Abdominal CT scan showed a well-delineated, low-density area that exhibited heterogeneous contrast enhancement. The area measured about 20 mm in size and was to the left of the aorta at the level of the inferior mesenteric artery. MRI showed a mass with heterogeneous hypointensity on T1-weighted images and heterogeneous hyperintensity on T2-weighted images. PET-CT scan showed slightly increased 18F-fluorodeoxyglucose accumulation within the mass. : Retroperitoneal ectopic thyroid tissue

Retroperitoneal ectopic thyroid tissue

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

6948891480

alsfakia@gmail.com

Mechanical characterization of curly hair: Influence of the use of nonconventional hair straightening treatments

Background/purpose

Hair straighteners are very popular around the world, although they can cause great damage to the hair. Thus, the characterization of the mechanical properties of curly hair using advanced techniques is very important to clarify how hair straighteners act on hair fibers and to contribute to the development of effective products. On this basis, we chose two nonconventional hair straighteners (formaldehyde and glyoxylic acid) to investigate how hair straightening treatments affect the mechanical properties of curly hair.

Methods

The mechanical properties of curly hair were evaluated using a tensile test, differential scanning calorimetry (DSC) measurements, scanning electronic microscopy (SEM), a torsion modulus, dynamic vapor sorption (DVS), and Fourier transform infrared spectroscopy (FTIR) analysis.

Results

The techniques used effectively helped the understanding of the influence of nonconventional hair straighteners on hair properties. For the break stress and the break extension tests, formaldehyde showed a marked decrease in these parameters, with great hair damage. Glyoxylic acid had a slight effect compared to formaldehyde treatment. Both treatments showed an increase in shear modulus, a decrease in water sorption and damage to the hair surface.

Conclusions

A combination of the techniques used in this study permitted a better understanding of nonconventional hair straightener treatments and also supported the choice of the better treatment, considering a good relationship between efficacy and safety. Thus, it is very important to determine the properties of hair for the development of cosmetics used to improve the beauty of curly hair.

http://ift.tt/2nQwk9x

Residual stresses induced by laser welding process in the case of a dual-phase steel DP600: Simulation and experimental approaches

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): A. Kouadri-Henni, C. Seang, B. Malard, V. Klosek
This study aimed at characterizing the residual stresses distribution of a DP600 undergoing a laser beam welding. The residual stresses in the ferritic phase have been experimentally determined by the use of the neutron diffraction technique. The results confirmed a gradient of residual stresses among different zones both on the top and below surfaces but also through the thickness of the fusion zone. Low compressive stresses were observed in the BM (Base metal) close to the HAZ zone (heat affected zone) whereas high tensile stresses were observed in the FZ (fusion zone). Two numerical modelling strategies were conducted: first with elastic plastic model (EP) and then with a visco-elastic plastic model (VEP) which takes into account the effect of phase transformation-induced volumetric strain. Both models allowed highlighting the residual stresses evolution through the different zones. Numerical results showed a difference in the residual stresses distribution depending on the model used. In the end, it appears that the high temperature, specific to the laser beam, is the main factor governing the residual stresses. When comparing simulation results with experimental data, the values converge well in some zones, in particular the FZ and the others less.

Graphical abstract

http://ift.tt/2mT2wIJ

A method to control delaminations in composites for adjusted energy dissipation characteristics

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): M. Kuhtz, A. Hornig, M. Gude, H. Jäger
Concepts to adjust the delamination behaviour of textile reinforced composites are investigated. The composite interfaces are modified by adjusting the interlaminar contact area using perforated PTFE-foils. According mode I and mode II energy release rates are determined and a progressive correlation between the interlaminar contact area and energy release rates is identified. The results are exploited within three point bending experiments to adapt the structural delamination and subsequent energy dissipation behaviour with the proposed interface modification concept. Two structural designs concepts are evaluated numerically: adjusting structural energy dissipation capacity and adjusting the peak levels as well as the characteristic trends of the structural reactive forces. It is demonstrated, that the mechanical response of composite structures can be tailored by controlling their delamination behaviour.

Graphical abstract

http://ift.tt/2mTamlt

Viscous flow and viscosity measurement of low-temperature imprintable AuCuSi thin film metallic glasses investigated by nanoindentation creep

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Cheng Wang, Yi-Chia Liao, Jinn P. Chu, Chun-Hway Hsueh
The viscous flow typically plays an important role for the deformation of metallic glasses in the supercooled liquid region. This deformation behavior has been widely investigated for bulk metallic glasses. However, studies on the viscous flow and viscosity measurement of thin film metallic glasses (TFMGs) were sparse. In this work, we synthesized four compositions of fully amorphous AuCuSi TFMGs by magnetron sputtering. The glass transition temperature, which is also the temperature of the critical transition point from elastic/plastic deformation to time-dependent viscous flow, was determined using nanoindentation. The nanoindentation creep tests performed with hemispherical and Berkovich indenter tips in the temperature range of 50 to 170°C were proven to be suitable for the viscosity measurements of AuCuSi TFMGs. The activation energy of the flow process was also evaluated from the indentation results and good agreement was obtained between the results evaluated from hemispherical and Berkovich tips. Finally, a nano-scaled imprinted AuCuSi TFMG showed great topological resolution.

Graphical abstract

http://ift.tt/2mSWiIS

Deposition of nanodiopside coatings on metallic biomaterials to stimulate apatite-forming ability

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Erfan Salahinejad, Reza Vahedifard
One of the drawbacks of metals and alloys in biomedical applications is their inefficient fixation to adjacent tissues which can be fairly addressed by applying bioactive ceramic coatings. In this work, colloidal suspensions based on coprecipitation-derived nanoparticulate diopside (CaMgSi2O6) were deposited on stainless steel 316L by dip-coating and subsequent low-temperature sintering. Afterwards, the structure, bioactivity and biodegradation of the samples were in vitro evaluated by spectroscopic and microscopic techniques. The apatite-forming ability of the surface was found to be improved by using the nanodiopside coating, while controlled by a typical ion-exchange reaction mechanism originating from the film's degradability. In this regard, after soaking the coated samples in a simulated body fluid, an integrated leaf-like precipitation of apatite at early stages and a following non-uniform rose-like growth of apatite with an increased level of the carbonate substitution for hydroxyl were detected. It is eventually concluded that nanodiopside coatings deserve further consideration and development in the biomedical field, where a bioactive fixation is needed along the implant/tissue interface.

Graphical abstract

http://ift.tt/2mSZu7b

Hierarchical porous Bi24O31Br10 microarchitectures assembled by ultrathin nanosheets with strong adsorption and excellent photocatalytic performances

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Jian Song, Lei Zhang, Jian Yang, Xin-Hua Huang, Jin-Song Hu
Construction of hierarchical structure assembled by ultrathin nanosheet is one of the important challenges in material chemistry and photocatalytic field, because this kind of material can combine the advantages of hierarchical structure and ultrathin material. Herein, we propose an ion-exchange approach to the fabrication of novel hierarchical porous Bi24O31Br10 microstructures assembled by ultrathin nanosheets with thicknesses of 3–5nm through a facile reflux process, employing previously-prepared Bi25VO40 micro-cubes as precursors of Bi³⁺ ions. Experiments revealed that the Bi24O31Br10 hierarchical structures possessed a high surface area (~67.16m²/g) and abundant mesopores, leading to the strong adsorption capacity for rhodamine B (RhB) with high concentration. The maximal adsorption quantity of the product was calculated to be 24.4mg/g. Photocatalytic results demonstrated that the as-prepared Bi24O31Br10 sample exhibited a significant structure-induced enhancement of photocatalytic performance. After 12min of UV–visible-light irradiation, 96% of RhB solution (40mg/L) could be completely decomposed. In addition, the trapping experiments confirmed that photo-generated hole was believed as the chief active specie in the degradation process of RhB molecule.Novelty statementConstruction of hierarchical structure assembled by ultrathin nanosheet is one of the important challenges in material chemistry, because this kind material can combine the advantages of hierarchical structure and ultrathin material. Unfortunately, controllable fabrication about hierarchical porous Bi24O31Br10 microstructures is still a huge challenge until today. Therefore, we afford a facile ion-exchange approach to the fabrication of novel hierarchical porous Bi24O31Br10 microstructures built up by ultrathin nanosheets. Moreover, benefiting from the unique hierarchical and ultrathin structural features, the as-obtained Bi24O31Br10 hierarchical structures exhibited strong adsorption abilities towards RhB with high concentration, as well as superior photocatalytic performance.

Graphical abstract

http://ift.tt/2mT0W9J

Facial Analysis to Classify Difficult Intubation

Condition:   Difficult Intubation
Intervention:   Other: photographing head and neck
Sponsor:   Wake Forest University Health Sciences
Recruiting - verified March 2017

http://ift.tt/2nQA7DP

Combined photographic and ultrasonographic measurement of the ANB angle: a pilot study

Abstract

Objective

This study was performed to evaluate the feasibility of noninvasive measurement of the ANB angle using photographic and ultrasonographic methods.

Methods

Twenty consecutive orthodontic patients were evaluated. The ANB angle and soft tissue thickness covering the N, A, and B cephalometric points were measured by lateral teleradiography; these measurements were made by two expert operators. The soft tissue thickness covering the N, A, and B cephalometric points was measured by ultrasonography; these measurements were also made by two expert operators. On a 1:1 photographic profile print on which the ultrasonographic points were marked, the ANB ultrasonographic angle was measured. The following comparisons were considered: averaged and single measurements of N, A, and B points by first versus second ultrasonographer; averaged and single ultrasonographic versus radiographic soft tissue thickness covering the N, A, B points; and averaged and single ultrasonographic versus radiographic measurements of ANB angle.

Results

High correlation and concordance of the averaged and single measurements, but no significant difference, was found between the two ultrasonographers. No statistically significant difference was found between the two methods for measuring averaged soft tissue thickness, but a 20% difference was found for the single measurements. High correlation and concordance between the ultrasonographic and radiographic measurements, but no significant difference, was found between the single and averaged ANB angle measurements.

Conclusion

Ultrasonography seems to be a noninvasive and reliable technique for measurement of the ANB angle and may replace radiographic measurement in some cases.

http://ift.tt/2nzTLHf

Trimethylation and Acetylation of β-Catenin at Lysine 49 Represent Key Elements in ESC Pluripotency

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Katrin Hoffmeyer, Dirk Junghans, Benoit Kanzler, Rolf Kemler
Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra). Furthermore, β-catMe3 and β-catAc are alternatively enriched on repressed or activated genes, respectively, during ESC and adult stem cell differentiation into neuronal or mesodermal progenitor cell lineages. Importantly, expression of a β-catenin K49A mutant results in major defects in ESC differentiation. We conclude that β-catenin K49 trimethylation and acetylation are key elements in regulating ESC pluripotency and differentiation potential.

Graphical abstract

Teaser

In ESCs, Wnt/β-catenin signaling induces mesodermal and inhibits neuronal differentiation. Hoffmeyer et al. show that β-catenin is trimethylated by Ezh2 at K49 and associated with gene repression. K49 is also acetylated by Cbp, resulting in the activation of genes. Thus, post-translational modifications of K49 represent a molecular switch for β-catenin function.


http://ift.tt/2n60eqx

Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Chunhui Wang, John R. Christin, Maja H. Oktay, Wenjun Guo
Delineating the mammary differentiation hierarchy is important for the study of mammary gland development and tumorigenesis. Mammary luminal cells are considered a major origin of human breast cancers. However, how estrogen-receptor-positive (ER⁺) and ER⁻ luminal cells are developed and maintained remains poorly understood. The prevailing model suggests that a common stem/progenitor cell generates both cell types. Through genetic lineage tracing in mice, we find that SOX9-expressing cells specifically contribute to the development and maintenance of ER⁻ luminal cells and, to a lesser degree, basal cells. In parallel, PROM1-expressing cells give rise only to ER⁺ luminal cells. Both SOX9⁺ and PROM1⁺ cells specifically sustain their respective lineages even after pregnancy-caused tissue remodeling or serial transplantation, demonstrating characteristic properties of long-term repopulating stem cells. Thus, our data reveal that mouse mammary ER⁺ and ER⁻ luminal cells are two independent lineages that are maintained by distinct stem cells, providing a revised mammary epithelial cell hierarchy.

Graphical abstract

Teaser

Wang et al. discovered two distinct lineage-biased stem cells in the mouse mammary gland: one contributes to the development of estrogen-receptor-negative luminal cells, and the other maintains the development of estrogen-receptor-positive luminal cells. These findings provide a new framework for studying mammary differentiation and breast cancer etiology.


http://ift.tt/2n5XxFu

PHD2 Targeting Overcomes Breast Cancer Cell Death upon Glucose Starvation in a PP2A/B55α-Mediated Manner

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Giusy Di Conza, Sarah Trusso Cafarello, Xingnan Zheng, Qing Zhang, Massimiliano Mazzone
B55α is a regulatory subunit of the PP2A phosphatase. We have recently found that B55α-associated PP2A promotes partial deactivation of the HIF-prolyl-hydroxylase enzyme PHD2. Here, we show that, in turn, PHD2 triggers degradation of B55α by hydroxylating it at proline 319. In the context of glucose starvation, PHD2 reduces B55α protein levels, which correlates with MDA-MB231 and MCF7 breast cancer cell death. Under these conditions, PHD2 silencing rescues B55α degradation, overcoming apoptosis, whereas in SKBR3 breast cancer cells showing resistance to glucose starvation, B55α knockdown restores cell death and prevents neoplastic growth in vitro. Treatment of MDA-MB231-derived xenografts with the glucose competitor 2-deoxy-glucose leads to tumor regression in the presence of PHD2. Knockdown of PHD2 induces B55α accumulation and treatment resistance by preventing cell apoptosis. Overall, our data unravel B55α as a PHD2 substrate and highlight a role for PHD2-B55α in the response to nutrient deprivation.

Graphical abstract

Teaser

Di Conza et al. show that, following glucose starvation, a high αKG-to-fumarate ratio favors PHD2 activation that promotes apoptosis by degrading B55α. In breast cancer cells, PHD2 knockdown prevents B55α degradation and overcomes apoptosis in response to glucose starvation. PHD2-silenced MDA-MB231 xenografts show accumulation of B55α and resistance to 2DG treatment.


http://ift.tt/2n5OGn3

Human RAD52 Captures and Holds DNA Strands, Increases DNA Flexibility, and Prevents Melting of Duplex DNA: Implications for DNA Recombination

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Ineke Brouwer, Hongshan Zhang, Andrea Candelli, Davide Normanno, Erwin J.G. Peterman, Gijs J.L. Wuite, Mauro Modesti
Human RAD52 promotes annealing of complementary single-stranded DNA (ssDNA). In-depth knowledge of RAD52-DNA interaction is required to understand how its activity is integrated in DNA repair processes. Here, we visualize individual fluorescent RAD52 complexes interacting with single DNA molecules. The interaction with ssDNA is rapid, static, and tight, where ssDNA appears to wrap around RAD52 complexes that promote intra-molecular bridging. With double-stranded DNA (dsDNA), interaction is slower, weaker, and often diffusive. Interestingly, force spectroscopy experiments show that RAD52 alters the mechanics dsDNA by enhancing DNA flexibility and increasing DNA contour length, suggesting intercalation. RAD52 binding changes the nature of the overstretching transition of dsDNA and prevents DNA melting, which is advantageous for strand clamping during or after annealing. DNA-bound RAD52 is efficient at capturing ssDNA in trans. Together, these effects may help key steps in DNA repair, such as second-end capture during homologous recombination or strand annealing during RAD51-independent recombination reactions.

Graphical abstract

Teaser

Brouwer et al. show that human RAD52 swiftly and tightly wraps ssDNA around itself. With dsDNA, interactions are weaker and diffusive but drastically change DNA mechanics, suggesting double helix intercalation. DNA-bound RAD52 efficiently captures ssDNA in trans. These features seem favorable for strand annealing, clamping, and second-end capture.


http://ift.tt/2n5VSQ1

Mammalian Diaphanous 1 Mediates a Pathway for E-cadherin to Stabilize Epithelial Barriers through Junctional Contractility

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Bipul R. Acharya, Selwin K. Wu, Zi Zhao Lieu, Robert G. Parton, Stephan W. Grill, Alexander D. Bershadsky, Guillermo A. Gomez, Alpha S. Yap
Formins are a diverse class of actin regulators that influence filament dynamics and organization. Several formins have been identified at epithelial adherens junctions, but their functional impact remains incompletely understood. Here, we tested the hypothesis that formins might affect epithelial interactions through junctional contractility. We focused on mDia1, which was recruited to the zonula adherens (ZA) of established Caco-2 monolayers in response to E-cadherin and RhoA. mDia1 was necessary for contractility at the ZA, measured by assays that include a FRET-based sensor that reports molecular-level tension across αE-catenin. This reflected a role in reorganizing F-actin networks to form stable bundles that resisted myosin-induced stress. Finally, we found that the impact of mDia1 ramified beyond adherens junctions to stabilize tight junctions and maintain the epithelial permeability barrier. Therefore, control of tissue barrier function constitutes a pathway for cadherin-based contractility to contribute to the physiology of established epithelia.

Graphical abstract

Teaser

Adherens junctions are contractile structures. Acharya et al. find that the formin mDia1 regulates F-actin organization for effective contractility. mDia1-dependent junctional tension also stabilized components of the tight junction to regulate transepithelial permeability, suggesting that junctional contractility is an element that supports the essential barrier function of post-morphogenetic epithelia.


http://ift.tt/2n5XDwO

β-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Laura J. Stoppel, Benjamin D. Auerbach, Rebecca K. Senter, Anthony R. Preza, Robert J. Lefkowitz, Mark F. Bear
Synaptic protein synthesis is essential for modification of the brain by experience and is aberrant in several genetically defined disorders, notably fragile X (FX), a heritable cause of autism and intellectual disability. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu5), yet how mGlu5 couples to the intracellular signaling pathways that regulate mRNA translation is poorly understood. Here, we provide evidence that β-arrestin2 mediates mGlu5-stimulated protein synthesis in the hippocampus and show that genetic reduction of β-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr1^−/y mouse model of FX. Importantly, reducing β-arrestin2 does not induce psychotomimetic activity associated with full mGlu5 inhibitors and does not affect Gq signaling. Thus, in addition to identifying a key requirement for mGlu5-stimulated protein synthesis, these data suggest that β-arrestin2-biased negative modulators of mGlu5 offer significant advantages over first-generation inhibitors for the treatment of FX and related disorders.

Graphical abstract

Teaser

Stoppel et al. find that β-arrestin2 is a critical link between mGlu5 and activity-dependent neuronal protein synthesis. Reducing β-arrestin2 levels corrects many synaptic and cognitive deficits in a mouse model of fragile X.


http://ift.tt/2n68V4g

Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Manuel J. Muñoz, Nicolás Nieto Moreno, Luciana E. Giono, Adrián E. Cambindo Botto, Gwendal Dujardin, Giulia Bastianello, Stefania Lavore, Antonio Torres-Méndez, Carlos F.M. Menck, Benjamin J. Blencowe, Manuel Irimia, Marco Foiani, Alberto R. Kornblihtt
We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation.

Graphical abstract

Teaser

Muñoz et al. find that UV-induced DNA damage is the main determinant affecting gene expression in response to UV in skin cells. DNA repair and the subsequent activation of ATR modulate RNAPII phosphorylation and alternative splicing patterns specifically in keratinocytes.


http://ift.tt/2n5NEYr

Sirt6 Promotes DNA End Joining in iPSCs Derived from Old Mice

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Wen Chen, Nana Liu, Hongxia Zhang, Haiping Zhang, Jing Qiao, Wenwen Jia, Songcheng Zhu, Zhiyong Mao, Jiuhong Kang
Induced pluripotent stem cells (iPSCs) have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ), rather than homologous recombination (HR), is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ. Rescue experiments show that introducing a combination of Sirt6 and the Yamanaka factors during reprogramming significantly promotes DNA double-strand break (DSB) repair by activating NHEJ in iPSCs derived from old mice. Thus, our study suggests a strategy to improve the quality of iPSCs derived from old donors by activating NHEJ and stabilizing the genome.

Graphical abstract

Teaser

Chen et al. find that iPSCs from old mice show lower genomic stability and less efficient NHEJ repair than iPSCs from young mice. This decrease is rescued by overexpression of Sirt6 during reprogramming. Sirt6 binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus leading to efficient NHEJ.


http://ift.tt/2n5T4SY

The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcinoma

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Amrita M. Nargund, Can G. Pham, Yiyu Dong, Patricia I. Wang, Hatice U. Osmangeyoglu, Yuchen Xie, Omer Aras, Song Han, Toshinao Oyama, Shugaku Takeda, Chelsea E. Ray, Zhenghong Dong, Mathieu Berge, A. Ari Hakimi, Sebastien Monette, Carl L. Lekaye, Jason A. Koutcher, Christina S. Leslie, Chad J. Creighton, Nils Weinhold, William Lee, Satish K. Tickoo, Zhong Wang, Emily H. Cheng, James J. Hsieh
PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1. Our study reports a physiological preclinical ccRCC mouse model that recapitulates somatic mutations in human ccRCC and provides mechanistic and therapeutic insights into PBRM1 mutated subtypes of human ccRCC.

Graphical abstract

Teaser

Nargund et al. present a three-step process in the pathogenesis of mouse and human clear cell kidney cancer. After the loss of VHL, the loss of SWI/SNF tumor suppressor protein PBRM1/BAF180 further activates HIF1/STAT3 signaling in mouse kidney and positions mTORC1 activation as the preferred third driver event.


http://ift.tt/2n5VRvr

Inactivation of Ezh2 Upregulates Gfi1 and Drives Aggressive Myc-Driven Group 3 Medulloblastoma

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): BaoHan T. Vo, Chunliang Li, Marc A. Morgan, Ilan Theurillat, David Finkelstein, Shaela Wright, Judith Hyle, Stephanie M.C. Smith, Yiping Fan, Yong-Dong Wang, Gang Wu, Brent A. Orr, Paul A. Northcott, Ali Shilatifard, Charles J. Sherr, Martine F. Roussel
The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression. Candidate oncogenic drivers suppressed by Ezh2 included Gfi1, a proto-oncogene frequently activated in human G3 MBs. Gfi1 disruption antagonized the tumor-promoting effects of Ezh2 loss; conversely, Gfi1 overexpression collaborated with Myc to bypass effects of Trp53 inactivation in driving MB progression in primary cerebellar neuronal progenitors. Although negative regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects.

Graphical abstract

Teaser

Vo et al. show that inactivation of Ezh2 by gene editing accelerated tumor initiation and progression in a mouse model of cMyc-driven group 3 medulloblastoma. Loss of Ezh2 derepressed expression of Gfi1, an oncogenic driver that cooperates with Myc to promote medulloblastoma development.


http://ift.tt/2n63lP9

cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer Independent

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Yue Huang, Olivia I. Koues, Jiang-yang Zhao, Regina Liu, Sarah C. Pyfrom, Jacqueline E. Payton, Eugene M. Oltz
Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritize transcriptional control elements as therapeutic targets.

Graphical abstract

Teaser

Huang et al. functionally dissect cis-regulatory circuits associated with NEK6, a mitotic kinase overexpressed in B cell lymphoma. Only a subset of predicted enhancers and CTCF sites cooperatively constructs the regulatory hub of NEK6. A super-enhancer is completely dispensable for maintaining NEK6 expression and architecture in transformed B cells.


http://ift.tt/2n5T2KQ

Critical Role for GAB2 in Neuroblastoma Pathogenesis through the Promotion of SHP2/MYCN Cooperation

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Xiaoling Zhang, Zhiwei Dong, Cheng Zhang, Choong Yong Ung, Shuning He, Ting Tao, Andre M. Oliveira, Alexander Meves, Baoan Ji, A. Thomas Look, Hu Li, Benjamin G. Neel, Shizhen Zhu
Growing evidence suggests a major role for Src-homology-2-domain-containing phosphatase 2 (SHP2/PTPN11) in MYCN-driven high-risk neuroblastoma, although biologic confirmation and a plausible mechanism for this contribution are lacking. Using a zebrafish model of MYCN-overexpressing neuroblastoma, we demonstrate that mutant ptpn11 expression in the adrenal gland analog of MYCN transgenic fish promotes the proliferation of hyperplastic neuroblasts, accelerates neuroblastomagenesis, and increases tumor penetrance. We identify a similar mechanism in tumors with wild-type ptpn11 and dysregulated Gab2, which encodes a Shp2 activator that is overexpressed in human neuroblastomas. In MYCN transgenic fish, Gab2 overexpression activated the Shp2-Ras-Erk pathway, enhanced neuroblastoma induction, and increased tumor penetrance. We conclude that MYCN cooperates with either GAB2-activated or mutant SHP2 in human neuroblastomagenesis. Our findings further suggest that combined inhibition of MYCN and the SHP2-RAS-ERK pathway could provide effective targeted therapy for high-risk neuroblastoma patients with MYCN amplification and aberrant SHP2 activation.

Graphical abstract

Teaser

Sequencing studies have identified few recurrent mutations in neuroblastomas. Zhang et al. uncover a non-mutational mechanism that enhances high-risk neuroblastomagenesis: aberrant SHP2 activation through overexpression of its upstream regulator, GAB2. Combined inhibition of MYCN and the GAB2-Shp2-Mek pathway may provide an avenue for improved targeted therapy of neuroblastoma.


http://ift.tt/2n5NCjh

Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into Cancer-Specific Nuclear Bodies

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Lisa L. Hall, Meg Byron, Dawn M. Carone, Troy W. Whitfield, Gayle P. Pouliot, Andrew Fischer, Peter Jones, Jeanne B. Lawrence
This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci. Large nuclear foci of HSATII RNA form and sequester copious MeCP2 into Cancer-Associated Satellite Transcript (CAST) bodies. Hence, HSATII DNA and RNA have an exceptional capacity to act as molecular sponges and sequester chromatin regulatory proteins into abnormal nuclear bodies in cancer. The compartmentalization of regulatory proteins within nuclear structure, triggered by demethylation of "junk" repeats, raises the possibility that this contributes to further compromise of the epigenome and neoplastic progression.

Graphical abstract

Teaser

Satellite II is a prominent but poorly studied feature of human genomes. Hall et al. show that HSATII DNA and RNA can sequester PRC1 and MeCP2. In cancer, PRC1 bodies form on the demethylated 1q12 mega-satellite, while MeCP2 bodies form on HSATII RNA, potentially leading to further changes in the epigenome.


http://ift.tt/2n5HWWl

Impact of Dietary Interventions on Noncoding RNA Networks and mRNAs Encoding Chromatin-Related Factors

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Christopher D. Green, Yi Huang, Xiaoyang Dou, Liu Yang, Yong Liu, Jing-Dong J. Han
Dietary interventions dramatically affect metabolic disease and lifespan in various aging models. Here, we profiled liver microRNA (miRNA), coding, and long non-coding RNA (lncRNA) expression by high-throughput deep sequencing in mice across multiple energy intake and expenditure interventions. Strikingly, three dietary intervention network design patterns were uncovered: (1) lifespan-extending interventions largely repressed the expression of miRNAs, lncRNAs, and transposable elements; (2) protein-coding mRNAs with expression positively correlated with long lifespan are highly targeted by miRNAs; and (3) miRNA-targeting interactions mainly target chromatin-related functions. We experimentally validated miR-34a, miR-107, and miR-212-3p targeting of the chromatin remodeler Chd1 and further demonstrate that Chd1 knockdown mimics high-fat diet and aging-induced gene expression changes and activation of transposons. Our findings demonstrate lifespan-extending diets repress miRNA-chromatin remodeler interactions and safeguard against deregulated transcription induced by aging and lifespan shortening diets, events linked by microRNA, chromatin, and ncRNA crosstalk.

Graphical abstract

Teaser

Through liver RNA sequencing and microRNA sequencing in mice across multiple energy intake and expenditure interventions, Green et al. found lifespan-extending interventions largely repressed the expression of miRNAs, lncRNAs, and transposable elements; miRNAs preferentially target mRNAs whose expression positively correlated with lifespan and modulate expression by targeting genes with chromatin-related functions.


http://ift.tt/2n5NBMf

Early Developmental Exposure to dsRNA Is Critical for Initiating Efficient Nuclear RNAi in C. elegans

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Philip K. Shiu, Craig P. Hunter
RNAi has enabled researchers to study the function of many genes. However, it is not understood why some RNAi experiments succeed while others do not. Here, we show in C. elegans that pharyngeal muscle is resistant to RNAi when initially exposed to double-stranded RNA (dsRNA) by feeding but sensitive to RNAi in the next generation. Investigating this observation, we find that pharyngeal muscle cells as well as vulval muscle cells require nuclear rather than cytoplasmic RNAi. Further, we find in these cell types that nuclear RNAi silencing is most efficiently triggered during early development, defining a critical period for initiating nuclear RNAi. Finally, using heat-shock-induced dsRNA expression, we show that synMuv B class mutants act in part to extend this critical window. The synMuv-B-dependent early-development-associated critical period for initiating nuclear RNAi suggests that mechanisms that restrict developmental plasticity may also restrict the initiation of nuclear RNAi.

Graphical abstract

Teaser

C. elegans investigators have found that the progeny of worms fed double-stranded RNA often have stronger RNAi phenotypes than the parental generation. Shiu and Hunter show that this is explained, for some tissues, by a necessity for nuclear RNAi, which requires dsRNA exposure during an early critical period.


http://ift.tt/2n5HHe8

The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Daniel Benhalevy, Sanjay K. Gupta, Charles H. Danan, Suman Ghosal, Hong-Wei Sun, Hinke G. Kazemier, Katrin Paeschke, Markus Hafner, Stefan A. Juranek
The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs. CNBP preferentially bound G-rich elements in the target mRNA coding sequences, most of which were previously found to form G-quadruplex and other stable structures in vitro. Functional analyses, including RNA sequencing, ribosome profiling, and quantitative mass spectrometry, revealed that CNBP binding did not influence target mRNA abundance but rather increased their translational efficiency. Considering that CNBP binding prevented G-quadruplex structure formation in vitro, we hypothesize that CNBP is supporting translation by resolving stable structures on mRNAs.

Graphical abstract

Teaser

Benhalevy et al. characterize the RNA-binding protein CNBP/ZNF9 using systems-wide approaches. They find that CNBP preferentially binds at mRNA regions previously found to form G-quadruplex and other structures in vitro. Ribosome profiling revealed that CNBP enhances translation across these sites, which potentially form roadblocks for the ribosome.


http://ift.tt/2n60Cp8

Tissue Myeloid Progenitors Differentiate into Pericytes through TGF-β Signaling in Developing Skin Vasculature

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Tomoko Yamazaki, Ani Nalbandian, Yutaka Uchida, Wenling Li, Thomas D. Arnold, Yoshiaki Kubota, Seiji Yamamoto, Masatsugu Ema, Yoh-suke Mukouyama
Mural cells (pericytes and vascular smooth muscle cells) are essential for the regulation of vascular networks and maintenance of vascular integrity, but their origins are diverse in different tissues and not known in the organs that arise from the ectoderm, such as skin. Here, we show that tissue-localized myeloid progenitors contribute to pericyte development in embryonic skin vasculature. A series of in vivo fate-mapping experiments indicates that tissue myeloid progenitors differentiate into pericytes. Furthermore, depletion of tissue myeloid cells and their progenitors in PU.1 (also known as Spi1) mutants results in defective pericyte development. Fluorescence-activated cell sorting (FACS)-isolated myeloid cells and their progenitors from embryonic skin differentiate into pericytes in culture. At the molecular level, transforming growth factor-β (TGF-β) induces pericyte differentiation in culture. Furthermore, type 2 TGF-β receptor (Tgfbr2) mutants exhibit deficient pericyte development in skin vasculature. Combined, these data suggest that pericytes differentiate from tissue myeloid progenitors in the skin vasculature through TGF-β signaling.

Graphical abstract

Teaser

Yamazaki et al. describe an unanticipated role of tissue-localized myeloid progenitors in pericyte development in the ectoderm-derived skin. The developmental sources of dermal pericytes are heterogeneous, and a portion of dermal pericytes has a hematopoietic/myeloid origin. Moreover, pericytes differentiate from tissue-localized myeloid progenitors through TGF-β signaling.


http://ift.tt/2n5T1GQ

Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Katrien Van der Borght, Charlotte L. Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N. Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs. In steady state, cardiac self-antigen α-myosin was presented in the heart-draining mediastinal lymph node (mLN) by cDC1s, driving the proliferation of antigen-specific CD4⁺ TCR-M T cells and their differentiation into regulatory cells (Tregs). Following MI, all DC subsets infiltrated the heart, whereas only cDCs migrated to the mLN. Here, cDC2s induced TCR-M proliferation and differentiation into interleukin-(IL)-17/interferon-(IFN)γ-producing effector cells. Thus, cardiac-specific autoreactive T cells get activated by mature DCs following myocardial infarction.

Graphical abstract

Teaser

Van der Borght et al. demonstrate that myocardial infarction induces the priming of autoreactive CD4⁺ T cells specific for cardiac self-antigen α-myosin in the heart-draining lymph node through the maturation and migration of conventional dendritic cells. Using ex vivo co-culture systems, cDC2s are shown to be superior in presenting α-myosin.


http://ift.tt/2n5VMb7

Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Li Zhou, Ming-Zhe Liu, Qing Li, Juan Deng, Di Mu, Yan-Gang Sun
Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

Graphical abstract

Teaser

Zhou et al. used slice physiological recording combined with optogenetics to systematically study the long-range functional input from six key upstream brain areas to both serotonergic and GABAergic neurons in the dorsal raphe nucleus. The results reveal the fine circuit mechanisms that functionally balance the activity of serotonergic neurons.


http://ift.tt/2n63jqv

Structural effect of Fe3O4 nanoparticles on peroxidase-like activity for cancer therapy

Publication date: Available online 18 March 2017
Source:Colloids and Surfaces B: Biointerfaces
Author(s): Shiyan Fu, Shu Wang, Xiaodi Zhang, Anhui Qi, Zhirong Liu, Xin Yu, Chuanfang Chen, Linlin Li
Ferromagnetic nanoparticles (Fe3O4 NPs) have been proven to have the intrinsic peroxidase-like activity. This property has been used for analyte detection, tumor tissue visualization, and cancer therapy, etc. However, the effect of particle structure and morphology on its peroxidase-like activity has been rarely reported. In this work, we fabricated Fe3O4 nanoparticles with different structures (nanoclusters, nanoflowers, and nanodiamonds) by facilely tuning the pH values in the hydrothermal reaction. Their in vitro peroxidase-like activity was evaluated via chromogenic reaction of 3,3′,5,5′-tetramethylbenzidine (TMB) by the reduction of H2O2 to H2O. It was found the nanostructures had a great influence on their peroxidase-like activity, following the order of nanoclusters > nanoflowers > nanodiamonds. With this activity, the peroxidase-like activity of Fe3O4 NPs was used for cancer therapy with the addition of low-concentration H2O2. The cancer cell-killing activity was due to the intracellular generated reactive oxygen species (ROS) after endocytosis of Fe3O4 NPs into the Hela cells. It was interesting that the cell killing ability of these three kinds of Fe3O4 NPs was not consistent with the in vitro enzyme-like activity. It was deduced that the cell endocytosis of the nanoparticles along with their enzyme-like activity co-determined their cancer cell-killing performance.

Graphical abstract

http://ift.tt/2mrmPkc

Index

Publication date: 2017
Source:Advances in Imaging and Electron Physics, Volume 199





http://ift.tt/2mrcg0M

Labile Iron Potentiates Ascorbate-Dependent Reduction and Mobilization of Ferritin iron

Publication date: Available online 21 March 2017
Source:Free Radical Biology and Medicine
Author(s): Charles Badu-Boateng, Sofia Pardalaki, Claude Wolf, Sonia Lajnef, Fabienne Peyrot, Richard J. Naftalin
Ascorbate mobilizes iron from equine spleen ferritin by two separate processes. Ascorbate alone mobilizes ferritin iron with an apparent Km (ascorbate) ≈ 1.5mM. Labile iron > 2μM, complexed with citrate (10mM), synergises ascorbate-dependent iron mobilization by decreasing the apparent Km (ascorbate) to ≈ 270μM and raising maximal mobilization rate by ≈ 5-fold. Catalase reduces the apparent Km(ascorbate) for both ascorbate and ascorbate + iron dependent mobilization by ≈ 80%. Iron mobilization by ascorbate alone has a higher activation energy (Ea = 45.0 ± 5.5kJ/mole) than when mediated by ascorbate with labile iron (10μM) (Ea = 13.7 ± 2.2kJ/mole); also mobilization by iron-ascorbate has a three-fold higher pH sensitivity (pH range 6.0–8.0) than with ascorbate alone. Hydrogen peroxide inhibits ascorbate's iron mobilizing action.EPR and autochemiluminescence studies show that ascorbate and labile iron within ferritin enhances radical formation, whereas ascorbate alone produces negligible radicals. These findings suggest that iron catalysed single electron transfer reactions from ascorbate, involving ascorbate or superoxide and possibly ferroxidase tyrosine radicals, accelerate iron mobilization from the ferroxidase centre more than EPR silent, bi-dentate two-electron transfers. These differing modes of electron transference from ascorbate mirror the known mono and bidentate oxidation reactions of dioxygen and hydrogen peroxide with di-ferrous iron at the ferroxidase centre. This study implies that labile iron, at physiological pH, complexed with citrate, synergises iron mobilization from ferritin by ascorbate (50–4000μM). This autocatalytic process can exacerbate oxidative stress in ferritin-containing inflamed tissue.

Graphical abstract

http://ift.tt/2nzGAWI

Organizers and activators: Cytosolic Nox proteins impacting on vascular function

Publication date: Available online 21 March 2017
Source:Free Radical Biology and Medicine
Author(s): Katrin Schröder, Norbert Weissmann, Ralf P. Brandes
NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS) in the cardiovascular system. Of the 7 members of the Nox family, at least three depend for their activation on specific cytosolic proteins. These are p47phox and its homologue NoxO1 and p67phox and its homologue NoxA1. Also the Rho-GTPase Rac is important but as this protein has many additional functions, it will not be covered here. The Nox1 enzyme is preferentially activated by the combination of NoxO1 with NoxA1, whereas Nox2 gains highest activity with p47phox together with p67phox. As p47phox, different to NoxO1 contains an auto inhibitory region it has to be phosphorylated prior to complex formation. In the cardio-vascular system, all cytosolic Nox proteins are expressed but the evidence for their contribution to ROS production is not well established. Most data have been collected for p47phox, whereas NoxA1 has basically not yet been studied. In this article the specific aspects of cytosolic Nox proteins in the cardiovascular system with respect to Nox activation, their expression and their importance will be reviewed. Finally, it will be discussed whether cytosolic Nox proteins are suitable pharmacological targets to tamper with vascular ROS production.

Graphical abstract

http://ift.tt/2nzSoIp

Data on the effects of low iron diet on serum lipid profile in HCV transgenic mouse model

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Alice Conigliaro, Viviana Costa, Rosario Amato, Carmine Mancone
Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts. The present data indicated that low serum iron concentration is associated to i) lower serum triglycerides concentrations and ii) increased circulating LDLs. The presented original data have not been published elsewhere.



http://ift.tt/2nzAlCk

Cost and performance data for residential buildings fitted with GSHP systems in Melbourne Australia

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Qi Lu, Guillermo A. Narsilio, Gregorius Riyan Aditya, Ian W. Johnston
The data reported in this article presents actual installation costs and performance data for a selection of residential Ground Source Heat Pump (GSHP) systems in Melbourne, Australia. The installation cost data includes five main cost components: ground loop installation, head pipe installation, heat pump, mechanical room installation, and fittings. The performance data presented here includes timestamp, air temperature and thermal loading. A more comprehensive analysis of this data may be obtained from the article entitled "Economic analysis of vertical ground source heat pump systems in Melbourne" (Q. Lu, G.A. Narsilio, G.R. Aditya, I.W. Johnston, 2017) [1].



http://ift.tt/2mOnrvw

Changes in cellular signaling proteins in extracts from A549, H460, and U2OS cells treated with cisplatin or docetaxel

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Voin Petrovic, Camilla Olaisen, Animesh Sharma, Anala Nepal, Steffen Bugge, Eirik Sundby, Bård Helge Hoff, Geir Slupphaug, Marit Otterlei
Cell extracts from A549, H460, and U2OS human cancer cell lines treated with cisplatin and docetaxel were analyzed by mass spectrometry (MS) proteomic analysis. The extracts were enriched for cellular signaling proteins using a mix of three different immobilized kinase inhibitors (Purvalanol B, Bisindolylmaleimide X, and (R)-3-(4-((1-Phenylethyl)amino)thieno[2,3-d]pyrimidin-6-yl)benzoic acid (SB6-060-05)) on sepharose bead columns. Raw data is deposited in the PRIDE database [1], project number PXD005286. Data presented (Table 1) shows changes relative to untreated control for each biological replicate for the three cell lines.



http://ift.tt/2nzZ6hs

Genotoxicity kinetics in murine normoblasts as an approach for the in vivo action of difluorodeoxycytidine

Abstract

Purpose

This study analyzed the kinetics of in vivo micronucleus induction in normoblasts by determining the kinetics of difluorodeoxycytidine (dFdC)-induced micronucleated polychromatic erythrocytes (MN-PCEs) in the peripheral blood of mice. The kinetic indexes of MN-PCE induction of dFdC were correlated with the previously reported mechanisms DNA damage induction by this compound. In general, this study aimed to establish an in vivo approach for discerning the processes underlying micronucleus induction by antineoplastic agents or mutagens in general.

Methods

The frequencies of PCEs and MN-PCEs in the peripheral blood of mice were determined prior to treatment and after treatment using dFdC at doses of 95, 190, or 380 µmol/kg at 8 h intervals throughout a 72 h post-treatment.

Results

The area beneath the curve (ABC) for MN-PCE induction as a function of time, which is an index of the total effect, indicated that the dose response was directly proportional and that the effect of dFdC on micronucleus induction was reduced compared with that of aneuploidogens and monofunctional and bifunctional alkylating agents but increased compared with that of promutagens, which is consistent with our previous results. The ABC showed a single peak with a small broadness index, which indicates that dFdC has a single mechanism or concomitant mechanisms for inducing DNA breaks. The time of the relative maximal induction (T _rmi) indicated that dFdC requires more time to achieve MN-PCE induction compared with aneugens and monofunctional and bifunctional alkylating agents, although it requires a similar time to achieve MN-PCE induction as azacytidine, which is consistent with evidence showing that both agents must be incorporated into DNA for their action to be realized. The timing of maximal cytotoxicity observed with the lowest dFdC dose was correlated with the timing of the main genotoxic effect. However, early and late cytotoxic effects were detected, and these effects were independent of the genotoxic response.

Conclusions

A correlation analysis indicated that dFdC appears to induce MN-PCEs through only one mechanism or mechanisms that occur concomitantly, which could be explained by the previously reported concurrent inhibitory effects of dFdC on DNA polymerase alpha, polymerase epsilon, and/or topoisomerase. The timing of maximal cytotoxicity was correlated with the timing of maximal genotoxicity; however, an early cytotoxic effect that appeared to occur prior to the incorporation of dFdC into DNA was likely related to a previously reported inhibitory effect of dFdC on thymidylate synthase and/or ribonucleotide reductase.

http://ift.tt/2nzKnTM

Rapid on-chip apoptosis assay on human carcinoma cells based on annexin-V/quantum dot probes

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Helena Montón, Mariana Medina-Sánchez, Joan Antoni Soler, Andrzej Chałupniak, Carme Nogués, Arben Merkoçi
Despite all the efforts made over years to study the cancer expression and the metastasis event, there is not a clear understanding of its origins and effective treatment. Therefore, more specialized and rapid techniques are required for studying cell behaviour under different drug-based treatments. Here we present a quantum dot signalling-based cell assay carried out in a segmental microfluidic device that allows studying the effect of anti-cancer drugs in cultured cell lines by monitoring phosphatidylserine translocation that occurs in early apoptosis. The developed platform combines the automatic generation of a drug gradient concentration, allowing exposure of cancer cells to different doses, and the immunolabeling of the apoptotic cells using quantum dot reporters. Thereby a complete cell-based assay for efficient drug screening is performed showing a clear correlation between drug dose and amount of cells undergoing apoptosis.



http://ift.tt/2nI9LYb

A review on various electrochemical techniques for heavy metal ions detection with different sensing platforms

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): BabanKumar Bansod, Tejinder Kumar, Ritula Thakur, Shakshi Rana, Inderbir Singh
Heavy metal ions are non-biodegradable and contaminate most of the natural resources occurring in the environment including water. Some of the heavy metals including Lead (Pb), Mercury (Hg), Arsenic (As), Chromium (Cr) and Cadmium (Cd) are considered to be highly toxic and hazardous to human health even at trace levels. This leads to the requirement of fast, accurate and reliable techniques for the detection of heavy metal ions. This review presents various electrochemical detection techniques for heavy metal ions those are user friendly, low cost, provides on-site and real time monitoring as compared to other spectroscopic and optical techniques. The categorization of different electrochemical techniques is done on the basis of different types of detection signals generated due to presence of heavy metal ions in the solution matrix like current, potential, conductivity, electrochemical impedance, and electrochemiluminescence. Also, the recent trends in electrochemical detection of heavy metal ions with various types of sensing platforms including metals, metal films, metal oxides, nanomaterials, carbon nano tubes, polymers, microspheres and biomaterials have been evoked.



http://ift.tt/2nQritR

Magnetic microspheres-based cytometric bead array assay for highly sensitive detection of ochratoxin A

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Weijun Kong, Changbin Xiao, Guangyao Ying, Xiaofei Liu, Xiaohong Zhao, Ruilin Wang, Li Wan, Meihua Yang
Accurate and sensitive quantification of a specific class of mycotoxins at trace levels in complex matrices with greener approaches is of significant importance. In this study, a green and economical protocol of magnetic microspheres-based cytometric bead array (CBA) assay on indirect competitive principle was developed for sensitive and rapid detection of ochratoxin A (OTA) in malts with a small number of standard and sample solutions. The protocol included the competition of OTA in malt samples and that covalently coupled on the surface of microspheres with its monoclonal antibodies, the separation and aggregation of the magnetic microspheres, and the fluorescence detection of fluorescein isothiocyanate labeled goat anti-mouse immunoglobulin G probes. The magnetic microspheres-based CBA assay allowed for ultralow limit of detection (0.025μgkg⁻¹) for OTA and showed higher sensitivity compared with the common polystyrene beads-based CBA method. This is the first report on the magnetic microspheres-based CBA assay by using a simple and easy-to-operate magnetic separator for highly sensitive and rapid detection of OTA in complex malt samples. By consuming less solvent, time and cost, as well as fewer standard and samples, the developed green protocol expressed high potential for one-site real-time detection of trace components in complex matrices.



http://ift.tt/2nI1SBE

Simultaneous monitoring of glucose and uric acid on a single test strip with dual channels

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Jinhong Guo, Xing Ma
The conventional test strip has usually only one electrochemical reaction channel, which requires two times figure punctures for the self-management of patients suffering from both diabetes and gout. Considering the large number of such patients and for the sake of reducing their pains, we report an enzymatic test strip which can simultaneously monitor glucose and uric acid (UA) with only one fingertip blood droplet. The proposed test strip is composed of dual channels. The glucose in blood is detected in the 1st channel above on the substrate and the UA is characterized in the 2nd channel located at the bottom of the substrate. The proposed design intensively matches the requirement of those patients simultaneously suffering from diabetes and gout. We carried out comparative investigations on the proposed test strip and clinical biochemical analyser, which indicates a good agreement and proved the reliability and accuracy of the proposed test strip, as promising solution for the fast growth of family health management market.



http://ift.tt/2mHTq0s

A novel versatile microbiosensor for local hydrogen detection by means of scanning photoelectrochemical microscopy

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Fangyuan Zhao, Felipe Conzuelo, Volker Hartmann, Huaiguang Li, Stefanie Stapf, Marc M. Nowaczyk, Matthias Rögner, Nicolas Plumeré, Wolfgang Lubitz, Wolfgang Schuhmann
The development of a versatile microbiosensor for hydrogen detection is reported. Carbon-based microelectrodes were modified with a [NiFe]-hydrogenase embedded in a viologen-modified redox hydrogel for the fabrication of a sensitive hydrogen biosensor By integrating the microbiosensor in a scanning photoelectrochemical microscope, it was capable of serving simultaneously as local light source to initiate photo(bio)electrochemical reactions while acting as sensitive biosensor for the detection of hydrogen. A hydrogen evolution biocatalyst based on photosystem 1-platinum nanoparticle biocomplexes embedded into a specifically designed redox polymer was used as a model for proving the capability of the developed hydrogen biosensor for the detection of hydrogen upon localized illumination. The versatility and sensitivity of the proposed microbiosensor as probe tip allows simplification of the set-up used for the evaluation of complex electrochemical processes and the rapid investigation of local photoelectrocatalytic activity of biocatalysts towards light-induced hydrogen evolution.

Graphical abstract

http://ift.tt/2nQtfXh

Ultrasound Guided Regional Anaesthesia; 2nd edition.

No abstract available

http://ift.tt/2o2TXuO

"Hell J Nucl Med"[jour]; +18 new citations

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Hell J Nucl Med"[jour]

These pubmed results were generated on 2017/03/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2mNZSTQ

Asking Better Questions: How Presentation Formats Influence Information Search.

Author: Wu, Charley M.; Meder, Bjorn; Filimon, Flavia; Nelson, Jonathan D.

DOI: 10.1037/xlm0000374

Publication Date: POST AUTHOR CORRECTIONS, 20 March 2017

http://ift.tt/2mSK6rv

Reading Through the Life Span: Individual Differences in Psycholinguistic Effects.

Author: Davies, Rob A. I.; Arnell, Ruth; Birchenough, Julia M. H.; Grimmond, Debbie; Houlson, Sam

DOI: 10.1037/xlm0000366

Publication Date: POST AUTHOR CORRECTIONS, 20 March 2017

http://ift.tt/2mSxVuW

Successful Treatment of Postoperative Pain After Mohs Micrographic Surgery With Onabotulinum Toxin A.

No abstract available

http://ift.tt/2nyt1H4

Optimizing Smartphones for Clinical Photography.

No abstract available

http://ift.tt/2mNd1MZ

Clinical Features and Treatment of Dermatofibrosarcoma Protuberans Affecting the Vulva: A Literature Review.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade cutaneous neoplasm with a low propensity for metastasis and a high rate of local recurrence. It typically presents as a dermal plaque or nodule on the trunk, limbs, or head and neck region. Vulvar DFSP has also been described, although it is less common. OBJECTIVE: To review the available literature and discuss the clinical course of DFSP affecting the vulva. MATERIALS AND METHODS: We reviewed the existing English-language literature on DFSP of the vulva with respect to clinical presentation, diagnosis, treatment, and outcome. RESULTS: Thirty three case reports and series were included (n = 54 patients). Vulvar DFSP most commonly presents as a slowly enlarging tender or asymptomatic mass on the labia majora, with histological findings of classic DFSP. Most patients were treated with wide local excision. Three patients were treated with Mohs micrographic surgery, which may decrease local recurrence and seems well suited for use in vulvar DFSP. CONCLUSION: This literature review comprehensively reviews and describes the clinical presentation of vulvar DFSP and the treatment options for this rare vulvar neoplasm. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nyoaWa

Intraoral Laser Hair Removal of a Palate Free Flap: Tips and Technique.

No abstract available

http://ift.tt/2mNa0vX

Herpes Zoster at the Site of Mohs Micrographic Surgery in an Immunocompromised Individual.

No abstract available

http://ift.tt/2nygUJL

Repair of a Full-Thickness Defect Involving Multiple Cosmetic Subunits of the Central Face.

No abstract available

http://ift.tt/2mN8OZi

An 18-Month Follow-up of Digital Myxoid Cysts After Therapy With Percutaneous Sclerotherapy With Polidocanol.

No abstract available

http://ift.tt/2nyx1XK

Tumor Margin Assessment With Loupe Magnification Enables Greater Histological Clearance of Facial Basal Cell Carcinomas Compared With Clinical Examination Alone.

BACKGROUND: Surgical excision of facial basal cell carcinomas (BCCs) is a balance between oncological clearance and conservation of cosmetic and functionally sensitive tissues. OBJECTIVE: To assess if loupe magnification (LM) can enhance the visual assessment of BCC tumor margins resulting in a greater histological clearance. METHODS AND MATERIALS: This prospective study randomized patients with primary facial BCCs into preoperative tumor margin assessment with LM (study group) or clinical examination alone (control group). Basal cell carcinomas were excised with a predetermined surgical margin of either 2, 3,, or 4 mm. Mean histological margin, incomplete excision rate, and method of closure were recorded and compared between LM and control groups, across a range of surgical margins. RESULTS: Ninety-four BCCs were excised from 93 patients, 47 BCCs in each group. The mean histological margin was larger in the study versus control group for each group (2-mm margin, 1.8 vs 1.4, 3-mm margin, 2.4 vs 2.3, 4-mm margin, and 3.1 vs 2.7), but only statistically significant in the 4-mm group (p = .032). There was no difference in method of closure between LM and control groups. CONCLUSION: Loupe magnification improved tumor margin assessment for facial BCC enabling a greater diameter of histological clearance. The use of LM should become a standard practice for facial BCC excision. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nylPdP

Familial acute necrotizing encephalopathy with RANBP2 mutation: The first report in Northeast Asia

Publication date: Available online 21 March 2017
Source:Brain and Development
Author(s): Yun-Jeong Lee, Su-Kyeong Hwang, So Mi Lee, Soonhak Kwon
BackgroundAcute necrotizing encephalopathy (ANE) is a rare but rapidly progressing encephalopathy following a febrile illness, commonly a viral infection. It is characterized by the features of acute encephalopathy such as seizure, alteration of consciousness, and symmetric involvement of the bilateral thalamus on neuroimaging tests. Although most ANE cases have occurred sporadically, familial or recurrent ANE has been reported in Caucasian patients, with genetic susceptibility to ANE noted in some patients due to a RANBP2 mutation. We report the cases of two Korean siblings with typical ANE and RANBP2 mutation.Case reportA 2year-old Korean girl presented with prolonged seizures and encephalopathy after two days of febrile illness. Brain computed tomography (CT) showed diffuse brain swelling and low attenuation in the bilateral thalamus. Two months later, her younger sister presented with lethargy and flurries of seizures after a Mycoplasma pneumoniae infection. Brain magnetic resonance imaging scan (MRI) showed a characteristic involvement of the bilateral thalamus, suggesting ANE. Although they received intravenous steroids and immunoglobulin, the older child died; her sister remained in a coma. Both were diagnosed with familial ANE after identifying a common missense mutation in RANBP2 (c.1754C>T: p.Thr585Met) in the younger sister and their father.ConclusionsThis report is the first case of familial ANE in Northeast Asia identifying a RANBP2 mutation with poor outcome. Due to rapidly deterioration and recurrent nature of familial ANE, genetic test of RANBP2 mutation should be considered for early diagnosis. Further studies are needed to elucidate the nature of ANE.



http://ift.tt/2nzfH50

Need of improvement of diet and life habits among university student regardless of religion professed

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Silvia Navarro-Prado, Emilio González-Jiménez, Javier S. Perona, Miguel A. Montero-Alonso, Marta López-Bueno, Jacqueline Schmidt-RioValle
At present, few studies have assessed the possible influence of culture and religion on healthy eating habits among the university population. The aim of this study was to identify differences in healthy and eating habits among university students of different religions. A cross-sectional study was performed with a sample population of 257 students (22.4 ± 4.76 y) at the campus of the University of Granada in Melilla (Spain). The quality of diet was assessed by the Healthy Eating Index (HEI) and the adherence to the Mediterranean diet by a validated score (MDS). There were a higher prevalence of overweight in Christian boys and girls compared to Muslims. Muslim students omit breakfast and dinner more often than Christians. Significant differences in sodium intake (p < 0.001) were observed among boys of Christian and Muslim faith, with significantly higher intakes in Christians. In contrast, a higher cholesterol intake (p = 0.038) was observed in Muslim girls compared to Christians. Regarding alcohol intake, its consumption being much higher among students of Christian faith. Likewise, there were no significant differences in the quality of the diet as assessed by HEI, this being of poor, together with a low adherence to the Mediterranean diet in both groups. Muslim university students have a lower risk of drinking alcohol (OR = 7.88, 95% CI = 4.27, 14.54). Few differences were found between girls and boys in both religions although the Mediterranean Diet Score was lower for girls. In conclusion, Melilla university students eat low quality foods and have little adherence to the Mediterranean diet regardless of the religion professed or gender, although Christians tend to drink more alcohol and to smoke more cigarettes and Muslims skip some meals.



http://ift.tt/2mSpvDN

Optimistic and pessimistic self-assessment of own diets is associated with age, self-rated health and weight status in Danish adults

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Mette Rosenlund Sørensen, Jeppe Matthiessen, Lotte Holm, Vibeke Kildegaard Knudsen, Elisabeth Wreford Andersen, Inge Tetens
The aim of this study was to analyse concordance between Danish adults' recorded diet quality and their own assessment of the healthiness and to examine socio-demographic, health and behavioural characteristics associated with an optimistic or pessimistic self-assessment.Data were derived from The Danish National Survey of Diet and Physical Activity 2011–2013 and included a random sample of 3014 adults (18–75 y). Diet quality was evaluated on the basis of seven-day pre-coded food diaries and categorised 'unhealthy', 'somewhat healthy' and 'healthy'. Self-assessment of the healthiness of own diets was registered via personal interviews and categorised healthy enough 'to a high degree', 'to some degree' or 'not at all/only partly'. Highly and somewhat optimistic self-assessment, respectively, were defined as assessing own diets as healthy enough to a high degree or to some degree while having unhealthy diets. Highly and somewhat pessimistic self-assessment, respectively, were defined as assessing own diets as not healthy enough or healthy enough to some degree while having healthy diets. Multiple logistic regression models were used to examine characteristics associated with optimistic and pessimistic self-assessments, respectively.Among individuals with unhealthy diets, 13% were highly optimistic and 42% somewhat optimistic about the healthiness of their diets. Among individuals with healthy diets, 14% were highly pessimistic and 51% somewhat pessimistic about the healthiness of their diets. Highly optimistic self-assessment was associated with increasing age, excellent self-rated health, normal weight and a moderate activity level. Highly pessimistic self-assessment was associated with decreasing age, good self-rated health and being obese. The findings indicate that people seem to use personal health characteristics as important references when assessing the healthiness of their diets.



http://ift.tt/2mqDdBB

Appetite disorders in cancer patients: Impact on nutritional status and quality of life

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): David E. Barajas Galindo, Alfonso Vidal-Casariego, Alicia Calleja-Fernández, Ana Hernández-Moreno, Begoña Pintor de la Maza, Manuela Pedraza-Lorenzo, María Asunción Rodríguez-García, Dalia María Ávila-Turcios, Miran Alejo-Ramos, Rocío Villar-Taibo, Ana Urioste-Fondo, Isidoro Cano-Rodríguez, María D. Ballesteros-Pomar
Cancer patients are at high risk of malnutrition due to several symptoms such as lack of appetite. The aim of this study was to determine the prevalence of different appetite disorders in cancer patients and their influence on dietary intake, nutritional status, and quality of life. We conducted a cross-sectional study of cancer patients at risk of malnutrition. Nutritional status was studied using Subjective Global Assessment, anthropometry, and grip strength. Dietary intake was evaluated with a 24-h recall, and patients were questioned about the presence of changes in appetite (none, anorexia, early satiety, or both). Quality of life was measured using EORTC-QLQ-C30. Multivariate analysis was performed using linear regression. 128 patients were evaluated. 61.7% experienced changes in appetite: 31% anorexia, 13.3% early satiety, and 17.2% both. Appetite disorders were more common in women and with the presence of cachexia. The combination of anorexia and satiety resulted in a lower weight and BMI. However, there were no significant effects on energy or macronutrient intake among different appetite alterations. Patients with a combination of anorexia and early satiety had worse overall health perception, role function, and fatigue. Appetite disorders are highly prevalent among cancer patients at risk of malnutrition. They have a significant impact on nutritional status and quality of life, especially when anorexia and early satiety are combined.



http://ift.tt/2mSoThe

Towards a reduced meat diet: Mindset and motivation of young vegetarians, low, medium and high meat-eaters

Publication date: 1 June 2017
Source:Appetite, Volume 113
Author(s): Joop de Boer, Hanna Schösler, Harry Aiking
This study provides insight into differences and similarities in the mindset and motivation of four dietary groups (young self-declared vegetarians, low, medium and high meat-eaters) to support the development of strategies for a general transition to a less meat-based diet. The paper highlights the value of the identity concept for our understanding of both vegetarians and meat eaters. The analysis involves a comparison of the four dietary groups focusing on the strength and the profile of their food-related motivation and their reasons for and against frequent meat eating. To check for the generalizability of the results, the analyses were performed in two samples of adults (aged 18–35) in the Netherlands (native Dutch, n = 357, and second generation Chinese Dutch, n = 350). In both samples, the vegetarians had the same level of food-related motivation as the other groups, but a different motivational profile and distinctive, taste- and animal-welfare related reasons to justify their abstinence from eating meat. The low and medium meat-eaters often considered health a reason to eat meat as well as to moderate meat eating, plus they liked to vary their meals. In these aspects they were different from both the vegetarians and the high meat-eaters. The findings are relevant for (non) governmental organizations that aim to influence dietary choices, as well as for businesses that operate in the market of meat substitutes.



http://ift.tt/2mqxlbH

Suspicious outbreak of ventilator-associated pneumonia caused by Burkholderia cepacia in a surgical intensive care unit

Publication date: Available online 20 March 2017
Source:American Journal of Infection Control
Author(s): LiPing Guo, Gang Li, Jian Wang, Xia Zhao, Shupeng Wang, Li Zhai, Hongbin Jia, Bin Cao
BackgroundWe reviewed Burkholderia cepacia infections in a hospital from 2013-2016 to report a suspicious outbreak that occurred in a surgical intensive care unit in 2015, and to outline the infection control measures adopted thereafter.MethodsReview of the health care–associated infection data regarding B cepacia via the surveillance system, hospital information system, electronic medical records, and laboratory information system together with the outbreak investigation was managed by the health care–associated infection control team.ResultsDuring June 1-14, 2015, 4 cases of ventilator-associated pneumonia (VAP) were identified; B cepacia was isolated from endotracheal aspirate samples. On June 16, 120 environmental samples were collected and analyzed for microbiologic differentiation. Thirteen strains of B cepacia were prominently found in the expiratory blocks of ventilators, revealing the biocontamination source. After chemical disinfection without damaging ventilator components, repeat microbiologic testing of random ventilator samples yielded negative results until July 30, 2015. Retrospective data showed that isolation rates of B cepacia strains had increased since 2014. Although the resistance phenotype of these strains varied slightly, they exhibited similar patterns of antibiotic susceptibility.ConclusionsRoutine cleaning and disinfection of ventilators, in addition to an intervention bundle, should form part of an integrated VAP prevention and management approach.



http://ift.tt/2mqw7wW

Bleeding Umbilical Nodule

No abstract available

http://ift.tt/2mNbR3Y

Low-Grade Neuroendocrine Carcinoma of the Skin (Primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review

Abstract: There is scarcity of information on primary cutaneous low-grade neoplasms commonly known as carcinoid tumors, owing to their rarity. The authors present 3 cases that were named "low-grade neuroendocrine carcinoma of the skin" (LGNECS). These occurred in the dermis and subcutis of the anterior chest or the inguinal region in the elderly. Histologically, the tumors showed infiltrating proliferation of nests of various sizes, with low-grade neuroendocrine cytologic features but without mucin production. All cases exhibited varying degrees of intraductal tumor components. On immunohistochemical examination, these tumors expressed estrogen receptor alpha, progesterone receptor, androgen receptor, gross cystic disease fluid protein 15, mammaglobin, and GATA3 as well as neuroendocrine markers. Although a literature review revealed 8 additional possible cases with no evidence of other diseases, it was difficult to determine if these were true cases of LGNECS, because of the limited information available. Based on its characteristic histologic features and immunoprofile, it can be proposed designating LGNECS as a distinct entity among cutaneous neuroendocrine tumors. Otherwise, such tumors could be misdiagnosed as mammary carcinomas (particularly when involving the skin of the breast) or as metastatic visceral neuroendocrine tumors of the skin.

http://ift.tt/2mNqtjy

Dermatofibrosarcoma Protuberans-Like Tumor With COL1A1 Copy Number Gain in the Absence of t(17;22)

Abstract: A 57-year-old woman presented with a 3-year history of a progressive firm plaque on the right cheek. Skin biopsies revealed a bland, storiform, spindle-cell proliferation involving the deep dermis and subcutaneous fat. By immunohistochemistry, the tumor cells were diffusely positive for CD34 and caldesmon with multifocal reactivity for epithelial membrane antigen and focal, weak staining for smooth muscle actin. Retinoblastoma protein expression was not detectable in tumor cells by immunohistochemistry. An interphase fluorescence in situ hybridization analysis for platelet-derived growth factor B (PDGFB) gene rearrangement was negative. A single-nucleotide polymorphism array study detected 1) a gain of chromosome segment 17q21.33-q25.3 which overlapped the entire COL1A1 gene with a breakpoint at 17q21.33, approximately 250 Kb centromeric to the 3′ end of COL1A1 gene, 2) several segmental gains on chromosome 11, and 3) an RB1 gene locus with normal copy number and allele frequency. Although the current case resembles dermatofibrosarcoma protuberans, it is unique in that it demonstrates a copy number gain of chromosome 17q in the absence of fusion of COL1A1 and PDGFB genes and an unusual immunohistochemical staining profile. The morphologic and molecular findings suggest a novel molecular variant of dermatofibrosarcoma protuberans not detectable with standard fluorescence in situ hybridization for PDGFB rearrangement. This variant appears to respond to imatinib after 9 months of follow-up.

http://ift.tt/2mNrsAt

Erythema Nodosum Leprosum–Like Lesions Are a Histopathologic Pattern in Whipple's Disease and a Sign of the Immune Reconstitution Inflammatory Syndrome: A Case Series and Review of the Literature

Abstract: Inflammatory and subcutaneous nodules can arise in treated and untreated cases of Whipple disease (WD). The inflammatory immune reconstitution syndrome describes paradoxical clinical inflammatory worsening of a preexisting condition because of a return of immune function. Clinicopathologic examination of 4 patients with WD who presented with erythema nodosum leprosum (ENL)–like lesions and the findings of a systematic review of this phenomenon revealed that ENL-like lesions occurred in predominantly middle-aged male patients who suffered from WD, mostly on the legs. Patients showed a nonvasculitic, mostly septal panniculits with neutrophils, macrophages, and lymphocytes. Numerous bacteria-laden periodic acid–Schiff + macrophages and free bacilli were detected in the dermis, as well as subcutaneous septae and adipose lobules. These lesions occurred in both untreated and treated patients as part of inflammatory immune reconstitution syndrome. In conclusion, ENL-like lesions represent a characteristic histopathologic pattern associated with WD, which can occur in different contexts whenever there is a change in the immunological status of the patient. This change can be triggered by antimicrobial treatment, immunomodulatory and immunosuppressant therapy, or occur spontaneously, rarely.

http://ift.tt/2mNuG7f

A Rare Case of a Primary Cutaneous Desmoplastic Atypical Granular Cell Tumor

Abstract: Granular cell tumors are uncommon neoplasms and a small number of these neoplasms have been reported as showing malignant behavior. Here, we report a rare case of a solitary granular cell tumor that exhibited atypical histology, including an extensive desmoplastic stroma, in a 69-year-old woman. The surgical specimen revealed localized areas of spindling cells, areas of cellular pleomorphism, and p53 overexpression. Based on previously published criteria, we classified this lesion as an atypical granular cell tumor. To date, only very few case reports have documented this desmoplastic variant of granular cell tumor. However, the classifications of benign, atypical, and malignant granular cell tumors are still controversial, owing to an overlap of morphological and immunohistochemical profiles and lack of consistent histological criteria. Additionally, it is unknown whether the histology of the desmoplastic variant in the present case is significant for the classification of granular cell tumors and prediction of patient prognosis. Regardless of these issues, awareness, and close follow-up are required because of potential recurrences of this rare variant of granular cell tumor.

http://ift.tt/2mNx9hD

Prurigo Pigmentosa—Report of 3 Cases From Brazil and Literature Review

Abstract: Prurigo pigmentosa (PP) is a rare inflammatory disease of the skin of uncertain etiology first reported in Japan. It is typified by recurrent eruptions of itching urticarial macules, papules, vesicopapules, and plaques with a reticular arrangement that quickly resolve leaving a net-like pigmentation. The disease presents specific histopathological features. Herein, 3 cases of PP in Brazilians with no Japanese ancestry are reported and a revision of all previous English-language case reports indexed on PubMed is provided. Two articles with original case reports not listed on PubMed were also included. Our patients are 2 women and 1 man at the ages of 39, 33, and 22 years, respectively. All 3 presented findings in consonance with previous cases of PP and were diagnosed based on clinicopathological correlation. They were successfully treated with oral minocycline or doxycycline. In our literature review, a total of 210 previously reported cases were included. Although PP seemed to be restricted to Japanese patients in the first years after its recognition, the geographic boundaries of the disease are continuously expanding. Korea responded for 83 previous cases and Japan for 53. The mean age was 24.4 years, with 84.3% of the cases occurring between 11 and 30 years of age. The female/male rate was 2.6 and the most affected anatomical sites were back, chest, and neck. We do believe that the rarity of case reports in western countries may represent lack of awareness about the disease by dermatologists and dermatopathologists in these regions.

http://ift.tt/2mNqEvu

A Rare Case of Solitary Hemorrhagic Mycosis Fungoides With Angiocentric Features

Abstract: Unilesional (solitary) mycosis fungoides (MF) is a rare variant characterized clinically by the presence of a single contiguous area of skin involvement covering less than 5% of the body surface and histopathologically by features identical to those seen in classical MF. Angiocentricity (angiodestruction) is mostly a feature of primary or secondary cutaneous lymphomas with an aggressive course and poor outcome, with only very few reports of MF with angiocentric pattern. The authors report an unusual case of solitary patch-stage MF with hemorrhagic features, characterized histologically by epidermotropic and angiocentric (angiodestructive) infiltrate and a reactive B-cell component appearing as lymphoid follicles.

http://ift.tt/2mNuNzl

Squared-Off Nuclei and “Appliqué” Pattern as a Histopathological Clue to Periocular Sebaceous Carcinoma: A Clinicopathological Study of 50 Neoplasms From 46 Patients

Abstract: The histopathological diagnosis of periocular sebaceous carcinoma can be difficult in poorly differentiated cases showing few mature sebocytes. The authors examined 50 periocular sebaceous carcinomas from 46 patients to determine the frequency of 2 features seen in this neoplasm, namely cells with squared-off nuclei and so-called "appliqué" pattern (peritumoral subnecrosis of peripherally located neoplastic cells). Neoplastic cells with squared-off nuclei were found in varying numbers in both the intraepithelial and dermal (invasive) components in all neoplasms, whereas the appliqué pattern was observed in a third of the cases. It is concluded that these features, taken together, may serve as a clue for the diagnosis of periocular sebaceous carcinoma.

http://ift.tt/2mNwnRQ

Reply to: Direct Immunofluorescence Findings in Discoid Lupus Erythematosus and Bullous Pemphigoid

No abstract available

http://ift.tt/2nyNlrP

GATA3 and MYB Expression in Cutaneous Adnexal Neoplasms

Abstract: Knowledge of staining pattern of certain immunostains might be useful in the classification of cutaneous adnexal tumors that can have clinical importance. We studied GATA3 and MYB expression in archival materials of 220 adnexal tumors comprised of sebaceous carcinomas, follicular tumors, apocrine carcinoma, predominantly apocrine tumors, predominantly eccrine tumors, and others including adenoid cystic carcinomas. Nuclear GATA3 expression was seen in 70% (153/220) of cases, including sebaceous carcinoma (93%), apocrine carcinoma (93%), follicular neoplasms (100%), and predominantly apocrine neoplasms (69%), yet only 38% of predominantly eccrine neoplasms. Nuclear MYB expression was seen in 43% (81/188) of cases, including adenoid cystic carcinoma (90%), predominantly apocrine tumors (66%), follicular neoplasms (49%), apocrine carcinomas (14%), predominantly eccrine tumors (11%), and sebaceous carcinomas (4%). GATA3 and MYB expression were noted in 43% (9/21) and 24% (5/21) of cutaneous metastases, respectively. Expression of both GATA3 and MYB was noted in 33% (60/184) of primary adnexal tumors versus 19% (4/21) of cutaneous metastases. GATA3 preferentially labels tumors with follicular, sebaceous, and apocrine differentiation. MYB is potentially a helpful stain in the distinction of desmoplastic trichoepithelioma versus basal cell carcinoma. The coexpression of GATA3 and MYB might be helpful in the distinction of primary cutaneous adnexal carcinoma versus metastatic breast, salivary gland, or urothelial carcinoma.

http://ift.tt/2nyW25n

MSH6, Past and Present and Muir–Torre Syndrome—Connecting the Dots

Abstract: Sebaceous neoplasms such as adenoma, sebaceoma, and carcinoma, although sporadic in their occurrence, are clinically significant because of their association with Muir–Torre syndrome (MTS). MTS is a rare autosomal dominant genodermatosis characterized by the occurrence of sebaceous neoplasms and/or keratoacanthomas and visceral malignancies. MTS is usually the result of germline mutations in the DNA mismatch repair genes MSH2 and, albeit less commonly, MLH1. Although less know, MSH6 is yet another key player. Evidence from Lynch syndrome indicates that pathogenic germline mutations in MSH6 are typically microsatellite stable and have a clinical presentation that differs from that associated with germline mutations in MSH2 and/or MLH1. Given this unique mutator phenotype of MSH6, the primary aim of this review was to underscore the clinical manifestations associated with pathogenic mutations in MSH6 in patients with MTS. As the current clinical and laboratory work-up of MTS is geared toward patients harboring a germline mutation in MSH2 and/or MLH1, an additional aim was to provide a scaffolding for the work-up of a patient presenting with an isolated germline mutation in MSH6.

http://ift.tt/2nyCCNL

Bleeding Umbilical Nodule

No abstract available

http://ift.tt/2mNufcW

Cutaneous Mastocytosis With Atypical Mast Cells in a 7-Year-Old Girl

Abstract: Cutaneous mastocytosis is defined by the presence of mast cells within the skin in the absence of other criteria for the diagnosis of systemic mastocytosis. Mast cells are characterized by an abundant granular cytoplasm and a round to oval or spindle-shaped nuclei. The presence of mast cells with bilobed and multilobed nuclei in cutaneous mastocytosis is a rare phenomenon and has been rarely reported in the literature. To our knowledge, there are only 4 reported cases of cutaneous mastocytosis with atypical mast cells. We hereby report a case of urticaria pigmentosa in a 7-year-old female patient. The patient presented with asymptomatic skin lesions of several years duration over the neck and left scapular area. Histopathological examination revealed the presence of middermal perivascular infiltrates mainly composed of mast cells, few lymphocytes, and eosinophils. Most mast cells showed pleomorphic nuclei with bilobed and multilobed morphology that revealed a positive expression for CD117, tryptase, CD68, and Giemsa stains. Based on these findings the diagnosis of urticaria pigmentosa with atypical mast cells was made. Additional tests to rule out systemic involvement were performed. All values, including a tryptase level, were within normal limits. No changes were noted after 1-year follow-up.

http://ift.tt/2mNjQ0Y