Head and Neck Diseases by Alexandros G.Sfakianakis: 03/14/18

Τετάρτη 14 Μαρτίου 2018

Editorial Board

Publication date: April 2018
Source:Dental Materials, Volume 34, Issue 4

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A Sub-population of Group A Streptococcus Elicits a Population-wide Production of Bacteriocins to Establish Dominance in the Host

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Baruch B. Hertzog, Yael Kaufman, Debabrata Biswas, Miriam Ravins, Poornima Ambalavanan, Reuven Wiener, Veronique Angeli, Swaine L. Chen, Emanuel Hanski
Bacteria use quorum sensing (QS) to regulate gene expression. We identified a group A Streptococcus (GAS) strain possessing the QS system sil, which produces functional bacteriocins, through a sequential signaling pathway integrating host and bacterial signals. Host cells infected by GAS release asparagine (ASN), which is sensed by the bacteria to alter its gene expression and rate of proliferation. We show that upon ASN sensing, GAS upregulates expression of the QS autoinducer peptide SilCR. Initial SilCR expression activates the autoinduction cycle for further SilCR production. The autoinduction process propagates throughout the GAS population, resulting in bacteriocin production. Subcutaneous co-injection of mice with a bacteriocin-producing strain and the globally disseminated M1T1 GAS clone results in M1T1 killing within soft tissue. Thus, by sensing host signals, a fraction of a bacterial population can trigger an autoinduction mechanism mediated by QS, which acts on the entire bacterial community to outcompete other bacteria within the infection.

Graphical abstract

Teaser

Pathogenic bacteria evolved exquisite systems to sense their hosts and adjust their responses to ensure their survival and propagation. Hertzog, Kaufman et al. report that GAS produces bacteriocins through a sequential signaling pathway, integrating host and bacterial signals. Bacteriocins kill other bacteria within the infection, enabling GAS to establish dominance.

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Evaluation of biofilm formation on novel copper-catalyzed azide-alkyne cycloaddition (CuAAC)-based resins for dental restoratives

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Publication date: April 2018
Source:Dental Materials, Volume 34, Issue 4
Author(s): Sheryl Zajdowicz, Han Byul Song, Austin Baranek, Christopher N. Bowman
ObjectiveFor the past several decades, the resins used in dental restorations have been plagued with numerous problems, including their implication in biofilm formation and secondary caries. The need for alternative resins is critical, and evaluation of biofilm formation on these resins is essential. The aim of this study was to evaluate in vitro biofilm formation on the surface of novel copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)-based resins and composites.MethodsCuAAC-based resins/composites made from varying azide monomers and different copper concentrations were compared with BisGMA-TEGDMA resins/composites that served as the control. Biofilms were formed using a mono-species model containing a luciferase-expressing strain of Streptococcus mutans. Luciferase activity was measured and the number of viable bacteria was enumerated on biofilms associated with each resin and composite.ResultsA significant reduction (p<0.05) in luciferase activity, and the number of viable bacteria recovered from biofilms on CuAAC-based resins and composites was observed in comparison to biofilms associated with the BisGMA-TEGDMA controls.SignificanceCuAAC-based resins do still allow for the formation of biofilms; however, the statistically significant reduction of growth that was associated with the CuAAC resin may enhance the longevity of restorations that incorporate CuAAC-based materials.

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Surface characteristics and biocompatibility of cranioplasty titanium implants following different surface treatments

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Publication date: April 2018
Source:Dental Materials, Volume 34, Issue 4
Author(s): Muhanad M. Hatamleh, Xiaohong Wu, Ahmad Alnazzawi, Jason Watson, David Watts
ObjectiveSurface and mechanical properties of titanium alloys are integral for their use in restoring bone defects of skull and face regions. These properties are affected by the method of constructing and surface treatment of the titanium implant. This study aimed to investigate the effects of titanium finishing protocols on the surface morphology, hardness and biocompatibility of TiAl6V4.MethodsSquare shaped TiAl6V4 specimens (ASTM F68) (10×10×0.5mm) were divided into seven groups of different surface treatments (n=10). The treatments included mechanical polishing, sandblasting with AL2O3 (50μm), immersion in different acids, and/or electro-chemical anodization. Weight loss %; 3D micro-roughness; Knoop micro-hardness, and osteoblast cell attachment and proliferation (after 3 days) were determined for each specimen. Data was analysed using one way ANOVA and Dunett T3 post-hoc tests, and t-test (p<0.05).ResultsWeight loss % was in the range of 1.70–5.60 as mechanical polishing produced the highest weight loss, followed by sandblasting, and combined protocol of mechanical polishing and acid treatment (p<0.05). Micro-roughness values (μm) were in the range of 2.81–16.68. It was the highest for control specimens (p<0.05), and smoothest surfaces after combined mechanical polishing and acid treatment; or after electro-chemical treatment (p<0.05). Micro-hardness values (MPa) ranged 170.90–442.15 as sandblasting with/without acid treatment caused statically significantly the highest values (p<0.05) while control and mechanically polished specimens had the lowest values (p<0.05). All treatments produced equally biocompatible surfaces (p>0.05) after 1h or 3 days. Furthermore, osteoblast cell proliferation statistically significantly increased after 3days among each surface treatment (p<0.05).SignificanceDifferent finishing treatments have variable effect on cranioplasty titanium surface loss, micro-roughness and micro-hardness but constant improved biocompatibility effect. Electro-chemical treatment caused less material loss and produced biocompatible smoothest surface of comparable hardness; hence it can be suitable for cranioplasty titanium surface finishing.

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Polymerization efficiency affects interfacial fracture toughness of adhesives

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Publication date: April 2018
Source:Dental Materials, Volume 34, Issue 4
Author(s): Pong Pongprueksa, Jan De Munck, Masanao Inokoshi, Bart Van Meerbeek
ObjectiveTo evaluate the effect of the kind and concentration of photo-initiator on the degree of conversion (DC) of adhesives on dentin/glass substrates and their mini-interfacial fracture toughness (mini-iFT) to dentin.MethodsWe tested the adhesive Clearfil S³ Bond Plus and 4 derived experimental 'LUB' ('Leuven Univesity Bond') adhesives (all from Kuraray Noritake), namely 'LUB-CQ/amine_high', 'LUB-CQ/amine_low', 'LUB-TPO_high', and 'LUB-TPO_low', respectively containing 2.0wt% camphorquinone (CQ) and 2.0wt% EDMAB (amine), 0.35wt% CQ and 0.35wt% amine, 2.0wt% TPO, and 0.35wt% TPO. For DC, each adhesive was applied onto glass or dentin prior to being cured (Bluephase 20i; Ivoclar Vivadent: "high mode") for 10s. DC was measured at 5min, 10min, 1h, 24h and 1 week using micro-Raman spectroscopy (SENTERRA; BrukerOptik). For mini-iFT, each adhesive was bonded to 320-grit SiC-paper ground dentin and covered with composite (Z100; 3M ESPE). The restored teeth were cut in sticks (1.5×2.0×16mm), after which a single-gradient notch was prepared at the adhesive-dentin interface using a 150-μm diamond blade. The micro-specimens were loaded until failure in a 4-point bending test and the mini-iFT in term of KQvM was calculated.ResultsDC was higher on dentin than on glass. All adhesives were adequately polymerized at 1 week, except for LUB-TPO_low. DC at 5min was significantly higher for LUB-TPO_high than for both CQ/amine-based adhesives. The highest and most reliable mini-iFT was measured for LUB-CQ/amine_high, despite its 5-min DC was relatively low. No correlation between DC and mini-iFT was found.SignificanceCuring of TPO-based adhesives is faster, but the dark cure of the CQ/amine-containing adhesives is more efficient. The differences in curing profiles do affect the mechanical properties of the resultant interfaces at dentin.

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44Ca doped remineralization study on dentin by isotope microscopy

Publication date: April 2018
Source:Dental Materials, Volume 34, Issue 4
Author(s): N. Hiraishi, S. Kobayashi, H. Yurimoto, J. Tagami
ObjectiveThe dental caries is developed as a result of an alternative course of mineral gain and loss. In order to distinguish between intrinsic Ca (tooth-derived mineral) and extrinsic Ca (solution-derived mineral) uptakes, a ⁴⁴Ca doped pH-cycling was performed using ⁴⁴Ca (a stable calcium isotope) remineralization solution.MethodsThe natural abundance of ⁴⁰Ca and ⁴⁴Ca is 96.9% and 2.1%, respectively. The remineralization solution was prepared using ⁴⁴Ca to contain 1.5mmol/L CaCl2 (⁴⁴Ca), 0.9mmol/L KH2PO4, 130mmol/L KCl, 20mmol/L HEPES at pH 7.0. The pH-cycling was conducted on bovine root dentin daily by demineralization (pH 5.0) for 2h, incubation in 0% (control) and 0.2% NaF (900ppm fluoride) for 2h and ⁴⁴Ca doped remineralization for 20h. After 14days pH-cycling, the specimens were sectioned longitudinally. On the sectioned surface, isotope imaging of ⁴⁰Ca and ⁴⁴Ca labeled mineral distribution was observed by a high mass-resolution stigmatic secondary ion 77 (Camera IMS 1270, Gennevilliers Cedex, France).ResultsUptake of ⁴⁴Ca was greater in intensity for the 0.2% fluoride group than the control, especially in the superficial lesions. The control group showed ⁴⁰Ca (intrinsic) distribution in the subsurface lesions and in the superficial lesions, meanwhile the fluoride group showed ⁴⁰Ca distribution limited in subsurface lesions. The total Ca (⁴⁴Ca+⁴⁰Ca) image revealed more homogeneously for the control than the fluoride group.SignificanceSince the fluoride-treated surface is more acid-resistant than intrinsic dentin, alternative minerals were dissolved from the intact intrinsic lesion in the demineralization cycle.

Graphical abstract

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Shining a light on high volume photocurable materials

Publication date: Available online 14 March 2018
Source:Dental Materials
Author(s): William M. Palin, Julian G. Leprince, Mohammed A. Hadis
Spatial and temporal control is a key advantage for placement and rapid setting of light-activated resin composites. Conventionally, placement of multiple thin layers (<2mm) reduces the effect of light attenuation through highly filled and pigmented materials to increase polymerisation at the base of the restoration. However, and although light curing greater than 2mm thick layers is not an entirely new phenomenon, the desire amongst dental practitioners for even more rapid processing in deep cavities has led to the growing acceptance of so-called "bulk fill" (4–6mm thick) resin composites that are irradiated for 10–20s in daily clinical practice. The change in light transmission and attenuation during photopolymerisation are complex and related to path length, absorption properties of the photoinitiator and pigment, optical properties of the resin and filler and filler morphology. Understanding how light is transmitted through depth is therefore critical for ensuring optimal material properties at the base of thick increments. This article will briefly highlight the advent of current commercial materials that rationalise bulk filling techniques in dentistry, the relationship between light transmission and polymerisation and how optimal curing depths might be achieved.

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Bacterial Call to Arms for Warfare at the Infection Site

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Vitor Cabral, Karina B. Xavier
Bacterial sensing is important for perceiving environmental cues and activating responses. In this issue of Cell Host & Microbe, Hertzog et al. (2018) show that group A Streptococcus can couple the ability to respond to host cues with autoinduction of a quorum sensing system, leading to killing of bacterial competitors.

Teaser

Bacterial sensing is important for perceiving environmental cues and activating responses. In this issue of Cell Host & Microbe, Hertzog et al. (2018) show that group A Streptococcus can couple the ability to respond to host cues with autoinduction of a quorum sensing system, leading to killing of bacterial competitors.

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Lipid Catabolism Fuels Drosophila Gut Immunity

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Ambra Masuzzo, Julien Royet
Immune responses and metabolic regulation are tightly coupled in animals, but the underlying mechanistic connections are not fully understood. In this issue of Cell Host & Microbe, Lee et al. (2018) reveal how sustained ROS production in the gut depends on an upstream metabolic switch.

Teaser

Immune responses and metabolic regulation are tightly coupled in animals, but the underlying mechanistic connections are not fully understood. In this issue of Cell Host & Microbe, Lee et al. reveal how sustained ROS production in the gut depends on an upstream metabolic switch.

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Templating Antiviral RNAi in Insects

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Yanhong Han, Qingfa Wu, Shou-Wei Ding
Virus-specific small interfering RNAs (siRNAs) are a central component of antiviral responses in insects. In this issue of Cell Host & Microbe, Poirier et al. (2018) demonstrate that virus-infected flies and mosquitoes produce virus-derived extrachromosomal circular DNAs that serve as a template for the biogenesis of antiviral siRNAs.

Teaser

Virus-specific small interfering RNAs (siRNAs) are a central component of antiviral responses in insects. In this issue of Cell Host & Microbe, Poirier et al. (2018) demonstrate that virus-infected flies and mosquitoes produce virus-derived extrachromosomal circular DNAs that serve as a template for the biogenesis of antiviral siRNAs.

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A Sleeping Area of Malaria Research Awakes

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Elizabeth A. Winzeler
Phenotypic screening methods have had a profound impact on antimalarial drug development, but assays that predict which compounds might provide a radical cure have remained elusive. In this issue of Cell Host & Microbe, Gural et al. (2018) report hypnozoite culturing and systems to study these elusive, yet deadly, parasites.

Teaser

Phenotypic screening methods have had a profound impact on antimalarial drug development, but assays that predict which compounds might provide a radical cure have remained elusive. In this issue of Cell Host & Microbe, Gural et al. (2018) report hypnozoite culturing and systems to study these elusive, yet deadly, parasites.

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How Good Roommates Can Protect against Microbial Sepsis

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Rudi Beyaert, Claude Libert
In this issue of Cell Host & Microbe, Wilmore et al. (2018) co-housed isogenic mouse populations, uncovering commensal bacteria-induced serum IgA and IgA-producing bone marrow plasma cells as critical components of resistance against sepsis. They further identified gut microbial taxa that may account for the induction of this protective system.

Teaser

In this issue of Cell Host & Microbe, Wilmore et al. (2018) co-housed isogenic mouse populations, uncovering commensal bacteria-induced serum IgA and IgA-producing bone marrow plasma cells as critical components of resistance against sepsis. They further identified gut microbial taxa that may account for the induction of this protective system.

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The β2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F. Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the β2 integrin Mac-1 (CR3, integrin αMβ2), a receptor recognizing diverse microbial ligands. Interaction of L.m. with Mac-1 induces acid sphingomyelinase-mediated changes in membrane lipid composition that facilitate assembly and activation of the phagocyte NAPDH oxidase Nox2. Nox2-derived reactive oxygen species then trigger LC3 recruitment to L.m.-containing phagosomes by LAP. By promoting fusion of L.m.-containing phagosomes with lysosomes, LAP increases exposure of L.m. to bactericidal acid hydrolases, thereby enhancing anti-listerial activity of macrophages and immunity of mice.

Graphical abstract

Teaser

Listeria monocytogenes are targeted by the autophagic machinery via unclear molecular mechanisms. Gluschko and Herb et al. demonstrate that LC3-associated phagocytosis, but not canonical autophagy, is required for elimination of L. monocytogenes by macrophages and activated by the β2 integrin Mac-1 (CR3, integrin αMβ2).

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Reshaping of the Dendritic Cell Chromatin Landscape and Interferon Pathways during HIV Infection

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Jarrod S. Johnson, Sasha Y. Lucas, Lynn M. Amon, Stephanie Skelton, Rodolfo Nazitto, Sara Carbonetti, D. Noah Sather, Dan R. Littman, Alan Aderem
Myeloid dendritic cells (DCs) have the innate capacity to sense pathogens and orchestrate immune responses. However, DCs do not mount efficient immune responses to HIV-1, primarily due to restriction of virus reverse transcription, which prevents accumulation of viral cDNA and limits its detection through the cGAS-STING pathway. By allowing reverse transcription to proceed, we find that DCs detect HIV-1 in distinct phases, before and after virus integration. Blocking integration suppresses, but does not abolish, activation of the transcription factor IRF3, downstream interferon (IFN) responses, and DC maturation. Consistent with two stages of detection, HIV-1 "primes" chromatin accessibility of innate immune genes before and after integration. Once primed, robust IFN responses can be unmasked by agonists of the innate adaptor protein, MyD88, through a process that requires cGAS, STING, IRF3, and nuclear factor κB. Thus, HIV-1 replication increases material available for sensing, and discrete inflammatory inputs tune cGAS signaling to drive DC maturation.

Graphical abstract

Teaser

Parameters regulating the innate immune response to HIV-1 remain unclear. Johnson et al. elucidate how dendritic cells sense HIV-1 in two stages. They demonstrate that cGAS/STING signaling can be tuned through unrelated pathways to unmask interferon responses before and after HIV-1 integration.

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Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Yasmine Baktash, Anisha Madhav, Kelly E. Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms. HCV initially localizes with the early entry factors SR-B1, CD81, and EGFR at the basolateral membrane and then accumulates at the tight junction in an actin-dependent manner. HCV associates with CLDN1 and then OCLN at the tight junction and is internalized via clathrin-mediated endocytosis by an active process requiring EGFR. Thus, HCV uses a dynamic and multi-step process to engage and enter host cells.

Graphical abstract

Teaser

HCV entry is complex and involves multiple host factors. By imaging the infection of polarized hepatoma organoids with fluorescent HCV virions, Baktash et al. define the sequence of events during entry. They determine that HCV virions traffic with early receptors to tight junctions and then internalize in an EGFR-dependent manner.

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Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells

Publication date: 14 March 2018
Source:Cell Host & Microbe, Volume 23, Issue 3
Author(s): Liam Chung, Erik Thiele Orberg, Abby L. Geis, June L. Chan, Kai Fu, Christina E. DeStefano Shields, Christine M. Dejea, Payam Fathi, Jie Chen, Benjamin B. Finard, Ada J. Tam, Florencia McAllister, Hongni Fan, Xinqun Wu, Sudipto Ganguly, Andriana Lebid, Paul Metz, Sara W. Van Meerbeke, David L. Huso, Elizabeth C. Wick, Drew M. Pardoll, Fengyi Wan, Shaoguang Wu, Cynthia L. Sears, Franck Housseau

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Soil uranium concentration at Ranger Uranium Mine Land Application Areas drives changes in the bacterial community

Publication date: September 2018
Source:Journal of Environmental Radioactivity, Volume 189
Author(s): Saqib Mumtaz, Claire Streten, David L. Parry, Keith A. McGuinness, Ping Lu, Karen S. Gibb
Soil microorganisms may respond to metal stress by a shift in the microbial community from metal sensitive to metal resistant microorganisms. We assessed the bacterial community from low (2–20 mg kg⁻¹), medium (200–400 mg kg⁻¹), high (500–900 mg kg⁻¹) and very high (>900 mg kg⁻¹) uranium soils at Ranger Uranium Mine in northern Australia through pyrosequencing. Proteobacteria (28.85%) was the most abundant phylum at these sites, followed by Actinobacteria (9.31%), Acidobacteria (7.33%), Verrucomicrobia (2.11%), Firmicutes (2.02%), Chloroflexi (1.11%), Cyanobacteria (0.93%), Planctomycetes (0.82%), Bacteroidetes (0.46%) and Candidate_division_WS3 (Latescibacteria) (0.21%). However, 46.79% of bacteria were unclassified. Bacteria at low U soils differed from soils with elevated uranium. Bacterial OTUs closely related to Kitasatospora spp., Sphingobacteria spp. and Rhodobium spp. were only present at higher uranium concentrations and the bacterial community also changed with seasonal and temporal changes in soil uranium and physicochemical variables. This study using next generation sequencing in association with environmental variables at a uranium mine has laid a foundation for further studies of soil-microbe-metal interactions which may be useful for developing sustainable management and rehabilitation strategies. Furthermore, bacterial species associated with higher uranium may serve as useful indicators of uranium contamination in the wet-dry tropics.

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Perioperative Cardiac Arrest: Focus on Local Anesthetic Systemic Toxicity (LAST) Erratum

No abstract available

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Percutaneous Dilatational Tracheostomy Using Tube Exchanger

We describe a modified technique for percutaneous dilatational tracheostomy using a 15F tube exchanger or Eschmann catheter. A retrospective review of 1180 procedures using this modified technique demonstrated it to be effective with a failure rate of only 0.25% (3 patients). Moreover, it provides an additional safeguard with the ability to rapidly reintroduce the endotracheal tube into the trachea guided by the exchange catheter in the event of accidental extubation during the procedure. This technique needs no additional special devices or equipment (eg, a bronchoscope). However, a prospective study is needed to better define its complication rate. Accepted for publication January 22, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Ohad Ronen, MD, Department of Otolaryngology, Head and Neck Surgery, Galilee Medical Center, POB 21, Nahariya 2210001, Israel. Address e-mail to ohadr@gmc.gov.il. © 2018 International Anesthesia Research Society

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Burnout in American Anesthetists, Comparison With a French Cohort

No abstract available

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Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-Up Study Over an 11-Year Period in a Comprehensive Cancer Center

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France. Patients were followed from March 2006 to April 2017. Patients were selected for IDDS based on multidisciplinary meeting discussion. All IDDS-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed according to painful metameric level. Postimplant assessment of pain was determined using a numerical rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly until death. Pain scores were compared using the Wilcoxon signed rank test. Overall survival (OS) was estimated using the Kaplan–Meier method and compared between groups by log rank tests. RESULTS: Ninety-three patients received IDDS, and total therapy duration accounts for 10,300 IDDS days. Implanted patients suffered from severe pain before implantation (median presurgical NRS, 8 [interquartile range, 7–9]) despite a median 360 mg (260–600) oral morphine equivalent daily dose. Median OS in the whole cohort after intrathecal treatment start was 82 days (95% confidence interval, 59–95). Median OS after surgery for implantable pump was 91 days (83–111) and for external pump 27 days (20–49; P

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In Response

No abstract available

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Anesthesia for Percutaneous Pulmonary Valve Implantation: A Case Series

BACKGROUND: Twenty percent of patients born with congenital heart disease present with right ventricular outflow tract abnormalities. These patients require multiple surgical procedures in their lifetime. Transcatheter pulmonary valve replacement (TPVR) has become a viable alternative to conventional pulmonary valve and right ventricular outflow tract surgery in pediatric and adult populations. In this retrospective review, we analyze the perioperative management of adult patients who underwent TPVR in our center. METHODS: The study consisted of a chart review of patients who underwent TPVR at Toronto General Hospital between 2006 and 2015. Information about preoperative assessment, intraoperative anesthetic management, and intra- and postprocedural complications was collected. Two types of percutaneous valves have been used for a conduit or valve size between 16 and 28 mm. These procedures are done via the femoral, jugular, or subclavian vein under general anesthesia. RESULTS: Seventy-nine adults (17–68 years of age) who underwent elective TPVR procedures were included. General anesthesia was used in all cases. Defibrillation was necessary in 1 case, and bradycardia was spontaneously resolved in another 1. Eighty-five percent were successfully extubated at the end of the procedure. Five patients required intraoperative inotropic support. Three patients presented self-resolved hemoptysis. Mechanical ventilation for >24 hours was necessary in 3 cases, 2 of which also required concomitant inotropic support. Four failed deployments and 1 case of persistent conduit stenosis were reported. Three patients required reintubation. All patients were discharged home. CONCLUSIONS: Patients undergoing TPVR represent a complex and heterogeneous population. General anesthesia with endotracheal intubation is preferred. Setup for urgent lung isolation and cardiac defibrillation should be considered. Postoperative monitoring and intensive care setting are required. Anesthesiologists with cardiac anesthesia training are probably better suited to manage these patients. Accepted for publication January 22, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Massimiliano Meineri, MD, Department of Anesthesia and Pain Management, Toronto General Hospital, 200 Elizabeth St, EN3-400, Toronto, ON M5G 2C4, Canada. Address e-mail to massimiliano.meineri@uhn.ca. © 2018 International Anesthesia Research Society

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Protective Effect of Punica granatum Extract in Head and Neck Cancer Patients Undergoing Radiotherapy

Abstract

In India, head and neck cancers account for 30–40% cancers of all sites. Due to lack of screening program, wide variation in the availability of infrastructures and expertise, patients present at an advanced stage. The main stay of management of the head and neck tumours is surgery and chemoradiation. Radiation dermatitis and mucositis is one of the most common side effect encountered during the radiotherapy. Aim of our study was to study protective role of pomegranate extract on radiation induced dermatitis and mucositis in head and neck cancer patients. It was a prospective, clinical, double blind, case control study. 60 patients (30 active and controls) undergoing radiotherapy for head and neck cancer were studied for 12 months. Patients in study group were given whole fruit pomegranate extract. Each capsule contained 300 mg of whole fruit extract, each capsule contains 40% polyphenols and 27% punicalagin. Each patient were given 2 capsules every day for a period of 6–7 weeks. The skin and mucosal changes was graded according to the acute radiation morbidity scoring criteria (RTOG) for skin and mucous membrane. The results were statistically significant. Pomegranate extract proved to be radioprotective. Our study is one of the first study in humans to demonstrate the effectiveness of pomegranate extract in preventing radiation dermatitis and mucositis.

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ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma

Abstract

Background

Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.

Methods

The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signaling pathways were investigated in vitro.

Results

The patients were well-controlled and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signaling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.

Conclusions

The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signaling pathways. This provides a new understanding of glucocorticoid application in regards to allergic diseases.

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Can Vagus Nerve Stimulation improve Social Cognition in Autism?

Publication date: Available online 15 March 2018
Source:Cortex
Author(s): Ashwin Kumaria, Murugan Sitaraman

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Color Doppler Twinkling Artifact in Diagnosis of Tuberculous Pleuritis: A Comparison with Gray-Scale Ultrasonography and Computed Tomography

Publication date: Available online 14 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Jiakai Tian, Liang Xu
The aim of this study was to determine whether twinkling artifact (TA) detected on color Doppler ultrasonography can effectively determine the presence of pleural calcification compared with computed tomography (CT) and differentiate tuberculous pleuritis (TP) and cancerous pleuritis (CP). One hundred six cases of TP and 26 cases of CP were scanned using gray-scale ultrasonography (GSU) and TA to determine the presence of pleural calcification. With CT as the reference standard, 63.3% and 79.6% of patients with pleural calcification were identified with GSU and TA, respectively. The detection rate of TA was higher than that of GSU (p = 0.039). For the whole study population, 37.1% were identified as having pleural calcification with CT, significantly higher than the proportion detected with GSU (25.8%, p = 0.001), but not different from that detected with TA (41.7%, p = 0.327). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TA were 79.6%, 80.7%, 80.3%, 70.9% and 87.0%, respectively. The detection rate of TA was significantly higher than that of GSU (p < 0.001). When GSU was combined with TA (GSUTA), the positive rate in the TP group was significantly higher than that in the CP group (χ² < 0.001). In conclusion, TA is comparable to CT and more sensitive than GSU in the detection of pleural calcification. Evaluation for GSUTA on pleura may help to differentiate TP from CP.

http://ift.tt/2Dr5U52

Pre-Treatment with Either L-Carnitine or Piracetam Increases Ultrasound-Mediated Gene Transfection by Reducing Sonoporation-Associated Apoptosis

Publication date: Available online 14 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Wei-Hao Liao, Chueh-Hung Wu, Wen-Shiang Chen
Sonoporation, the use of ultrasound to alter the permeability of cell membranes, is a non-viral technique used to facilitate gene delivery, possibly by opening transient pores in the cell membrane. However, sonoporation may have negative bio-effects on cells, such as causing apoptosis, which limits its efficacy in gene delivery. In this study, we investigated whether pre-treatment with either L-carnitine or piracetam could protect cells from undergoing apoptosis after sonoporation and the possible mechanisms. We found that either L-carnitine or piracetam can promote gene transfection without reducing cell viability, possibly by reducing cavitation-induced reactive oxygen species generation, reversing alterations of mitochondrial membrane potential, preventing caspase-3/7 activity and facilitating mitochondrial ATP production. In conclusion, pre-treatment with either L-carnitine or piracetam could protect cells from sonoporation-associated apoptosis by preserving mitochondrial function.

http://ift.tt/2pbLCIs

Electroretinogram evaluation for the treatment of proliferative diabetic retinopathy by short-pulse pattern scanning laser panretinal photocoagulation

Abstract

Panretinal photocoagulation (PRP) is a standard method for proliferative diabetic retinopathy (PDR) treatment. However, conventional PRP usually significantly damages the retinal structure and vision. Retinal pattern scanning laser (PASCAL) photocoagulation has emerged as a new technique with fewer complications for the treatment of retinal disorders. This study compares the therapeutic effects of short-pulse PASCAL to conventional single-spot PRP for PDR. Fifty-two PDR patients (104 eyes) were randomly assigned into a short-pulse PASCAL-PRP treatment (SP) group and a conventional PRP treatment (TP) group. The best corrected visual acuity (BCVA) and full-field flash electroretinogram (ERG) data were evaluated before and after the two treatments. The BCVA data between before and after the PRP treatments did not show any significant difference. After the PRP treatment, the b-wave amplitude (b-A) in the dark-adapted 3.0 ERG (p = 0.0005) and the amplitude in the light-adapted 3.0 flicker ERG (p = 0.009) were significantly higher in the SP group compared with that of the TP group. In addition, after the PRP treatment, the a-wave implicit time (a-T) of light-adapted 3.0 ERG prolonged significantly in the TP group compared to the SP group. Compared with the parameters before the treatments, the a-A and b-A under dark-adapted 3.0 ERG and the b-A under the light-adapted 3.0 ERG in both TP and SP groups after the treatments decreased significantly (p < 0.05). Short-pulse PASCAL-PRP significantly attenuated partial vision damage compared to conventional PRP, although it still caused limited retinal injury and mild reduction in retinal function. These findings suggest that short-pulse PASCAL-PRP is a promising technique for PDR treatment.

http://ift.tt/2IsA4II

2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity

Abstract

Background

Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, three isoforms have been identified. Their allergenicity has not been elucidated.

Objective

This study investigated the allergenicity of Ara h 7 isoforms compared to Ara h 2 and 6.

Methods

Sensitization of 15 DBPCFC confirmed peanut allergic patients to recombinant Ara h 2.0201, 6.01 and isoforms of recombinant Ara h 7 was determined by IgE immunoblotting strips. A basophil activation test (BAT) was performed in nine patients to determine IgE-crosslinking capacities of the allergens. Sensitivity to the allergens was tested in five patients that were sensitized to at least one Ara h 7 isoform, by a concentration range in the BAT. 3D-prediction models and sequence alignments were used to visualize differences between isoforms and to predict allergenic epitope regions.

Results

Sensitization to Ara h 7.0201 was most frequent (80%) and showed to be equally potent as Ara h 2.0201 and 6.01 in inducing basophil degranulation. Sensitization to Ara h 7.0201 together with Ara h 2.0201 and/or 6.01 was observed, indicating the presence of unique epitopes compared to the other two isoforms. Differences between the three Ara h 7 isoforms were observed in C-terminal cysteine residues, pepsin and trypsin cleavage sites and three single amino acid substitutions.

Conclusion & clinical relevance

The majority of peanut-allergic patients are sensitized to isoform Ara h 7.0201, which is functionally as active as Ara h 2.0201 and 6.01. Unique epitopes are most likely located in the C-terminus or an allergenic loop region which is a known allergenic epitope region for Ara h 2.0201 and 6.01. Due to its unique epitopes and allergenicity, it is an interesting candidate to improve the diagnostic accuracy for peanut allergy.

http://ift.tt/2pcDIi4

Immune response elicited by two rBCG strains devoid of genes involved in c-di-GMP metabolism affect protection versus challenge with M. tuberculosis strains of different virulence

Publication date: Available online 15 March 2018
Source:Vaccine
Author(s): Cristian Alfredo Segura-Cerda, Michel de Jesús Aceves-Sánchez, Brenda Marquina-Castillo, Dulce Mata-Espinoza, Jorge Barrios-Payán, Perla Jazmín Vega-Domínguez, César Pedroza-Roldán, Jorge Bravo-Madrigal, Alba Adriana Vallejo-Cardona, Rogelio Hernández-Pando, Mario Alberto Flores-Valdez
Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles. We found that deletion of the BCG1419c (Delta c-di-GMP phosphodiesterase, ΔPDE) gene, or deletion of the BCG1416c (Delta c-di-GMP diguanylate cyclase, ΔDGC) gene, altered production of TNF-α, IL-6, and IL-1β, in murine macrophages, and resulted in attenuation in intra-macrophage replication. Moreover, in addition to the improved immunogenicity of the BCGΔBCG1419c mutant already reported, deletion of the BCG1416c gene leads to increased T CD4⁺ and T CD8⁺ activation. This correlated with protection versus lethality in mice infected with the highly virulent M. tuberculosis 5186 afforded by vaccination with all the tested BCG strains, and controlled the growth of the mildly virulent M. tuberculosis H37Rv in lungs by vaccination with BCGΔBCG1419c during chronic late infection from 4 to 6 months after challenge. Furthermore, when grown as surface pellicles, a condition used to manufacture BCG vaccine, in comparison to BCG wild type, both rBCGs changed expression of antigenic proteins such as DnaK, HbhA, PstS2, 35KDa antigen, GroEL2, as well as AcpM, a protein involved in synthesis of mycolic acids, molecules relevant to modulate inflammatory responses.

http://ift.tt/2FAVtBD

Impact of dynamical and microphysical schemes on black carbon prediction in a regional climate model over India

Abstract

Aerosol concentrations and their properties strongly depend on dynamics of atmosphere. Effects of physical and dynamical parameterizations on meteorology and black carbon (BC) mass in Weather Research and Forecasting model coupled with Chemistry (WRF-CHEM) are investigated over India. Simulations are performed in ten experiments considering two boundary layer, three cumulus parameterization, and five microphysics schemes during winter and monsoon of 2008. Morrison double-moment physical parameterization, Yonsei University boundary layer parameterization with Kain-Fritsch and Grell-Freitas cumulus parameterization schemes are found suitable to simulate meteorology and BC mass over India. BC mass is found to be underestimated in almost all experiments during winter; while, BC mass is overestimated in monsoon over Ahmedabad, Delhi, and Kanpur, which suggests inefficient wet scavenging of BC in monsoon, while lower emission rate may cause differences in winter. The results will be useful in understanding parameterizations and their impact on aerosols.

http://ift.tt/2pePFmx

How to choose among the multiple options to enhance the penetration of topically applied methyl aminolevulinate prior to photodynamic therapy

Publication date: June 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 22
Author(s): Valerio De Vita

http://ift.tt/2HApbU2

Effectiveness of adjunctive antimicrobial photodynamic therapy in reducing peri-implant inflammatory response in individuals vaping electronic cigarettes: A randomized controlled clinical trial

Publication date: Available online 15 March 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Mohammed Q. Al Rifaiy, Osama A. Qutub, Mohammed N. Alasqah, Zeyad H. Al-Sowygh, Sameer A. Mokeem, Ali Alrahlah
BackgroundThere are no studies that have assessed the effectiveness of antimicrobial photodynamic therapy (aPDT) in reducing peri-implant inflammatory response in individuals vaping electronic cigarettes (e-cigs). This study explored the effectiveness of aPDT as an adjunct to mechanical debridement (MD) in the treatment of peri-implant mucositis (p-iM) in individuals vaping e-cigs.MethodsVaping individuals with p-iM were divided into 2 groups: (a) Group-I: receiving MD with aPDT (test group); and (b) Group-II: MD only (control group). Peri-implant inflammatory parameters including plaque index (PI), bleeding on probing (BoP), and pocket depth (PD) were assessed at baseline and 12-weeks follow-up. Inter- and intra-group comparisons were made using Mann-Whitney U test and Wilcoxon signed ranks test. P-value < 0.05 was considered significant.ResultsThirty-eight male patients (20 in Group-I and 18 in Group-II) were included. The mean age of vaping individuals in groups I and II were 33.6 ± 2.8 and 35.4 ± 2.1 years, respectively. Mean daily frequency of vaping e-cigs in groups I and II was 7.3 ± 0.9 and 5.9 ± 1.0 whereas mean duration of vaping e-cigs was 4.8 ± 1.5 and 4.1 ± 1.3 years respectively. There was no significant difference between groups at baseline. There was significant improvement in PI (p < 0.001) and PD (p < 0.001) at 12-weeks follow-up with respect to the baseline visit in both groups. There was a significant reduction in PI (p < 0.001) and PD (p < 0.001) for group-I as compared to group-II at follow-up. There was no statistically significant difference for BoP between groups at follow-up.ConclusionAntimicrobial PDT is more effective compared to MD alone in the treatment of p-iM in individuals vaping e-cigs. The findings of the present study should be considered preliminary and interpreted with caution. Further randomized clinical trials should be performed in order to obtain strong conclusions.

http://ift.tt/2FWDZPy

A Single Radioactive Iodine Treatment Has a Deleterious Effect on Ovarian Reserve in Women with Thyroid Cancer: Results of a Prospective Pilot Study

Thyroid, Ahead of Print.

http://ift.tt/2peMTgY

Comment on: A Kidney Conundrum: More or Less?

Publication date: Available online 14 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Arjun Sahgal

http://ift.tt/2piMxGq

Predictors of Hypothyroidism in Hodgkin Lymphoma Survivors after Intensity-Modulated versus 3-Dimensional Radiation Therapy

Publication date: Available online 14 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Chelsea C. Pinnix, Laura Cella, Therese Y. Andraos, Zeina Ayoub, Sarah A. Milgrom, Jillian Gunther, Sonali Thosani, Christine Wogan, Manuel Conson, Vittoria D'Avino, Yasuhiro Oki, Michelle Fanale, Hun J. Lee, Sattva Neelapu, Luis Fayad, Frederick Hagemeister, M. Alma Rodriguez, Loretta J. Nastoupil, Yago Nieto, Wei Qiao, Roberto Pacelli, Bouthaina Dabaja
PurposeTo identify predictors of hypothyroidism after chemoradiation for Hodgkin lymphoma (HL) and to compare outcomes after intensity-modulated radiation therapy RT (IMRT) with those after 3-dimensional conformal RT (3D-CRT).Patients and MethodsNinety patients given involved-site IMRT in 2009–2014 were evaluated for treatment-induced hypothyroidism, defined as elevated thyroid-stimulating hormone (TSH) or decreased free thyroxine (fT4) levels or both. Receiver operating characteristic curve analysis identified individuals at low vs. high risk based on dosimetric variables. Dosimetric cutoff points were verified with an external dataset of 50 patients given 3D-CRT.ResultsMost patients given IMRT (75 [83%]) had stage II HL and the median prescribed dose was 30.6 Gy; in the 3D-CRT group 32 (64%) had stage II HL and the median prescribed dose was 32.0 Gy. No differences were found in proportions of patients with bilateral (P=0.982) or unilateral neck involvement (P=0.074) between either group. Hypothyroidism rates were marginally higher in the IMRT group, with estimated 3-year rates of freedom from hypothyroidism of 56.1% for the 3D-CRT group and 40% for the IMRT group (P=0.057). Univariate analysis showed that smaller thyroid volume and higher thyroid dose were associated with hypothyroidism in both groups (P<0.05). In the IMRT group, V25 and the absolute volume of thyroid spared from 25 Gy (VS25Gy) were the strongest predictors of hypothyroidism (P=0.001 and P<0.001). Cutoff points of 63.5% (V25) and 2.2 mL (VS25Gy) classified patients as high-risk (80%-82%) or low-risk (37%-44%) (P<0.001). Use of a thyroid avoidance structure reduced the incidence of hypothyroidism (P<0.05) in the IMRT group.ConclusionsThe percentage of thyroid receiving 25 Gy and the volume of thyroid spared from 25 Gy predicted risk of hypothyroidism after either IMRT or 3D-CRT for HL. IMRT may confer a higher risk than 3D-CRT unless a treatment avoidance structure is used during planning.

Teaser

In this comprehensive evaluation of risk factors associated with hypothyroidism after IMRT and involved-site RT for HL, identified variables included thyroid V25 and V30 and both absolute thyroid volume (cut point 11.2 mL) and volume spared from ≥25 Gy (≥2.2 mL). We further recommend contouring the thyroid and using thyroid avoidance structures in treatment planning when they do not compromise target coverage.

http://ift.tt/2Iqz73J

The Children’s Oncology Group Radiation Oncology Discipline: 15 Years of Contribution to the Treatment of Childhood Cancer

Publication date: Available online 14 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): John C. Breneman, Sarah S. Donaldson, Louis Constine, Thomas Merchant, Karen Marcus, Arnold Paulino, David Followill, Anita Mahajan, Nadia Laack, Natia Esiashvili, Daphne Haas-Kogan, Fran Laurie, Arthur Olch, Kenneth Ulin, David Hodgson, Torunn I. Yock, Stephanie Terezakis, Matt Krasin, Joseph Panoff, Paul Chuba, Chia-Ho Hua, Clayton B. Hess, Peter J. Houghton, Suzanne Wolden, Jeff Buchsbaum, Thomas J. Fitzgerald, John A. Kalapurakal
PurposeTo review the advances in radiation therapy for the management of pediatric cancers made by the Children's Oncology Group (COG) radiation oncology discipline since its inception in 2000.Methods and MaterialsThe various radiation oncology disease site leaders reviewed the contributions and advances in pediatric oncology made through the work of COG. They have presented outcomes of relevant studies and summarized current treatment policies developed by consensus from experts in the field.ResultsThe indications and techniques for pediatric radiation therapy have evolved considerably over the years for virtually all pediatric tumor types, resulting in improved cure rates together with the potential for decreased treatment-related morbidity and mortality.ConclusionsThe COG radiation oncology discipline has made significant contributions towards the treatment of childhood cancer. Our discipline is committed to continuing research to refine and modernize the use of radiation therapy in current and future protocols with the goal of further improving the cure rates and quality of life of children stricken with cancer.

http://ift.tt/2pdaBKE

Untangling Waist Circumference and Hip Circumference from Body Mass Index with a Body Shape Index, Hip Index, and Anthropometric Risk Indicator

Metabolic Syndrome and Related Disorders, Ahead of Print.

http://ift.tt/2GuwQnI

Sexual Coercion and Women's Education: A Pilot Study

Violence and Gender, Ahead of Print.

http://ift.tt/2GsxDFp

Addressing Onset and Desistance of Bullying Behavior: Surveying Perpetrators

Violence and Gender, Ahead of Print.

http://ift.tt/2tOXCEp

Anti-Podocalyxin Monoclonal Antibody 47-mG2a Detects Lung Cancers by Immunohistochemistry

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.

http://ift.tt/2pcoKZt

Open letter to journal editors on: international consensus radiochemistry nomenclature guidelines.

Open letter to journal editors on: international consensus radiochemistry nomenclature guidelines.

Am J Nucl Med Mol Imaging. 2018;8(1):70-72

Authors: Coenen HH, Gee AD, Adam M, Antoni G, Cutler CS, Fujibayashi Y, Jeong JM, Mach RH, Mindt TL, Pike VW, Windhorst AD

PMID: 29531863 [PubMed]

http://ift.tt/2tOMirT

Diagnostic performance of PET/MR in the evaluation of active inflammation in Crohn disease.

Diagnostic performance of PET/MR in the evaluation of active inflammation in Crohn disease.

Am J Nucl Med Mol Imaging. 2018;8(1):62-69

Authors: Catalano OA, Wu V, Mahmood U, Signore A, Vangel M, Soricelli A, Salvatore M, Gervais D, Rosen BR

Abstract
This study investigates the performance of PET/MR versus each sub-modality alone in the assessment of active inflammation in patients with Crohn disease, when compared to surgery as standard of reference. Sensitivity for detecting active inflammation was 91.5% for PET, 80% for MR, and 88% for PET/MR. Specificity for active inflammation was 74% for PET, 87% for MR, and 93% for PET/MR. Diagnostic accuracy was 84% for PET, 83% for MR, and 91% for PET/MR. In conclusion, PET/MR is significantly more accurate than either sub-modality alone and more specific than PET alone in the detection of active inflammation in patients with Crohn disease.

PMID: 29531862 [PubMed]

http://ift.tt/2FWeFcu

Thalamic and basal ganglia metabolism on interictal 18F-FDG PET in temporal lobe epilepsy: an SUV-based analysis.

Thalamic and basal ganglia metabolism on interictal 18F-FDG PET in temporal lobe epilepsy: an SUV-based analysis.

Am J Nucl Med Mol Imaging. 2018;8(1):41-49

Authors: Jain A, Struck AF, Woo KM, Jaskowiak CJ, Hall LT

Abstract
The aim of this study was to investigate thalamic and basal ganglia (BG) metabolism in temporal lobe epilepsy (TLE) on interictal 18F-FDG PET using standardized uptake value (SUV). Retrospective review of data was undertaken for patients who were surgically treated for medically intractable TLE. All patients underwent 18F-FDG PET, MRI brain and EEG as preoperative workup, and subsequently underwent temporal lobe resection. Postoperative outcomes were analyzed as without or with residual disabling seizures. SUVmax and SUVpeak values were calculated for thalamus and BG. Subgroup comparisons were performed with non-parametric tests. Study sample consisted of 33 patients (58% female; mean age 44.7 years) and 33 age- and sex-matched controls. Mean SUVpeak for both right and left thalamus was significantly lower in TLE than controls (8.1 ± 1.9 vs. 9.7 ± 2.9 and 8.1 ± 1.9 vs. 9.8 ± 2.9, respectively, both p=0.035). Mean SUVpeak for thalamus on the epileptogenic side was overall significantly lower than the contralateral side (8.0 ± 2.0 vs. 8.3 ± 2.0, p=0.040). One (3%) patient with MRI- and EEG-congruent left TLE showed marked left thalamic hypometabolism as the only finding on PET. There was no evidence of basal ganglia hypometabolism. No correlation was noted between thalamic metabolic asymmetry and postoperative outcomes. Thalamic metabolism was significantly reduced in patients with TLE compared to controls, and on the epileptogenic compared to the contralateral side among patients. Thalamic hypometabolism can have value in seizure focus localization in patients without interictal temporal hypometabolism.

PMID: 29531860 [PubMed]

http://ift.tt/2Hx9L2L

Synthesis, radiolabelling, and evaluation of [11C]PB212 as a radioligand for imaging sigma-1 receptors using PET.

Synthesis, radiolabelling, and evaluation of [11C]PB212 as a radioligand for imaging sigma-1 receptors using PET.

Am J Nucl Med Mol Imaging. 2018;8(1):32-40

Authors: Spinelli F, Haider A, Toscano A, Pati ML, Keller C, Berardi F, Colabufo NA, Abate C, Ametamey SM

Abstract
The Sigma-1 receptor (Sig-1R) has been described as a pluripotent modulator of distinct physiological functions and its involvement in various central and peripheral pathological disorders has been demonstrated. However, further investigations are required to understand the complex role of the Sig-1R as a molecular chaperon. A specific PET radioligand would provide a powerful tool in Sig-1R related studies. As part of our efforts to develop a Sig-1R PET radioligand that shows antagonistic properties, we investigated the suitability of 1-(4-(6-methoxynaphthalen-1-yl)butyl)-4-methylpiperidine (designated PB212) for imaging Sig-1R. PB212 is a Sig-1R antagonist and exhibits subnanomolar affinity (Ki = 0.030 nM) towards Sig-1R as well as good to excellent selectivity over Sig-2R. The radiolabelling of [11C]PB212 was accomplished by O-methylation of the phenolic precursor using [11C]MeI. In vitro autoradiography with [11C]PB212 on WT and Sig-1R KO mouse brain tissues revealed high non-specific binding, however using rat spleen tissues from CD1 mice and Wistar rats, high specific binding was observed. The spleen is known to have a high expression of Sig-1R. In vivo PET experiments in Wistar rats also showed high accumulation of [11C]PB212 in the spleen. Injection of Sig-1R binding compounds, haloperidol (1 mg/kg) or fluspidine (1 mg/kg) shortly before [11C]PB212 administration induced a drastic reduction of radiotracer accumulation, confirming the specificity of [11C]PB212 towards Sig-1R in the spleen. The results obtained herein indicate that although [11C]PB212 is not suitable for imaging Sig-1R in the brain, it is a promising candidate for the detection and quantification of Sig-1Rs in the periphery.

PMID: 29531859 [PubMed]

http://ift.tt/2GuqJj8

Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

Am J Nucl Med Mol Imaging. 2018;8(1):15-31

Authors: Velikyan I, Lindhe Ö

Abstract
Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to αvβ3 integrin receptors. The main objective of this study was to develop a method for 68Ga-labeling of RGD containing bicyclic octapeptide ([68Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [68Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [68Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis.

PMID: 29531858 [PubMed]

http://ift.tt/2tT0pMK

Adenoid cystic carcinoma: focus on heavy ion therapy and molecular imaging.

Adenoid cystic carcinoma: focus on heavy ion therapy and molecular imaging.

Am J Nucl Med Mol Imaging. 2018;8(1):1-14

Authors: Castello A, Olivari L, Lopci E

Abstract
Surgery, radiation therapy and chemotherapy are the oldest modalities for cancer treatment. However, as part of a continuous research in medicine, in order to improve therapeutic precision and biological effectiveness, there is an increasing interest into the use of heavy particle (e.g. protons or heavy ions) in the treatment of solid tumors. However, the restricted availability of the technology has concentrated the expertise in highly specialized centers that take care and treat extreme cases and rare pathologies. One of the tumors that has mostly beneficiated from heavy ion therapy is represented by adenoid cystic carcinoma (ACC) of the head and neck. In the current review we will focus our attention on the role of heavy particle therapy in general, with particular interest on ACC. The article will also summarize recent clinical evidence comparing traditional radiotherapy with the new heavy particles. Moreover, molecular imaging features of this uncommon tumor with 18F-FDG and 11C-MET will be discussed and illustrated.

PMID: 29531857 [PubMed]

http://ift.tt/2FTNzmp

Plasticity of myeloid-derived suppressor cells in cancer

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Evgenii Tcyganov, Jerome Mastio, Eric Chen, Dmitry I Gabrilovich
In recent years, myeloid-derived suppressor cells (MDSC) have emerged as one of the major inhibitors of immune effector cell function in cancer. MDSC represent a heterogeneous population of largely immature myeloid cells that are characterized by a pathological state of activation and display potent immune suppressive activity. Two major subsets of MDSC have been identified: monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC). PMN-MSDC share phenotypic and morphologic features with neutrophils, whereas M-MDSC are similar to monocytes and are characterized by high plasticity. Differentiation of M-MDSC to macrophages and dendritic cells is shaped by tumor microenvironment. In recent years, the mechanisms of this process start to emerge.

http://ift.tt/2piGKka

Editors, Issue sections

Publication date: February 2018
Source:Current Opinion in Immunology, Volume 50

http://ift.tt/2ItysOX

Contents, Cover details

Publication date: February 2018
Source:Current Opinion in Immunology, Volume 50

http://ift.tt/2piGzp0

Consolidative mechanisms of emotional processing in REM sleep and PTSD

Research suggests sleep plays a role in the consolidation of recently acquired memories for long-term storage. Rapid eye movement (REM) sleep has been shown to play a complex role in emotional-memory processing, and may be involved in subsequent waking-day emotional reactivity and amygdala responsivity. Interaction of the hippocampus and basolateral amygdala with the medial-prefrontal cortex is associated with sleep-dependent learning and emotional memory processing. REM is also implicated in post-traumatic stress disorder (PTSD), which is characterized by sleep disturbance, heightened reactivity to fearful stimuli, and nightmares.

http://ift.tt/2GtEEWL

A dataset of small molecules triggering transcriptional and translational cellular responses

Publication date: April 2018
Source:Data in Brief, Volume 17
Author(s): Mathilde Koch, Amir Pandi, Baudoin Delépine, Jean-Loup Faulon
The aim of this dataset is to identify and collect compounds that are known for being detectable by a living cell, through the action of a genetically encoded biosensor and is centred on bacterial transcription factors. Such a dataset should open the possibility to consider a wide range of applications in synthetic biology. The reader will find in this dataset the name of the compounds, their InChI (molecular structure), the publication where the detection was reported, the organism in which this was detected or engineered, the type of detection and experiment that was performed as well as the name of the biosensor. A comment field is also provided that explains why the compound was included in the dataset, based on quotes from the reference publication or the database it was extracted from. Manual curation of ACS Synthetic Biology abstracts (Volumes 1 to 6 and Volume 7 issue 1) was performed as well as extraction from the following databases: Bionemo v6.0 (Carbajosa et al., 2009) [1], RegTransbase r20120406 (Cipriano et al., 2013) [2], RegulonDB v9.0 (Gama-Castro et al., 2016) [3], RegPrecise v4.0 (Novichkov et al., 2013) [4] and Sigmol v20180122 (Rajput et al., 2016) [5].

http://ift.tt/2DsHLLn

Fluorescence microscopy data on expression of Paired Box Transcription Factor 7 in skeletal muscle of APOBEC2 knockout mice

Publication date: April 2018
Source:Data in Brief, Volume 17
Author(s): Hideaki Ohtsubo, Yusuke Sato, Yuji Matsuyoshi, Takahiro Suzuki, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi
The data presented in this article are related to the research articles entitled "APOBEC2 negatively regulates myoblast differentiation in muscle regeneration" and "Data supporting possible implication of APOBEC2 in self-renewal functions of myogenic stem satellite cells: toward understanding the negative regulation of myoblast differentiation" (Ohtsubo et al., 2017a, 2017b) [1,2]. This article provides in vivo phenotypical data to show that Paired Box Transcription Factor 7 (Pax7)-positive cell number (per myofiber) is significantly lower in APOBEC2 (a member of apoB mRNA editing enzyme, catalytic polypeptide-like family)-knockout muscle than the control wild-type tissue at the same age of 8-wk-old in mice. The emerging results support an essential role for APOBEC2 in the self-renewal functions of myogenic stem satellite cells, namely the re-establishment of quiescent status after activation and proliferation of myoblasts.

http://ift.tt/2GtFq5Q

Myeloid derived-suppressor cells: their role in cancer and obesity

Suzanne Ostrand-Rosenberg

http://ift.tt/2FC1xKj

The Implementation and First‐Round Results of a Community‐Based Colorectal Cancer Screening Program in Shanghai, China

AbstractBackground.The incidence and mortality rate of colorectal cancer (CRC) have increased dramatically over the past 3 decades in China due to changes in lifestyle factors. Early detection and treatment guidelines for asymptomatic cases have shown to improve CRC control in developed countries. In response to these challenges, the Shanghai Municipal Government launched a community‐based CRC screening program in 2012.Materials and Methods.Free initial screening, inclusive of immunochemical fecal occult blood and risk assessment (questionnaire), was provided by community health centers in Shanghai. Participants with positive results were referred to a specialist for a colonoscopy.Results.In 2013, 828,302 Shanghai residents were registered; 97.7% (809,528) of the registrants completed initial screening. Among 180,094 initial screening‐positive participants, 71,733 underwent colonoscopy. The proportion of compliance to colonoscopy was 39.8%; the proportion decreased with age and educational level. A total of 6,668 adenomas were detected, and 1,630 CRC cases were diagnosed. The CRC detection rate of the program was 201.35/100,000; among the detected CRCs, 51.6% were in stage 0–I.Conclusion.The screening program achieved great progress, especially on initial screening completion and CRC early stage rate, although particular intervention is still needed to improve the compliance of colonoscopy.Implications for Practice.Due to socioeconomic transitions and lifestyle changes, colorectal cancer is now becoming one of the most common cancers in developing countries, as it is in developed countries. While most developed countries have now initiated national colorectal cancer screening programs based on recommended country‐specific colorectal cancer screening guidelines, colonoscopy has become the most commonly used screening method. This is a challenge in developing countries due to limited resources. Based on the analysis of the Shanghai colorectal cancer screening program, with immunological fecal occult blood test and risk assessment as initial screening, followed by a diagnostic testing of colonoscopy for individuals with positive results, this article provides the basis and suggestion for similar program in other regions of China and other developing countries.

http://ift.tt/2FQXFEF

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck

AbstractLessons Learned. Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective.Background.The objective of this study was to establish the response rate, progression‐free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN).Materials and Methods.Twenty‐nine patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status <3 were enrolled in an institutional review board‐approved phase II trial. This study permitted prior chemoradiation, radiation, and/or surgery, provided that 3 months had elapsed since the end of the potentially curative treatment. Patients received cisplatin 30 mg/m2 or carboplatin area under the curve (AUC) 2, docetaxel 30 mg/m2, and cetuximab 250 mg/m2 weekly for 3 weeks, followed by a break during the fourth week, for a 28‐day cycle. Planned intrapatient dose modifications were based on individual toxicity.Results.Twenty‐seven patients received TPC and were evaluable for response and toxicity. Rates of complete response (CR), partial response (PR), and confirmed PR were 3%, 52%, and 30%, respectively. The overall objective response rate was 56%. Estimated median PFS and OS were 4.8 and 14.7 months, respectively. The rates of grade 3 and 4 worst‐grade adverse events (AEs) per patient were 85% and 7%, respectively. Dose density through cycle 4 was preserved for all patients; however, treatment beyond cycle 6 with the TPC regimen proved unfeasible.Conclusion.Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments. Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens using less frequent, higher‐dose chemotherapy schedules.

http://ift.tt/2tR54yQ

Hybrid Capture‐Based Comprehensive Genomic Profiling Identifies Lung Cancer Patients with Well‐Characterized Sensitizing Epidermal Growth Factor Receptor Point Mutations That Were Not Detected by Standard of Care Testing

AbstractBackground.In our recent study, of cases positive for epidermal growth factor receptor (EGFR) exon 19 deletions using comprehensive genomic profiling (CGP), 17/77 (22%) patients with prior standard of care (SOC) EGFR testing results available were previously negative for exon 19 deletion. Our aim was to compare the detection rates of CGP versus SOC testing for well‐characterized sensitizing EGFR point mutations (pm) in our 6,832‐patient cohort.Materials and Methods.DNA was extracted from 40 microns of formalin‐fixed paraffin‐embedded sections from 6,832 consecutive cases of non‐small cell lung cancer (NSCLC) of various histologies (2012–2015). CGP was performed using a hybrid capture, adaptor ligation‐based next‐generation sequencing assay to a mean coverage depth of 576×. Genomic alterations (pm, small indels, copy number changes and rearrangements) involving EGFR were recorded for each case and compared with prior testing results if available.Results.Overall, there were 482 instances of EGFR exon 21 L858R (359) and L861Q (20), exon 18 G719X (73) and exon 20 S768I (30) pm, of which 103 unique cases had prior EGFR testing results that were available for review. Of these 103 cases, CGP identified 22 patients (21%) with sensitizing EGFR pm that were not detected by SOC testing, including 9/75 (12%) patients with L858R, 4/7 (57%) patients with L861Q, 8/20 (40%) patients with G719X, and 4/7 (57%) patients with S768I pm (some patients had multiple EGFR pm). In cases with available clinical data, benefit from small molecule inhibitor therapy was observed.Conclusion.CGP, even when applied to low tumor purity clinical‐grade specimens, can detect well‐known EGFR pm in NSCLC patients that would otherwise not be detected by SOC testing. Taken together with EGFR exon 19 deletions, over 20% of patients who are positive for EGFR‐activating mutations using CGP are previously negative by SOC EGFR mutation testing, suggesting that thousands of such patients per year in the U.S. alone could experience improved clinical outcomes when hybrid capture‐based CGP is used to inform therapeutic decisions.Implications for Practice.This study points out that genomic profiling, as based on hybrid capture next‐generation sequencing, can identify lung cancer patients with point mutation in epidermal growth factor receptor (EGFR) missed by standard molecular testing who can likely benefit from anti‐EGFR targeted therapy. Beyond the specific findings regarding false‐negative point mutation testing for EGFR, this study highlights the need for oncologists and pathologists to be cognizant of the performance characteristics of testing deployed and the importance of clinical intuition in questioning the results of laboratory testing.

http://ift.tt/2FU8Tbe

Diagnostic performance of PET/MR in the evaluation of active inflammation in Crohn disease.

Diagnostic performance of PET/MR in the evaluation of active inflammation in Crohn disease.

Am J Nucl Med Mol Imaging. 2018;8(1):62-69

Authors: Catalano OA, Wu V, Mahmood U, Signore A, Vangel M, Soricelli A, Salvatore M, Gervais D, Rosen BR

PMID: 29531862 [PubMed]

http://ift.tt/2FWeFcu

Thalamic and basal ganglia metabolism on interictal 18F-FDG PET in temporal lobe epilepsy: an SUV-based analysis.

Thalamic and basal ganglia metabolism on interictal 18F-FDG PET in temporal lobe epilepsy: an SUV-based analysis.

Am J Nucl Med Mol Imaging. 2018;8(1):41-49

Authors: Jain A, Struck AF, Woo KM, Jaskowiak CJ, Hall LT

PMID: 29531860 [PubMed]

http://ift.tt/2Hx9L2L

Synthesis, radiolabelling, and evaluation of [11C]PB212 as a radioligand for imaging sigma-1 receptors using PET.

Synthesis, radiolabelling, and evaluation of [11C]PB212 as a radioligand for imaging sigma-1 receptors using PET.

Am J Nucl Med Mol Imaging. 2018;8(1):32-40

Authors: Spinelli F, Haider A, Toscano A, Pati ML, Keller C, Berardi F, Colabufo NA, Abate C, Ametamey SM

PMID: 29531859 [PubMed]

http://ift.tt/2GuqJj8

Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

Am J Nucl Med Mol Imaging. 2018;8(1):15-31

Authors: Velikyan I, Lindhe Ö

PMID: 29531858 [PubMed]

http://ift.tt/2tT0pMK

Adenoid cystic carcinoma: focus on heavy ion therapy and molecular imaging.

Adenoid cystic carcinoma: focus on heavy ion therapy and molecular imaging.

Am J Nucl Med Mol Imaging. 2018;8(1):1-14

Authors: Castello A, Olivari L, Lopci E

PMID: 29531857 [PubMed]

http://ift.tt/2FTNzmp

Mutation detection using plasma circulating tumor DNA (ctDNA) in a cohort of asymptomatic adults at increased risk for cancer.

Mutation detection using plasma circulating tumor DNA (ctDNA) in a cohort of asymptomatic adults at increased risk for cancer.

Int J Mol Epidemiol Genet. 2018;9(1):1-12

Authors: Kammesheidt A, Tonozzi TR, Lim SW, Braunstein GD

Abstract
PURPOSE: The primary purpose of this study was to clinically evaluate circulating tumor DNA (ctDNA) with a nine gene, 96 mutation panel among subjects at increased risk for cancer with no previous cancer diagnosis.
SUBJECTS AND METHODS: DNA from 1059 asymptomatic subjects was analyzed for detection of low levels ctDNA using a blood plasma liquid biopsy assay. Subjects with detectable copies of ctDNA were asked to provide additional blood samples and relevant medical records throughout their one-year of participation. Subjects with a negative result were followed-up at one-year with a questionnaire.
RESULTS: Mutations were detected in 58 subjects and not detected in 1001 subjects. Among the subjects who tested positive for one or more mutations, four were diagnosed with cancer, two of which through study-triggered clinical follow-up. Two subjects who tested negative on the screen received an early cancer diagnosis over the course of the year. The sensitivity of the assay at a threshold of ≥2 copies in this population was 66.67% and specificity was 94.87%. While the negative predictive value was 99.8%, the positive predictive value was only 6.9% in this cohort. Analysis of buffy coat DNA from eight positive subjects, including one who was diagnosed with cancer, revealed matching mutations suggesting that the ctDNA could have been derived from clonal hematopoiesis.
CONCLUSION: The observed false positive rate of ctDNA on a 96-mutation assay in an asymptomatic high-risk population is much greater than the true positive rate, limiting its usefulness as a cancer screening tool in its current form.

PMID: 29531639 [PubMed]

http://ift.tt/2paFikm

Mucoepidermoid carcinoma of the parotid gland: A National Cancer Database study

To describe the demographics, tumor characteristics, and prognostic features of mucoepidermoid carcinoma of the parotid gland.

http://ift.tt/2FzLe0F

Are surgeons overdosing patients with lidocaine?

Local anesthetics have long been used since the 1850s following the first pure extraction of cocaine from coca leaves. Cocaine was a potent anesthetic, however, it led to deaths and addictions for health care members and patients alike [1]. Other local anesthetics such as tetracaine, tropocaine, lidocaine, bupivacaine and more recently, ropivacaine, were synthesized to minimize the cocaine toxicity. These newer anesthetic agents included both ester and amide preparationswith varying degrees of cardiovascular and neurotoxicity [1].

http://ift.tt/2HAxi2T

High NOTCH1 mRNA Expression Is Associated with Better Survival in HNSCC.

High NOTCH1 mRNA Expression Is Associated with Better Survival in HNSCC.

Int J Mol Sci. 2018 Mar 13;19(3):

Authors: Wirth M, Jira D, Ott A, Piontek G, Pickhard A

Abstract
The clinical impact of the expression of NOTCH1 signaling components in squamous cell carcinoma of the pharynx and larynx has only been evaluated in subgroups. The aim of this study was therefore to evaluate NOTCH1 expression in head and neck squamous cell cancer (HNSCC) patient tissue and cell lines. We analyzed tissue from 195 HNSCCs and tissue from 30 normal patients for mRNA expression of NOTCH1, NOTCH3, HES1, HEY1, and JAG1 using quantitative real-time PCR. Association of expression results and clinical orpathological factors was examined with multivariate Cox regression. NOTCH1 expression was determined in three Human Papilloma Virus (HPV)-positive and nine HPV-negative HNSCC cell lines. High expression of NOTCH1 was associated with better overall survival (p = 0.013) and disease-free survival (p = 0.040). Multivariate Cox regression confirmed the significant influence of NOTCH1 expression on overall survival (p = 0.033) and disease-free survival (p = 0.029). A significant correlation was found between p16 staining and NOTCH1 mRNA expression (correlation coefficient 0.28; p = 0.01). NOTCH1 was expressed at higher levels in HPV-positive HNSCC cell lines compared with HPV-negative cell lines, which was not statistically significant (p = 0.068). We conclude that NOTCH1 expression is associated with overall survival, and that inhibition of NOTCH1 therefore seems less promising.

PMID: 29533972 [PubMed - in process]

http://ift.tt/2FHHy8U

Recent progress on the photocatalysis of carbon dots: Classification, mechanism and applications

Publication date: Available online 12 March 2018
Source:Nano Today
Author(s): Mei Han, Shoujun Zhu, Siyu Lu, Yubin Song, Tanglue Feng, Songyuan Tao, Junjun Liu, Bai Yang
With the rapid development of science and technology, environmental pollution and energy shortage become more and more prominent. To solve these problems, photocatalytic technology is regarded as one of the most efficient methods, allowing for both pollutant degradation and energy conversion. Compared with traditional group IIVI, IIIV quantum dots (QDs), carbon dots (CDs), as a newly emerging kind of fluorescent carbon-based material, possess many excellent properties, such as high aqueous solubility, low cost, low toxicity, abundant surface functional groups and good biocompatibility. In particular, the unique up-converted photoluminescence (PL) behavior and photo-induced electron transfer ability of CDs provide the new route to achieve efficient metal-free photocatalysts. This article reviews recent progress on CDs utilized for photocatalysis from different perspectives, including the following three parts: classification and synthesis, mechanism of CDs-derived photocatalysts as well as the applications for environmental issues (up-converted PL process) and energy conversion (photo-induced electron transfer process).

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http://ift.tt/2pezipW

Recent advances in functional nanomaterials for light–triggered cancer therapy

Publication date: Available online 13 March 2018
Source:Nano Today
Author(s): Shili Gai, Guixin Yang, Piaoping Yang, Fei He, Jun Lin, Dayong Jin, Bengang Xing
Photo–triggered therapeutic modalities for cancer have attracted enormous attention in recent years due to the easily focused and tuned properties of irradiation light that enable the localized treatment with non–invasive, direct and accurate characteristics. In addition, by using new developed functional nanomaterials, different therapeutic modalities can be integrated into a single platform, and co–therapies with dramatically enhanced anti–cancer ability by synergetic therapeutic effects are obtained. In the view of the fast development of anti–cancer strategy, we present an in–depth review of major breakthroughs in recent advanced functional nanomaterials for photo–triggered therapy. This review first summarizes the organic and inorganic photosensitizers for photodynamic therapy (PDT), four kinds of photothermal materials for photothermal therapy (PTT), as well as photo–switchable molecules or photolabile chemical groups bonded materials for chemotherapy. For each part, the therapeutic materials, mechanisms, superiorities and typical representatives are examined extensively. Then, we systematically discuss the optimized multifunctional nanomaterials consist of the above materials for PTT/PDT co–therapy, PTT/chemo co–therapy, PDT/chemo co–therapy and radiotherapy–composed co–therapy etc. And the synergetic therapeutic mechanism, anti–cancer efficiency, safety and design of therapeutic materials are highlighted. Finally, we give an outlook of the future directions of the rapidly growing functional nanomaterials for photo–triggered therapy, and propose several associated challenges and potential solutions.

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http://ift.tt/2In0BqR

Evolving Linear Chromosomes and Telomeres: A C-Strand-Centric View

Publication date: Available online 14 March 2018
Source:Trends in Biochemical Sciences
Author(s): Neal F. Lue
Recent studies have resulted in deeper understanding of a variety of telomere maintenance mechanisms as well as plausible models of telomere evolution. Often overlooked in the discussion of telomere regulation and evolution is the synthesis of the DNA strand that bears the 5′-end (i.e., the C-strand). Herein, I describe a scenario for telomere evolution that more explicitly accounts for the evolution of the C-strand synthesis machinery. In this model, CTC1-STN1-TEN1 (CST), the G-strand-binding complex that regulates primase-Pol α-mediated C-strand synthesis, emerges as a pivotal player and evolutionary link. Itself arising from RPA, CST not only coordinates telomere synthesis, but also gives rise to the POT1-TPP1 complex, which became part of shelterin and regulates telomerase in G-strand elongation.

http://ift.tt/2peJf6Y

Affimer Proteins: Theranostics of the Future?

Publication date: Available online 14 March 2018
Source:Trends in Biochemical Sciences
Author(s): Stuart Kyle
Affimer proteins can bind to a wide variety of target molecules. They can complement and represent a promising alternative to conventional antibodies as they can target molecules with high affinity, specificity, and stability. In addition, they can be selected and expressed in bacterial and mammalian systems. Affimer protein technology shows promise as a tool in the biologist's arsenal of the future in imaging, diagnostic, and therapeutic applications.

http://ift.tt/2IovwD8

Enacted stigma and felt stigma experienced by adults who stutter

Publication date: Available online 13 March 2018
Source:Journal of Communication Disorders
Author(s): Michael P. Boyle
PurposeThe aim of this study was to (1) document the experiences of enacted stigma (external stigma, experienced discrimination) and felt stigma (anticipation and expectation of discrimination or negative treatment by others) in adults who stutter, (2) investigate their relationships to each other, and (3) investigate their relationships to global mental health.MethodParticipants were 324 adults who stutter recruited from clinicians and self-help group leaders in the United States. Participants completed an anonymous web survey consisting of measures of enacted stigma, felt stigma, and global mental health. Data analysis focused on obtaining descriptive statistics for enacted stigma and felt stigma, and performing correlational analysis between these variables, and also between these variables and global mental health.ResultsMost participants reported experiencing several different forms of social devaluation and negative treatment from other people at some point in their lives (i.e., enacted stigma), although they rarely experienced these events during the past year. Most participants agreed that they anticipate future stigmatizing experiences (i.e., felt stigma). Enacted stigma in the past year demonstrated a significant positive relationship to felt stigma. Both enacted stigma in the past year and felt stigma demonstrated significant negative relationships with global mental health. Enacted stigma in the past year and felt stigma were unique predictors of participants' global mental health.ConclusionsPeople who stutter experience discrimination and social devaluation, and they anticipate future stigmatizing experiences. Both of these types of stigma, enacted and felt, are associated with reduced mental health. Assessment and therapy with adults who stutter should address these aspects of stuttering.

http://ift.tt/2DrZv9J

Beliefs and Behavioural Intentions Towards Pharmacotherapy for Stuttering: A Survey of Adults Who Stutter

Publication date: Available online 13 March 2018
Source:Journal of Communication Disorders
Author(s): Allan McGroarty, Rebecca McCartan
PurposeAlthough considerable efforts have been made to investigate the effectiveness of pharmacological treatments for stuttering, little is known about how the stuttering community perceives these treatments. This study aimed to assess and quantify beliefs regarding pharmacotherapy for adults who stutter and to establish whether behavioural intentions to undertake treatment were related to these beliefs.MethodAn adapted version of the Beliefs about Medicine Questionnaire was completed by adults who stutter. Participants also reported perceptions of their stuttering including its overall impact, ratings of previous speech therapy, and behavioural intentions to initiate pharmacotherapy and speech therapy in future.ResultsNecessity and concern beliefs were distributed widely across the sample and in a pattern indicating a relatively balanced perception of the benefits and costs of medication prescribed specifically for stuttering. Of the study's measures, the necessity-concerns differential most strongly predicted the behavioural intention to initiate pharmacotherapy. The overall impact of stuttering predicted intentions to seek both pharmacotherapy and speech therapy. Participants reported the likelihood of pursuing pharmacotherapy and speech therapy in equal measure.ConclusionsThe theoretical model of medication representations appears to be a useful framework for understanding the beliefs of adults who stutter towards the medical treatment of their disorder. The findings of this study may be of interest to clinicians and researchers working in the field of stuttering treatment and to people who stutter considering pharmacotherapy.

http://ift.tt/2FWpaN1

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! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 14 Μαρτίου 2018

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