations), by Einat S. Metzl Santoshi (Tammy) Robertson Davis BCR Pages: 101-102 | DOI: 10.1080/08322473.2017.1378515 Introduction to Art Therapy: Faith in the Product, 3rd Edition (Introduction à l'art-thérapie : la foi dans le produit, 3e édition) by Bruce L. Moon Naomi Kates DTATI Pages: 102-103 | DOI: 10.1080/08322473.2017.1378495 Miscellaneous Editorial Board EOV Pages: ebi-ebi | DOI: 10.1080/08322473.2017.1400345 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Linking T cell epitopes to a common linear B cell epitope: A targeting and adjuvant strategy to improve T cell responses

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Sara M. Mangsbo, Erika A.K. Fletcher, Wendy W.C. van Maren, Anke Redeker, Robert A. Cordfunke, Inken Dillmann, Jasper Dinkelaar, Kahina Ouchaou, Jeroen D.C. Codee, Gijs A. van der Marel, Peter Hoogerhout, Cornelis J.M. Melief, Ferry Ossendorp, Jan W. Drijfhout
Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd. This protein conjugate enhanced OVA-specific CD8+ T cell responses when administrated to seropositive mice. Since TTd is poorly defined, we next investigated whether a synthetic peptide–peptide conjugate, with a chemically defined linear B cell epitope of tetanus toxin (TTx) origin, could improve cellular immune responses. Herein we identify one linear B cell epitope, here after named MTTE thru a screening of overlapping peptides from the alpha and beta region of TTx, and by assessment of the binding of pooled IgG, or individual human IgG from high-titer TTd vaccinated donors, to these peptides. Subsequently, we developed a chemical protocol to synthesize defined conjugates containing multiple copies of MTTE covalently attached to one or more T cell epitopes of choice. To demonstrate the potential of the above approach we showed that immune complexes of anti-MTTE antibodies with MTTE-containing conjugates are able to induce DC and T cell activation using model antigens.



http://ift.tt/2jRYAZb

Rational selection of immunodominant and preserved epitope Sm043300e from Schistosoma mansoni and design of a chimeric molecule for biotechnological purposes

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Cláudia de Souza, Marcelo Donizete Lopes, Flávio Martins De Oliveira, Maria Juliana Ferreira Passos, Laís Cunha Grossi Ferreira, Bruna Franciele Faria, José Augusto Ferreira Perez Villar, Moacyr Comar Junior, Alex Guterres Taranto, Luciana Lara dos Santos, Cristina Toscano Fonseca, Débora de Oliveira Lopes
Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis. Furthermore, epitope recognition was evaluated using sera of individuals infected with S. mansoni. The epitope that stood out in both in silico and in vitro assays was used to compose a rational chimeric molecule to improve immune response activation. Out of 2185 transmembrane proteins, four epitopes with high binding affinities for human and mouse MHCII molecules were selected through computational screening. These epitopes were synthesized to evaluate their ability to induce TCD4+ lymphocyte proliferation in mice. Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes were submitted to enzyme-linked immunosorbent assay to evaluate their recognition by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was significantly recognized in most sera samples. Epitope Sm043300 also showed good affinity for human MHCII molecules in molecular docking, and its sequence is curiously highly conserved in four S. mansoni proteins, all of which are described as G-protein-coupled receptors. In addition, we have demonstrated the feasibility of incorporating this epitope, which showed low similarity to human sequences, into a chimeric molecule. The stability of the molecule was evaluated by molecular modeling aimed at future molecule production for use in diagnosis and vaccination trials.



http://ift.tt/2kp9nJL

Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Shixuan Wang, Yue Guan, Yunlong Wang, Huiyuan Li, Donglei Zhang, Mankai Ju, Yating Hao, Xuewen Song, Boyang Sun, Xueqing Dou, Renchi Yang
Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. This pathway is important for activation, growth, and proliferation. Although enhanced B cell receptor (BCR) signaling contributes to increased B cell activity in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we analyzed B cells of ITP patients using flow cytometry and found that all B cell subsets, excluding memory B cells, showed lower PTEN expression than cells from healthy controls (HCs). PTEN expression was also positively-correlated with blood platelet count, although levels were lower in patients who were platelet autoantibody-positive compared with those who were negative. We next evaluated the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that they were potent inducers of PTEN expression in normal B cells. Induction of PTEN expression was lower in B cells of ITP patients. We also found that IL-21 increased the proportion of plasma cells in peripheral blood mononuclear cells (PBMCs) of ITP patients, independent of BCR signaling. This effect was reproducible using PTEN inhibitors with cells from HCs. In summary, defective PTEN expression, regulation, and function all contribute to the B cell hyper-responsiveness that associates with ITP.



http://ift.tt/2jRYuRj

Discovery of microRNAs associated with the antiviral immune response of Atlantic cod macrophages

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Khalil Eslamloo, Sabrina M. Inkpen, Matthew L. Rise, Rune Andreassen
MicroRNAs (miRNAs) are known to play important immunoregulatory roles in teleosts, although miRNAs involved in the antiviral immune response of Atlantic cod (Gadus morhua) were previously uncharacterised. Using deep sequencing and qPCR, the present study was conducted to identify miRNAs responsive to the viral mimic, polyriboinosinic polyribocytidylic acid (pIC) in Atlantic cod macrophages. Macrophage samples isolated from Atlantic cod (n=3) and treated with pIC or phosphate buffered saline (PBS control) for 24 and 72h were used for miRNA profiling. Following deep sequencing, DESeq2 analyses identified four (miR-731-3p, miR-125b-3-3p, miR-150-3p and miR-462-3p) and two (miR-2188-3p and miR-462-3p) significantly differentially expressed miRNAs at 24 and 72h post-stimulation (HPS), respectively. Sequencing-identified miRNAs were subjected to qPCR validation using a larger number of biological replicates (n=6) exposed to pIC or PBS over time (i.e. 12, 24, 48 and 72 HPS). As in sequencing, miR-731-3p, miR-462-3p and miR-2188-3p showed significant up-regulation by pIC. The sequencing results were not qPCR-validated for miR-125b-3-3p and miR-150-3p as up- and down-regulated miRNAs at 24 HPS, respectively; however, qPCR results showed significant up-regulation in response to pIC stimulation at later time points (i.e. 48 and/or 72 HPS). We also used qPCR to assess the expression of other miRNAs that were previously shown as immune responsive in other vertebrates. qPCR results at 48 and/or 72 HPS revealed that miR-128-3-5p, miR-214-1-5p and miR-451-3p were induced by pIC, whereas miR-30b-3p and miR-199-1-3p expression were repressed in response to pIC. The present study identified ten pIC-stimulated miRNAs, suggesting them as important in antiviral immune responses of Atlantic cod macrophages. Some pIC-responsive miRNAs identified in this study were predicted to target putative immune-related genes of Atlantic cod (e.g. miR-30b-3p targeting herc4), although the regulatory functions of these miRNAs need to be validated by future studies.



http://ift.tt/2kp9ipr

IL-17 is a protection effector against the adherent-invasive Escherichia coli in murine colitis

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Hai-jia Zhang, Bin Xu, Hu Wang, Bing Xu, Guo-dong Wang, Ming-zuo Jiang, Chao Lei, Mei-ling Ding, Peng-fei Yu, Yong-zhan Nie, Kai-chun Wu, Su-mei Sha, Meng-bin Li
Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion.



http://ift.tt/2jRYqkx

Spatiotemporal Bayesian networks for malaria prediction

Publication date: Available online 11 December 2017
Source:Artificial Intelligence in Medicine
Author(s): Peter Haddawy, A.H.M. Imrul Hasan, Rangwan Kasantikul, Saranath Lawpoolsri, Patiwat Sa-angchai, Jaranit Kaewkungwal, Pratap Singhasivanon
Targeted intervention and resource allocation are essential for effective malaria control, particularly in remote areas, with predictive models providing important information for decision making. While a diversity of modeling technique have been used to create predictive models of malaria, no work has made use of Bayesian networks. Bayes nets are attractive due to their ability to represent uncertainty, model time lagged and nonlinear relations, and provide explanations. This paper explores the use of Bayesian networks to model malaria, demonstrating the approach by creating village level models with weekly temporal resolution for Tha Song Yang district in northern Thailand. The networks are learned using data on cases and environmental covariates. Three types of networks are explored: networks for numeric prediction, networks for outbreak prediction, and networks that incorporate spatial autocorrelation. Evaluation of the numeric prediction network shows that the Bayes net has prediction accuracy in terms of mean absolute error of about 1.4 cases for 1 week prediction and 1.7 cases for 6 week prediction. The network for outbreak prediction has an ROC AUC above 0.9 for all prediction horizons. Comparison of prediction accuracy of both Bayes nets against several traditional modeling approaches shows the Bayes nets to outperform the other models for longer time horizon prediction of high incidence transmission. To model spread of malaria over space, we elaborate the models with links between the village networks. This results in some very large models which would be far too laborious to build by hand. So we represent the models as collections of probability logic rules and automatically generate the networks. Evaluation of the models shows that the autocorrelation links significantly improve prediction accuracy for some villages in regions of high incidence. We conclude that spatiotemporal Bayesian networks are a highly promising modeling alternative for prediction of malaria and other vector-borne diseases.



http://ift.tt/2yh9MD0

A novel method for predicting kidney stone type using ensemble learning

Publication date: Available online 11 December 2017
Source:Artificial Intelligence in Medicine
Author(s): Yassaman Kazemi, Seyed Abolghasem Mirroshandel
The high morbidity rate associated with kidney stone disease, which is a silent killer, is one of the main concerns in healthcare systems all over the world. Advanced data mining techniques such as classification can help in the early prediction of this disease and reduce its incidence and associated costs. The objective of the present study is to derive a model for the early detection of the type of kidney stone and the most influential parameters with the aim of providing a decision-support system. Information was collected from 936 patients with nephrolithiasis at the kidney center of the Razi Hospital in Rasht from 2012 through 2016. The prepared dataset included 42 features. Data pre-processing was the first step toward extracting the relevant features. The collected data was analyzed with Weka software, and various data mining models were used to prepare a predictive model. Various data mining algorithms such as the Bayesian model, different types of Decision Trees, Artificial Neural Networks, and Rule-based classifiers were used in these models. We also proposed four models based on ensemble learning to improve the accuracy of each learning algorithm. In addition, a novel technique for combining individual classifiers in ensemble learning was proposed. In this technique, for each individual classifier, a weight is assigned based on our proposed genetic algorithm based method. The generated knowledge was evaluated using a 10-fold cross-validation technique based on standard measures. However, the assessment of each feature for building a predictive model was another significant challenge. The predictive strength of each feature for creating a reproducible outcome was also investigated. Regarding the applied models, parameters such as sex, acid uric condition, calcium level, hypertension, diabetes, nausea and vomiting, flank pain, and urinary tract infection (UTI) were the most vital parameters for predicting the chance of nephrolithiasis. The final ensemble-based model (with an accuracy of 97.1%) was a robust one and could be safely applied to future studies to predict the chances of developing nephrolithiasis. This model provides a novel way to study stone disease by deciphering the complex interaction among different biological variables, thus helping in an early identification and reduction in diagnosis time.



http://ift.tt/2AwAYUd

Scholar : Critique: Studies in Contemporary Fiction, Volume 59, Issue 1, 2018 is now available online on Taylor & Francis Online

@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }

The online platform for Taylor & Francis Online content Critique: Studies in Contemporary Fiction, Volume 59, Issue 1, 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles Updike's Creative So(u)rcery in Gertrude and Claudius George L. Geckle Pages: 1-14 | DOI: 10.1080/00111619.2017.1361268 John Updike and David Foster Wallace: Of Binaries, Sports Writing, and Transcendence James Schiff Pages: 15-26 | DOI: 10.1080/00111619.2017.1378611 Staging the Uneven World of Cybercapitalism on 47th Street in Don DeLillo's Cosmopolis Jung-Suk Hwang Pages: 27-40 | DOI: 10.1080/00111619.2017.1360832 "Pressing the Wrong Button": Pynchon's Postmodernism and the Threat of Nuclear War in The Crying of Lot 49 Jonathan Najarian Pages: 41-56 | DOI: 10.1080/00111619.2017.1357530 Toward a Poetics of Posthumanist Narrative Using Ruth Ozeki's A Tale for the Time Being Sue Lovell Pages: 57-74 | DOI: 10.1080/00111619.2017.1360834 "Extravagant Secular Swarming": Space and Subjectivity in China Mieville's Perdido Street Station Robert Wood Pages: 75-89 | DOI: 10.1080/00111619.2017.1357529 Writing as Echo-Making in and after the Anthropocene Christopher D. Morris Pages: 90-102 | DOI: 10.1080/00111619.2017.1357531 Writing the Rape in Post-Conflict Societies of the 1990s: John M. Coetzee and Slavenka Drakulić Neval Berber Pages: 103-114 | DOI: 10.1080/00111619.2017.1354811 "A Love Story Pure and Simple": Harper Lee and Atticus Finch Hannah Epperson Pages: 115-125 | DOI: 10.1080/00111619.2017.1354810 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Surgical Management of Deep Brain Stimulator Scalp Erosion without Hardware Removal

Background: Scalp erosion in patients with deep brain stimulation (DBS) hardware is an uncommon complication that lacks a clearly defined management strategy. Previous studies have described various therapies including conservative treatment with antibiotics and surgical debridement with or without hardware removal. Objectives: The aim of this study was to review the efficacy of a hardware-sparing management strategy for the treatment of scalp erosion. Methods: Five patients with previous DBS implantation presented with scalp erosion and visible hardware exposure at the calvarial burr hole site, and underwent tension-free, vascularized, rotational scalp flap, with preservation of the leads under the pericranium. Two of the procedures were performed after an unsuccessful attempt at primary closure and 3 as a primary procedure. Each patient was followed clinically for at least 14 months postoperatively to evaluate for wound-healing and adverse effects. Results: The median duration from initial DBS hardware implantation to erosion and revision surgery was 12 months (range 1.5-62 months). Three patients were documented to have positive intraoperative cultures in spite of the absence of purulence. At the last follow-up, all patients were noted to have complete wound-healing and no evidence of infection or erosion. Conclusions: DBS scalp erosion can be managed by rotational scalp flap without hardware removal, even in cases where infection is identified.
Stereotact Funct Neurosurg 2017;95:385-391

http://ift.tt/2Bb70Ej

The science behind skin care: Cleansers

Summary

Two of the most important skin care categories with profound dermatologic implications are cleansers and moisturizers. Cleansers are composed of alkaline soaps or the less barrier-damaging synthetic detergents, known as syndets. The lower skin irritation and dryness found with syndets are related to their reduced tendency to cause protein denaturation due to the charge density of protein-bound micelle-like surfactant aggregates. Many cleansing formulations are available for purchase to meet hygiene needs varying by sex, age, ethnicity, occupation, environment, personal preferences, and the presence or absence of skin disease. This discussion covers the science of skin cleansing.

http://ift.tt/2C5gsHv

Does misuse lead to a disorder? The misuse of prescription tranquilizer and sedative medications and subsequent substance use disorders in a U.S. longitudinal sample

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): C.J. Boyd, B. West, S.E. McCabe
ObjectivesWe used two waves of National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) data and examined whether the misuse of prescription tranquilizers or sedatives at Wave 1 was associated with either continued misuse, tranquilizer/sedative use disorder, or other substance use disorder (SUD) at Wave 2.MethodsProspective data were analyzed from structured diagnostic interviews using the Alcohol Use disorders and Associated Disabilities Interview Schedule: DSM-IV Version (AUDADIS-DSM-IV). A nationally representative sample of 34,653 of U.S. adults, 18years or older at Wave 1 (2001−2002), were re-interviewed at Wave 2 (2004–2005). After applying the survey weights, the sample represented a population that was 52% female, 71% White, 12% Hispanic, 11% African American, 4% Asian and 2% Native American or other.ResultsAn estimated 79% of adults who engaged in tranquilizer or sedative misuse at Wave 1 had stopped using these drugs at Wave 2. Only a small percentage (4.3%) of misusers at Wave 1 had a tranquilizer or sedative use disorder at Wave 2. However, 45% (45.0%) of misusers at Wave 1 had at least one other SUD at Wave 2. Among those in remission from a sedative or tranquilizer use disorder at Wave 1, 4.8% had a tranquilizer or sedative use disorder while 34.7% had at least one other SUD at Wave 2.ConclusionsMost adults who engaged in the misuse of prescription tranquilizers or sedatives ceased using within 3years; however, their prior misuse was associated with higher prevalence of having a SUD three years later.



http://ift.tt/2jxkofK

The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Mieke H.J. Schulte, Reinout W. Wiers, Wouter J. Boendermaker, Anna E. Goudriaan, Wim van den Brink, Denise S. van Deursen, Malte Friese, Emily Brede, Andrew J. Waters
IntroductionEffective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data.MethodsTwenty-four of 38 cocaine-using men completed a 25-day intervention with 2400mg/day NAC or placebo and WM-training as well as two lab-visits assessing cocaine use, craving and inhibition (Stop Signal task). Additionally, cocaine use, craving and cognition (Stroop task) were assessed using EMA during treatment, with 26 participants completing 819 assessments.ResultsCocaine problems according to the Drug Use Disorder Identification Test (DUDIT) decreased more after NAC than after placebo, and the proportion of cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects were found on craving. For cocaine use and craving, results from the lab data were generally similar to EMA results. NAC also showed some effects on cognitive control: improved inhibition assessed with the Stop Signal task in the lab, and decreased classic Stroop performance during EMA. There were no significant effects of number of completed WM-training sessions.ConclusionsOverall this study revealed mixed findings regarding the treatment of cocaine use disorders with NAC and WM-training. The effect of NAC on inhibition should be further investigated.



http://ift.tt/2BglS50

Scholar : These new articles for Critical Inquiry in Language Studies are available online

The online platform for Taylor & Francis Online content New for Critical Inquiry in Language Studies and online now on Taylor & Francis Online: Original Articles Being and becoming an ESOL teacher through coursework and internship: Three teacher candidates' identity negotiation Bedrettin Yazan Pages: 1-23 | DOI: 10.1080/15427587.2017.1408014 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Acta Agriculturae Scandinavica, Section B — Soil & Plant Science, Volume 68, Issue 2, March 2018 is now available online on Taylor & Francis Online

@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }

The online platform for Taylor & Francis Online content Acta Agriculturae Scandinavica, Section B — Soil & Plant Science, Volume 68, Issue 2, March 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: ORIGINAL ARTICLES Changes induced by plastic film mulches on soil temperature and their relevance in growth and fruit yield of pickling cucumber Vicente Torres-Olivar, Luis Ibarra-Jiménez, Antonio Cárdenas-Flores, Ricardo Hugo Lira-Saldivar, José Humberto Valenzuela-Soto & Marco Antonio Castillo-Campohermoso Pages: 97-103 | DOI: 10.1080/09064710.2017.1367836 Meta-analysis of experimental warming on soil invertase and urease activities Yinping Bai, Feng Li, Gang Yang, Shengwei Shi, Faqin Dong, Mingxue Liu, Xiaoqin Nie & Jiangbo Hai Pages: 104-109 | DOI: 10.1080/09064710.2017.1375140 Resistance breeding and biocontrol of Striga asiatica (L.) Kuntze in maize: a review Admire Tichafa Shayanowako, Mark Laing, Hussein Shimelis & Learnmore Mwadzingeni Pages: 110-120 | DOI: 10.1080/09064710.2017.1370493 Diversity assessment of sweetpotato germplasm collections for yield and yield-related traits in western Tanzania Filson Mbezi Kagimbo, Hussein Shimelis & Julia Sibiya Pages: 121-129 | DOI: 10.1080/09064710.2017.1372516 Low-P solution culture can be used for screening root growth vigor in soil for high nutrient uptake of spring wheat varieties Yaosheng Wang, Lars Stoumann Jensen & Jakob Magid Pages: 130-138 | DOI: 10.1080/09064710.2017.1367835 A new hoe share design for weed control: measurements of soil movement and draught forces during operation Liubava Znova, Bo Melander, Aleksander Lisowski, Jacek Klonowski, Jaroslaw Chlebowski, Gareth T. C. Edwards, Søren Kirkegaard Nielsen & Ole Green Pages: 139-148 | DOI: 10.1080/09064710.2017.1367837 Soil microbial communities changed with a continuously monocropped processing tomato system Yalong Kang, Feng Jing, Wenqinq Sun, Jianguo Liu & Guiying Jiang Pages: 149-160 | DOI: 10.1080/09064710.2017.1370124 Efficacy of fresh fruit from Cucumis myriocarpus as Nemarioc-AL phytonematicide on suppression of root-knot nematodes in tomato plant production P. E. Tseke & P. W. Mashela Pages: 161-165 | DOI: 10.1080/09064710.2017.1371792 Inoculant rhizobia suppressed root-knot disease, and enhanced plant productivity and nutrient uptake of some field-grown food legumes Mujeebur Rahman Khan, Fayaz A. Mohiddin & Faheem Ahamad Pages: 166-174 | DOI: 10.1080/09064710.2017.1374448 Yield and water use efficiency of dryland potato in response to plastic film mulching on the Loess Plateau Qiang Li, Hongbing Li & Suiqi Zhang Pages: 175-188 | DOI: 10.1080/09064710.2017.1377761 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Intermittent administration of PTH induces the expression of osteocalcin and BMP-2 on choroid plexus cells associated with suppression of sclerostin, TGF-β1, and Na + K + ATPase

http://ift.tt/2yhM4GR

Unusual cutaneous manifestation of dermatomyositis

http://ift.tt/2C3u3iy

Intermittent administration of PTH induces the expression of osteocalcin and BMP-2 on choroid plexus cells associated with suppression of sclerostin, TGF-β1, and Na + K + ATPase

http://ift.tt/2yhM4GR

Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign.

Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign.

Case Rep Endocrinol. 2017;2017:2390797

Authors: Herrero-Ruiz A, Villanueva-Alvarado HS, Corrales-Hernández JJ, Higueruela-Mínguez C, Feito-Pérez J, Recio-Cordova JM

Abstract
We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM) with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1). DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.

PMID: 29225978 [PubMed]

http://ift.tt/2AdkNXX

Serum Leptin, Resistin, and Adiponectin Concentrations in Psoriasis: A Meta-Analysis of Observational Studies

Background: Psoriasis is an immune-mediated, inflammatory disease. Adipokines contribute to the regulation of immune-mediated processes and inflammation. Objective: The aim of our study was to systematically review the literature for studies that have evaluated the circulating concentrations of adipokines in patients with psoriasis and controls and to meta-analyze the best evidence available. Methods: Eligible were studies that have assessed leptin, resistin, or adiponectin concentrations in psoriatic patients and a reference group. The study was conducted in adherence with the PRISMA standards. Results: Psoriatic patients had higher leptin concentrations compared to controls (random effects model, mean difference, MD = 5.64 ng/mL, 95% CI: 3.00-8.29, p I² = 95.9%). Psoriatic patients had higher resistin concentrations compared to controls (MD = 4.66 ng/mL, 95% CI: 2.62-6.69, p I² = 99.2%). Finally, psoriatic patients had lower adiponectin concentrations compared to controls (MD = -1.87 μg/mL, 95% CI: -2.76 to -0.98, p I² = 95.9%). Conclusion: The study supported the hypothesis that leptin and resistin concentrations are higher and adiponectin concentrations are lower in patients with psoriasis compared to controls. Hereby, the suggested pathogenic link between psoriasis and metabolic syndrome/obesity is reinforced and the role of comorbidities in psoriasis is highlighted.
Dermatology

http://ift.tt/2AuVeWf

DRESS et virus opinion d’experts : réponse

Publication date: Available online 11 December 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): V. Descamps




http://ift.tt/2B73k6y

Attractivité de la carrière hospitalo-universitaire en médecine : quels obstacles, quelles solutions ? L’avis des enseignants

Publication date: Available online 11 December 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): M. Samimi, B. Dreno, S. Aractingi, M. Beylot-Barry, C. Bodemer, O. Chosidow, B. Cribier, J.-P. Lacour, C. Paul, M.-A. Richard, C. Gaudy-Marqueste, A. Soria




http://ift.tt/2BDItJ5

Score and shave technique with freehand scalpel for harvesting small split-thickness skin grafts in dermatological surgery

http://ift.tt/2iTOB4P

Coexistence of pemphigus herpetiformis with extramammary Paget disease

http://ift.tt/2l42YaM

Perinatal Case Fatality Rate Related to Congenital Zika Syndrome in Brazil: a Cross-Sectional Study

Publication date: Available online 12 December 2017
Source:Pediatric Neurology
Author(s): Nilson N. Mendes Neto, Jessika Thais da Silva Maia, Marcelo Rodrigues Zacarkim, Igor Queiroz, Angelle Desiree Labeaud, David M. Aronoff




http://ift.tt/2nSUBQr

An Infectious Masquerader of Anaplastic Astrocytoma in a Child

Publication date: Available online 11 December 2017
Source:Pediatric Neurology
Author(s): Natalia Vélez-Tirado, Juan Esteban Cote-Orozco




http://ift.tt/2C87sl6

Hydrocephalus in Pediatric Traumatic Brain Injury: National Incidence, Risk Factors, and Outcomes in 124,444 Hospitalized Patients

Publication date: Available online 11 December 2017
Source:Pediatric Neurology
Author(s): Kavelin Rumalla, Vijay Letchuman, Kyle A. Smith, Paul M. Arnold
IntroductionHydrocephalus is a life-threatening sequela of traumatic brain injury (TBI) with poorly defined epidemiology in children. Here, we report the national incidence, risk factors, and outcomes associated with post-traumatic hydrocephalus (PTH).MethodsThe Kids Inpatient Database (2003, 2006, 2009, 2012) was queried using ICD-9-CM codes to identify all patients (age 0-20) with TBI (850.xx-854.xx) and non-congenital hydrocephalus (331.3-331.5, exclude 742.3). Variables included patient demographics and comorbidities, TBI severity (level of consciousness, injury type), treatment, and outcome-related measures. Risk factors associated with PTH were identified using univariate and multivariable analysis.ResultsPTH occurred in 1,265 (1.0%) of 124,444 patients hospitalized with TBI and was managed by ventriculoperitoneal shunt (32.7%) and extraventricular drain (10.7%). PTH had highest rates in shaken baby syndrome (6.7%, N=19) and firearm injury (3.4%, N=74). PTH varied by type of TBI: subdural hematoma (2.4%), subarachnoid hemorrhage (1.4%), epidural hematoma (1.0%), cerebral laceration (0.9%), concussion (0.2%). Multivariable risk factors for PTH included age 0-5 years-old (versus 6-20), Medicaid (versus private), electrolyte disorder, chronic neurological condition, weight loss, subarachnoid hemorrhage, subdural hematoma, open wound, postoperative neurological complication (iatrogenic stroke), and septicemia (P<0.05). PTH rates are higher amongst surgically managed patients (6.0% vs. 0.5%) unless managed within first 24 hours (0.8% vs. 4.1%) (P<0.05). PTH was associated with greater LOS (25 vs. 5 days) and hospital costs ($86,596 vs. $16,791), but lower mortality (1.1% vs. 5.4%).ConclusionPTH in children is relatively uncommon compared to adults. Risk factors identified here, including the influence of surgical intervention, warrant further investigation.



http://ift.tt/2nSUvZ5

Short Takes

Publication date: Available online 12 December 2017
Source:Pediatric Neurology
Author(s): Steven G. Pavlakis




http://ift.tt/2C3hSCm

Visual cortical activity before and after cochlear implantation: A follow up ERP prospective study in deaf children

Publication date: Available online 3 November 2017
Source:International Journal of Psychophysiology
Author(s): Scania de Schonen, Josiane Bertoncini, Nathalie Petroff, Vincent Couloigner, Thierry Van Den Abbeele
ERPs were recorded in response to presentation of static colored patterned stimuli in 25 children (19 to 80months of age at cochlear implantation, CI) with very early prelingual profound deafness (PreLD), 21 postlingual profoundly deaf children (PostLD) (34 to 180months of age at CI) and gender- and age-matched control hearing children. Recording sessions were performed before CI, then 6 and 24months after CI.Results showed that prelingual and, at a lesser degree, postlingual auditory deprivation altered cortical visual neural activity associated to colored shapes from both P1 and N1 cortical processing stages. The P1 and N1 amplitude modifications vanished about 24months after CI in both PreLD and PostLD deaf children. In PreLD the visual processing pattern becomes similar to the typical one essentially by an amplitude decrease of P1 on the left hemisphere together with an amplitude increase of the N1 on the right hemisphere. Finally, in PreLD, increased LH advantage over the RH in N1 amplitude on the cerebellar-occipito-parietal region before CI showed a significant inverse relationship with speech perception outcomes 3years after CI.Investigating early visual processing development and its neural substrates in deaf children would help to understand the variability of CI outcome, because their cortical visual organization diverged from the one of typically developing hearing children, and cannot be predicted from what is observed in deaf adults.



http://ift.tt/2kpbbT0

An uncommon cause of panniculitis

http://ift.tt/2knnsaC

Age-specific reference values and cut-off points for anti-müllerian hormone in infertile women following a long agonist treatment protocol for IVF

Abstract

Purpose

The aims of this study were to determining the reference value of anti-müllerian hormone (AMH) in infertile women and effect of AMH on different ovarian responses in the stratum of BMI categories.

Methods

Through a retrospective cohort study the information of 816 infertile patients referring to the referral infertility clinic of Mahdiyeh Hospital since the beginning of 2011 until the end of January 2016 were used. The normal-based method was undertaken to calculate age-specific AMH percentiles. To determine the effect of AMH on the outcomes of different ovarian responses following adjustment of associated variables, the multinomial regression model was used.

Results

Estimated reference intervals for AMH corresponding to the 2.5 and 97.5th‰ in patients with normal ovarian response are from 0.096 to 6.2 ng/mL. These values for percentiles of 5, 10, 25, 50, 75, 90, and 95% are, respectively, 0.18, 0.33, 0.77, 1.68, 3.05, 4.45, and 5.36 ng/dL. Also the reference value for the 20-year-old participants has a maximum range (0.12–7.64), while for 43-year-old ones has the lowest range (0.08–5.3). Among participants under and above 35 years old, the optimal cut-off points for predicting normal ovarian response are, respectively, 1.5 and 1.2 ng/dL. With each unit increase in the log of AMH concentration, the odds of having excessive ovarian response in patients with normal weight compared to that of having normal ovarian response is 32% higher.

Conclusions

Determining AMH reference values in IVF candidates allows specialists to measure only AMH plasma levels in IVF candidates so as to find whether or not the ovarian response is normal before applying other therapeutic measures; accordingly, they can adjust a treatment plan for each individual separately.

http://ift.tt/2l2Svg1

AML Therapy: Wake Up the Guardian and Cut Loose the Executioners

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Dario C. Altieri
In this issue of Cancer Cell, Pan et al. show that a combination therapy designed to reactivate the p53 tumor suppressor while antagonizing the anti-apoptotic function of Bcl-2 is highly active in preclinical models of refractory acute myeloid leukemia (AML). The results may move the needle in this hard-to-treat malignancy.

Teaser

In this issue of Cancer Cell, Pan et al. show that a combination therapy designed to reactivate the p53 tumor suppressor while antagonizing the anti-apoptotic function of Bcl-2 is highly active in preclinical models of refractory acute myeloid leukemia (AML). The results may move the needle in this hard-to-treat malignancy.


http://ift.tt/2jzdPcH

Genomic Biomarkers Predicting Response to Selective CDK4/6 Inhibition: Progress in an Elusive Search

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Geoffrey I. Shapiro
In this issue of Cancer Cell, Gong et al. have analyzed the sensitivity of 560 cell lines to the selective CDK4/6 inhibitor abemaciclib and have defined cancers with specific genomic "D-cyclin activating features (DCAF)" as particularly vulnerable. These findings will facilitate patient selection as development of this drug class continues.

Teaser

In this issue of Cancer Cell, Gong et al. have analyzed the sensitivity of 560 cell lines to the selective CDK4/6 inhibitor abemaciclib and have defined cancers with specific genomic "D-cyclin activating features (DCAF)" as particularly vulnerable. These findings will facilitate patient selection as development of this drug class continues.


http://ift.tt/2BgBpS8

Stressing Out PanIN: NRF2 Pushes over the Edge

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Laura Torrente, Gina M. DeNicola
The mechanisms by which chronic stress promote the development of pancreatic ductal adenocarcinoma (PDAC) are poorly defined. In this issue of Cancer Cell, Todoric et al. discover a role for impaired autophagy in the development of PDAC through p62-mediated activation of NRF2.

Teaser

The mechanisms by which chronic stress promote the development of pancreatic ductal adenocarcinoma (PDAC) are poorly defined. In this issue of Cancer Cell, Todoric et al. discover a role for impaired autophagy in the development of PDAC through p62-mediated activation of NRF2.


http://ift.tt/2jzdEhx

Glut3 Addiction: A Druggable Vulnerability in Glioblastoma

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Severa Bunda, Gelareh Zadeh, Kenneth D. Aldape
The link between GBM molecular subtype and response to treatment remains undefined. In this issue of Cancer Cell, Cosset and colleagues define a subpopulation of patients within the proneural/classical subtype sensitive to integrin blockade because of a Glut3 addiction. These findings reveal context-dependent druggable vulnerability in a subpopulation of GBM.

Teaser

The link between GBM molecular subtype and response to treatment remains undefined. In this issue of Cancer Cell, Cosset and colleagues define a subpopulation of patients within the proneural/classical subtype sensitive to integrin blockade because of a Glut3 addiction. These findings reveal context-dependent druggable vulnerability in a subpopulation of GBM.


http://ift.tt/2BdIYsQ

Inflammation, ROS, and Mutagenesis

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Asmaa El-Kenawi, Brian Ruffell
It has long been hypothesized that reactive oxygen species (ROS) are responsible for the association between chronic inflammatory diseases and increased tumor incidence. In this issue of Cancer Cell, Canli et al. now demonstrate that amplified ROS production specifically by myeloid cells is sufficient to promote intestinal mutagenesis.

Teaser

It has long been hypothesized that reactive oxygen species (ROS) are responsible for the association between chronic inflammatory diseases and increased tumor incidence. In this issue of Cancer Cell, Canli et al. now demonstrate that amplified ROS production specifically by myeloid cells is sufficient to promote intestinal mutagenesis.


http://ift.tt/2jwoyEE

Breaking Down Barriers to Chemoresistance: Role of Chemotherapy-Induced Osteoblastic Jagged1

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Khalid S. Mohammad, Theresa A. Guise
Bone metastases are incurable. The bone microenvironment has always been a suspect for this clinical enigma, but the exact mechanisms have been unclear. In this issue of Cancer Cell, Zheng and colleagues provide evidence that chemotherapy itself induces chemoresistance of bone metastases, mediated by osteoblast Jagged1-induced tumor Notch signaling.

Teaser

Bone metastases are incurable. The bone microenvironment has always been a suspect for this clinical enigma, but the exact mechanisms have been unclear. In this issue of Cancer Cell, Zheng and colleagues provide evidence that chemotherapy itself induces chemoresistance of bone metastases, mediated by osteoblast Jagged1-induced tumor Notch signaling.


http://ift.tt/2BdIN0E

Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Hanqiu Zheng, Yangjin Bae, Sabine Kasimir-Bauer, Rebecca Tang, Jin Chen, Guangwen Ren, Min Yuan, Mark Esposito, Wenyang Li, Yong Wei, Minhong Shen, Lanjing Zhang, Nikolai Tupitsyn, Klaus Pantel, Chadwick King, Jan Sun, Jodi Moriguchi, Helen Toni Jun, Angela Coxon, Brendan Lee, Yibin Kang
Bone metastasis is a major health threat to breast cancer patients. Tumor-derived Jagged1 represents a central node in mediating tumor-stromal interactions that promote osteolytic bone metastasis. Here, we report the development of a highly effective fully human monoclonal antibody against Jagged1 (clone 15D11). In addition to its inhibitory effect on bone metastasis of Jagged1-expressing tumor cells, 15D11 dramatically sensitizes bone metastasis to chemotherapy, which induces Jagged1 expression in osteoblasts to provide a survival niche for cancer cells. We further confirm the bone metastasis-promoting function of osteoblast-derived Jagged1 using osteoblast-specific Jagged1 transgenic mouse model. These findings establish 15D11 as a potential therapeutic agent for the prevention or treatment of bone metastasis.

Graphical abstract

Teaser

Zheng et al. develop 15D11, a fully human monoclonal antibody to Jagged1, which inhibits Jagged1 on breast cancer cells as well as blocking metastasis-promoting effects of osteoblast-derived Jagged1 induced by chemotherapy. 15D11 reduces bone metastasis and sensitizes metastases to chemotherapy in mouse models of breast cancer.


http://ift.tt/2jwoXqJ

Synthetic Lethality of Combined Bcl-2 Inhibition and p53 Activation in AML: Mechanisms and Superior Antileukemic Efficacy

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Rongqing Pan, Vivian Ruvolo, Hong Mu, Joel D. Leverson, Gwen Nichols, John C. Reed, Marina Konopleva, Michael Andreeff
Evasion of apoptosis is a hallmark of cancer. Bcl-2 and p53 represent two important nodes in apoptosis signaling pathways. We find that concomitant p53 activation and Bcl-2 inhibition overcome apoptosis resistance and markedly prolong survival in three mouse models of resistant acute myeloid leukemia (AML). Mechanistically, p53 activation negatively regulates the Ras/Raf/MEK/ERK pathway and activates GSK3 to modulate Mcl-1 phosphorylation and promote its degradation, thus overcoming AML resistance to Bcl-2 inhibition. Moreover, Bcl-2 inhibition reciprocally overcomes apoptosis resistance to p53 activation by switching cellular response from G1 arrest to apoptosis. The efficacy, together with the mechanistic findings, reveals the potential of simultaneously targeting these two apoptosis regulators and provides a rational basis for clinical testing of this therapeutic approach.

Teaser

Pan et al. show that p53 activation promotes Mcl-1 degradation, and Bcl-2 inhibition shifts the p53 activation response from G1 arrest to apoptosis. Combining p53 activation and Bcl-2 inhibition overcomes resistance to either alone and provides better therapeutic efficacy in mouse models of acute myeloid leukemia.


http://ift.tt/2jwoTat

Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Xueqian Gong, Lacey M. Litchfield, Yue Webster, Li-Chun Chio, Swee Seong Wong, Trent R. Stewart, Michele Dowless, Jack Dempsey, Yi Zeng, Raquel Torres, Karsten Boehnke, Cecilia Mur, Carlos Marugán, Carmen Baquero, Chunping Yu, Steven M. Bray, Isabella H. Wulur, Chen Bi, Shaoyou Chu, Hui-Rong Qian, Philip W. Iversen, Farhana F. Merzoug, Xiang S. Ye, Christoph Reinhard, Alfonso De Dios, Jian Du, Charles W. Caldwell, María José Lallena, Richard P. Beckmann, Sean G. Buchanan
Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3′UTR mutation associated with increased expression in endometrial cancer. The results suggest multiple additional classes of cancer that may benefit from CDK4/6-inhibiting drugs such as abemaciclib.

Teaser

Gong et al. identify a subset of cancers highly sensitive to CDK4/6 inhibition, which are characterized by various genomic aberrations known to elevate D-cyclin levels but not by CDKN2A mutations. They also identify a recurrent CCND1 3′UTR mutation associated with increased CCND1 expression in endometrial cancer.


http://ift.tt/2BdIBOY

mTORC2 Promotes Tumorigenesis via Lipid Synthesis

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Yakir Guri, Marco Colombi, Eva Dazert, Sravanth K. Hindupur, Jason Roszik, Suzette Moes, Paul Jenoe, Markus H. Heim, Isabelle Riezman, Howard Riezman, Michael N. Hall
Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis. Inhibition of fatty acid or sphingolipid synthesis prevented tumor development, indicating a causal effect in tumorigenesis. Increased levels of cardiolipin were associated with tubular mitochondria and enhanced oxidative phosphorylation. Furthermore, increased lipogenesis correlated with elevated mTORC2 activity and HCC in human patients. Thus, mTORC2 promotes cancer via formation of lipids essential for growth and energy production.

Graphical abstract

Teaser

Guri et al. find that mTORC2 promotes de novo fatty acid and lipid synthesis. This pathway is elevated in human liver cancer and drives hepatosteatosis and liver cancer in mice, whereas its inhibition or deletion of Rictor reduces mouse tumors, suggesting this pathway as a therapeutic target in liver cancer.


http://ift.tt/2jwolRS

MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Tianzhi Huang, Chung Kwon Kim, Angel A. Alvarez, Rajendra P. Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M. Horbinski, Songjian Lu, Roger Stupp, John A. Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P. Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy. Inhibiting ATG4B in combination with radiotherapy in treating mice with intracranial GBM xenograft markedly slows tumor growth and provides a significant survival benefit. Our work describes an MST4-ATG4B signaling axis that influences GBM autophagy and malignancy, and whose therapeutic targeting enhances the anti-tumor effects of radiotherapy.

Graphical abstract

Teaser

Huang et al. show that radiation induces MST4 expression and that MST4 phosphorylates ATG4B at serine 383, which increases ATG4B activity and autophagic flux. Inhibition of ATG4B reduces autophagy and tumorigenicity of glioblastoma (GBM) cells and improves the impact of radiotherapy on GBM growth in mice.


http://ift.tt/2jwol4k

Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Özge Canli, Adele M. Nicolas, Jalaj Gupta, Fabian Finkelmeier, Olga Goncharova, Marina Pesic, Tobias Neumann, David Horst, Martin Löwer, Ugur Sahin, Florian R. Greten
Increased oxidative stress has been suggested to initiate and promote tumorigenesis by inducing DNA damage and to suppress tumor development by triggering apoptosis and senescence. The contribution of individual cell types in the tumor microenvironment to these contrasting effects remains poorly understood. We provide evidence that during intestinal tumorigenesis, myeloid cell-derived H2O2 triggers genome-wide DNA mutations in intestinal epithelial cells to stimulate invasive growth. Moreover, increased reactive oxygen species (ROS) production in myeloid cells initiates tumor growth in various organs also in the absence of a carcinogen challenge in a paracrine manner. Our data identify an intricate crosstalk between myeloid cell-derived ROS molecules, oxidative DNA damage, and tumor necrosis factor α-mediated signaling to orchestrate a tumor-promoting microenvironment causing invasive cancer.

Graphical abstract

Teaser

Canli et al. show that excessive H2O2 produced by myeloid cells, independent of cytokines, transforms intestinal epithelial cells (IEC) by triggering genome-wide DNA mutations. H2O2 also induces IEC to secrete cytokines and chemokines, via a TNFα autocrine loop, to recruit myeloid cells for promotion of tumor invasion.


http://ift.tt/2jwoNj7

High-throughput Phenotyping of Lung Cancer Somatic Mutations

Publication date: 11 December 2017
Source:Cancer Cell, Volume 32, Issue 6
Author(s): Alice H. Berger, Angela N. Brooks, Xiaoyun Wu, Yashaswi Shrestha, Candace Chouinard, Federica Piccioni, Mukta Bagul, Atanas Kamburov, Marcin Imielinski, Larson Hogstrom, Cong Zhu, Xiaoping Yang, Sasha Pantel, Ryo Sakai, Jacqueline Watson, Nathan Kaplan, Joshua D. Campbell, Shantanu Singh, David E. Root, Rajiv Narayan, Ted Natoli, David L. Lahr, Itay Tirosh, Pablo Tamayo, Gad Getz, Bang Wong, John Doench, Aravind Subramanian, Todd R. Golub, Matthew Meyerson, Jesse S. Boehm




http://ift.tt/2jwoGnH

Factors Associated With Lack of Vision Improvement in Children With Cortical Visual Impairment

Background: Improvement in vision has been noted in children with cortical visual impairment (CVI), resulting from disparate types of brain injury. The purpose of our study was to determine the risk factors associated with poor recovery of vision in this group of patients. Methods: Case records of children who were born before 2010 with at least 4 follow-up visits for CVI were reviewed for underlying etiologies of CVI, visual acuity (VA), and associated neurological and ophthalmological disorders. VA was assessed in 6 qualitative grades. Changes in VA were recorded as the difference between the grades of VA at presentation and the last follow-up visit. The outcome was calculated as a ratio of actual improvement to potential improvement in grades of qualitative VA. Multiple linear regression determined factors associated with lack of vision improvement in all children and based on etiology. Results: Fifty-three children with CVI were identified. The median age at presentation was 13.6 months (range: 2.9–76.4 months) and the median follow-up was 5.8 years (1.1–16.3 years). CVI resulted from central nervous system (CNS) malformation (9.4%), hypoxic/inflammatory injury (15.1%), seizures (24.5%), and combined causes (51.0%). Vision improvement was noted in 83% of children. Lack of VA improvement was associated with older age at presentation in all children with CVI and within each etiological group except CNS malformation. None of the other investigated variables were associated with poor recovery of VA. Conclusions: Most of the children with CVI showed improvement in vision. Older age at presentation, but not etiology of CVI, was associated with poor improvement in VA. Address correspondence to Swati Handa, FRCS, MCI, Pediatric Ophthalmology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899; E-mail: Handa.swati@kkh.com.sg The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (http://ift.tt/2BFTkP1). © 2017 by North American Neuro-Ophthalmology Society

http://ift.tt/2C874TJ