bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition
Authors: Kushimoto Shigeki , Endo Tomoyuki , Yamanouchi Satoshi , Sakamoto Teruo , Ishikura Hiroyasu , Kitazawa Yasuhide , Taira Yasuhiko , Okuchi Kazuo , Tagami Takashi , Watanabe Akihiro , Yamaguchi Junko , Yoshikawa Kazuhide , Sugita Manabu , Kase Yoichi , Kanemura Takashi , Takahashi Hiroyuki , Kuroki Yuuichi , Izumino Hiroo , Rinka Hiroshi , Seo Ryutarou , Takatori Makoto , Kaneko Tadashi , Nakamura Toshiaki , Irahara Takayuki , Saito Nobuyuki ,   the PiCCO Pulmonary Edema Study Group
Published: July 2013

Introduction

The Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity.

Methods

The extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe.

Results

Compared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO2/FIO2 ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO2/FIO2 ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO2/FIO2 ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001).

Conclusions

Severity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability.

Trial registration

UMIN-CTR ID UMIN000003627
Storage of bronchoalveolar lavage fluid and accuracy of microbiologic diagnostics in the ICU: a prospective observational study
Authors: Kneidinger Nikolaus , Warszawska Joanna , Schenk Peter , Fuhrmann Valentin , Bojic Andja , Hirschl Alexander , Herkner Harald , Madl Christian , Makristathis Athanasios
Published: July 2013

Introduction

Early initiation of appropriate antimicrobial treatment is a cornerstone in managing pneumonia. Because microbiologic processing may not be available around the clock, optimal storage of specimens is essential for accurate microbiologic identification of pathogenetic bacteria. The aim of our study was to determine the accuracy of two commonly used storage approaches for delayed processing of bronchoalveolar lavage in critically ill patients with suspected pneumonia.

Methods

This study included 132 patients with clinically suspected pneumonia at two medical intensive care units of a tertiary care hospital. Bronchoalveolar lavage samples were obtained and divided into three aliquots: one was used for immediate culture, and two, for delayed culture (DC) after storage for 24 hours at 4°C (DC4) and -80°C (DC-80), respectively.

Results

Of 259 bronchoalveolar lavage samples, 84 (32.4%) were positive after immediate culture with 115 relevant culture counts (≥104 colony-forming units/ml). Reduced (<104 colony-forming units/ml) or no growth of four and 57 of these isolates was observed in DC4 and DC-80, respectively. The difference between mean bias of immediate culture and DC4 (-0.035; limits of agreement, -0.977 to 0.906) and immediate culture and DC-80 (-1.832; limits of agreement, -4.914 to 1.267) was -1.788 ± 1.682 (P < 0.0001). Sensitivity and negative predictive value were 96.5% and 97.8% for DC4 and 50.4% and 75.4% for DC-80, respectively; the differences were statistically significant (P < 0.0001).

Conclusions

Bronchoalveolar lavage samples can be processed for culture when stored up to 24 hours at 4°C without loss of diagnostic accuracy. Delayed culturing after storage at -80°C may not be reliable, in particular with regard to Gram-negative bacteria.
Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder
Authors: Groenman Annabeth P. , Oosterlaan Jaap , Rommelse Nanda N. J. , Franke Barbara , Greven Corina U. , Hoekstra Pieter J. , Hartman Catharina A. , Luman Marjolein , Roeyers Herbert , Oades Robert D. , Sergeant Joseph A. , Buitelaar∗ Jan K. , Faraone∗ Stephen V.
Published: July 2013

Background

Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence.

Aims

To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD case–control study.

Method

At baseline we assessed ADHD, conduct disorder and oppositional defiant disorder. Substance use disorders, nicotine dependence and stimulant treatment were assessed retrospectively after a mean follow-up of 4.4 years, at a mean age of 16.4 years.

Results

Stimulant treatment of ADHD was linked to a reduced risk for substance use disorders compared with no stimulant treatment, even after controlling for conduct disorder and oppositional defiant disorder (hazard ratio (HR) = 1.91, 95% Cl 1.10−3.36), but not to nicotine dependence (HR = 1.12, 95% Cl 0.45−2.96). Within the stimulant-treated group, a protective effect of age at first stimulant use on substance use disorder development was found, which diminished with age, and seemed to reverse around the age of 18.

Conclusions

Stimulant treatment appears to lower the risk of developing substance use disorders and does not have an impact on the development of nicotine dependence in adolescents with ADHD.
HIV-1 Vpr Enhances PPARβ/δ-Mediated Transcription, Increases PDK4 Expression, and Reduces PDC Activity
Authors: Shrivastav Shashi , Zhang Liyan , Okamoto Koji , Lee Hewang , Lagranha Claudia , Abe Yoshifusa , Balasubramanyam Ashok , Lopaschuk Gary D. , Kino Tomoshige , Kopp Jeffrey B.
Published: July 2013

HIV infection and its therapy are associated with disorders of lipid metabolism and bioenergetics. Previous work has suggested that viral protein R (Vpr) may contribute to the development of lipodystrophy and insulin resistance observed in HIV-1–infected patients. In adipocytes, Vpr suppresses mRNA expression of peroxisomal proliferator-activating receptor-γ (PPARγ)-responsive genes and inhibits differentiation. We investigated whether Vpr might interact with PPARβ/δ and influence its transcriptional activity. In the presence of PPARβ/δ, Vpr induced a 3.3-fold increase in PPAR response element-driven transcriptional activity, a 1.9-fold increase in pyruvate dehydrogenase kinase 4 (PDK4) protein expression, and a 1.6-fold increase in the phosphorylated pyruvate dehydrogenase subunit E1α leading to a 47% decrease in the activity of the pyruvate dehydrogenase complex in HepG2 cells. PPARβ/δ knockdown attenuated Vpr-induced enhancement of endogenous PPARβ/δ-responsive PDK4 mRNA expression. Vpr induced a 1.3-fold increase in mRNA expression of both carnitine palmitoyltransferase I (CPT1) and acetyl-coenzyme A acyltransferase 2 (ACAA2) and doubled the activity of β-hydroxylacyl coenzyme A dehydrogenase (HADH). Vpr physically interacted with the ligand-binding domain of PPARβ/δ in vitro and in vivo. Consistent with a role in energy expenditure, Vpr increased state-3 respiration in isolated mitochondria (1.16-fold) and basal oxygen consumption rate in intact HepG2 cells (1.2-fold) in an etomoxir-sensitive manner, indicating that the oxygen consumption rate increase is β-oxidation–dependent. The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and β-oxidation were reversed by specific PPARβ/δ antagonists. These results support the hypothesis that Vpr contributes to impaired energy metabolism and increased energy expenditure in HIV patients.
Starting Again from the Top
Authors: Berardi Franco “Bifo”
Published: July 2013

Franco Berardi narrates his initial encounter with Antonio Negri in 1967 and his growing involvement with Potere Operaio (Workers' Power), which led to his expulsion from the Italian Communist Party, of which he had been a dissident member. He discusses the emergence of Autonomia, its suppression by the Italian state, and the flight of its members into exile abroad. He credits Negri with the important recognition that the European Left has been and continues to be too focused on the level of national politics when it should instead focus its militant energy on the transnational level.
Books for Burning
Authors: Emery Ed
Published: July 2013

This essay narrates the author's experiences as a militant translator and publisher of Italian Autonomist Marxism, including many works by Antonio Negri, from the seventies to the present. He describes his recent discussions with Negri, and his personal indignation at finding the results of his labor posted free on the Internet is ironically compared with the collective indignation expressed by anticapitalist struggles in Europe, Africa, and the Arab world. The essay also assesses the contemporary value of Negri's thought, particularly the notions of the multitude and the common, for the analysis of and resistance to cognitive capitalism.
Signaling inputs to invadopodia and podosomes
Authors: Hoshino Daisuke , Branch Kevin M. , Weaver Alissa M.
Published: July 2013

Remodeling of extracellular matrix (ECM) is a fundamental cell property that allows cells to alter their microenvironment and move through tissues. Invadopodia and podosomes are subcellular actin-rich structures that are specialized for matrix degradation and are formed by cancer and normal cells, respectively. Although initial studies focused on defining the core machinery of these two structures, recent studies have identified inputs from both growth factor and adhesion signaling as crucial for invasive activity. This Commentary will outline the current knowledge on the upstream signaling inputs to invadopodia and podosomes and their role in governing distinct stages of these invasive structures. We discuss invadopodia and podosomes as adhesion structures and highlight new data showing that invadopodia-associated adhesion rings promote the maturation of already-formed invadopodia. We present a model in which growth factor stimulation leads to phosphoinositide 3-kinase (PI3K) activity and formation of invadopodia, whereas adhesion signaling promotes exocytosis of proteinases at invadopodia.
The role of integrin-linked kinase in the molecular architecture of focal adhesions
Authors: Elad Nadav , Volberg Tova , Patla Israel , Hirschfeld-Warneken Vera , Grashoff Carsten , Spatz Joachim P. , Fässler Reinhard , Geiger Benjamin , Medalia Ohad
Published: July 2013

Integrin-mediated focal adhesions (FAs) are large, multi-protein complexes that link the actin cytoskeleton to the extracellular matrix and take part in adhesion-mediated signaling. These adhesions are highly complex and diverse at the molecular level; thus, assigning particular structural or signaling functions to specific components is highly challenging. Here, we combined functional, structural and biophysical approaches to assess the role of a major FA component, namely, integrin-linked kinase (ILK), in adhesion formation. We show here that ILK plays a key role in the formation of focal complexes, early forms of integrin adhesions, and confirm its involvement in the assembly of fibronectin-bound fibrillar adhesions. Examination of ILK-null fibroblasts by cryo-electron tomography pointed to major structural changes in their FAs, manifested by disarray of the associated actin filaments and an increase in the packing density of FA-related particles (FARPs). Interestingly, adhesion of the mutant cells to the substrate required a higher ligand density than control cells. These data indicate that ILK has a key role in integrin adhesion assembly and sub-structure, and in the regulation of the FA-associated cytoskeleton.
Collagen architecture in pregnancy-induced protection from breast cancer
Authors: Maller Ori , Hansen Kirk C. , Lyons Traci R. , Acerbi Irene , Weaver Valerie M. , Prekeris Rytis , Tan Aik-Choon , Schedin Pepper
Published: July 2013

Reduction in breast cancer risk attributed to early-age pregnancy is mediated in part by changes in the mammary epithelium. Here, we address the role of the mammary stroma in this protection. Utilizing tumor cells capable of transitioning from indolent to proliferative/invasive states, we demonstrate that mammary extracellular matrix from parous rats (parous matrix) decreases tumor growth and impedes cellular phenotypes associated with tumor cell invasion compared to nulliparous matrix. Proteomic analysis identifies increased abundance of collagen I in parous matrix, an observation extended to breast tissue of parous women. Given the pro-tumorigenic attributes of fibrillar collagen, these results were unexpected. Second harmonic generation imaging and atomic force microscopy revealed that the abundant collagen observed in the mammary glands of parous rats is less linearized and associated with a decrease in stromal stiffness, implicating collagen organization and stiffness in parity-induced protection. Using 3D cell culture models, we demonstrate that linearized/fibrillar collagen I induces cellular phenotypes consistent with an invasive behavior in mammary tumor cells and alters β1 integrin subcellular distribution. Conversely, high density, non-fibrillar collagen I induces tumor suppressive attributes including increases in junctional E-cadherin in tumor cells, upregulation of cell-cell junction genes, and downregulation of mesenchymal and metalloproteinase genes. These data show that collagen organization, rather than density alone, is a key contributor to the invasive phenotype. Further, our data show that parity alters the composition and organization of mammary ECM, particularly fibrillar collagen, in a manner consistent with tumor suppression.
Rac1 is deactivated at integrin activation sites via an IQGAP1/filamin-A/RacGAP1 pathway
Authors: Jacquemet Guillaume , Morgan Mark R. , Byron Adam , Humphries Jonathan D. , Choi Colin K. , Chen Christopher S. , Caswell Patrick T. , Humphries Martin J.
Published: July 2013

Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are required for directional migration. While the pathways that control integrin-mediated Rac1 activation are reasonably well defined, the mechanisms that are responsible for switching off activity are poorly understood. Here, proteomic analyses of activated integrin-associated complexes suggested filamin-A and IQ motif-containing GTPase activating protein 1 (IQGAP1) as candidates that might link β1 integrin to Rac1. siRNA-mediated knock down of either filamin-A or IQGAP1 induced high, dysregulated Rac1 activity during cell spreading on fibronectin. Using immunoprecipitation and immunocytochemistry, filamin-A and IQGAP1 were shown to be part of a complex that is recruited to active β1 integrin. Mass spectrometric analyses of individual filamin-A, IQGAP1 and Rac1 pull-downs, following by biochemical analyses, identified RacGAP1 as a novel IQGAP1 binding partner. Further immunoprecipitation and immunocytochemistry analyses demonstrated RacGAP1 recruitment to IQGAP1 and to active β1 integrin, and suppression of RacGAP1 expression triggered elevated Rac1 activity during spreading on fibronectin. Consistent with these findings, reduced expression of filamin-A, IQGAP1 or RacGAP1 triggered unconstrained membrane protrusion and disrupted directional cell migration on fibrillar extracellular matrices. These findings lead to a model whereby integrin engagement, followed by filamin-A, IQGAP1 and RacGAP1 recruitment, deactivates Rac1 to constrain its activity spatially and thereby co-ordinate directional cell migration.
Tumor angiogenesis is caused by single melanoma cells in a reactive oxygen species and NF-κB dependent manner
Authors: Schaafhausen Maximilian K. , Yang Wan-Jen , Centanin Lazaro , Wittbrodt Joachim , Bosserhoff Anja , Fischer Andreas , Schartl Manfred , Meierjohann Svenja
Published: July 2013

Melanomas have a high angiogenic potential, but respond poorly to medical treatment and metastasize very early. To understand the early events in tumor angiogenesis, animal models with high tumor- and blood vessel resolution are required which provide the opportunity to test small molecule inhibitors for modulating the angiogenic tumor programme. We have established a transgenic melanoma angiogenesis model in the small laboratory fish species Japanese medaka. Here, pigment cells are transformed by an oncogenic receptor tyrosine kinase in fishes expressing GFP throughout their vasculature. We show that angiogenesis occurs in a reactive oxygen species- and NF-κB-dependent, but hypoxia-independent manner. Intriguingly, we observed that blood vessel sprouting is induced even by single transformed pigment cells. The oncogenic receptor as well as human melanoma cells harbouring other oncogenes caused the production of pro-angiogenic factors, most prominently angiogenin, via NF-κB signalling. Inhibiting NF-κB prevented tumor angiogenesis and led to the regression of existing tumor blood vessels.

In conclusion, our high resolution medaka melanoma model discloses that ROS and NF-κB signaling from single tumor cells causes hypoxia-independent angiogenesis, thus demonstrating that the intrinsic malignant tumor cell features are sufficient to initiate and maintain a pro-angiogenic signaling threshold.
PIASy mediates hypoxia-induced SIRT1 transcriptional repression and epithelial-to-mesenchymal transition in ovarian cancer cells
Authors: Sun Lina , Li He , Chen Junliang , Iwasaki Yasumasa , Kubota Toru , Matsuoka Mayumi , Shen Aiguo , Chen Qi , Xu Yong
Published: July 2013

Epithelial-mesenchymal transition (EMT) plays an essential role in organogenesis and contributes to a host of pathologies including carcinogenesis. Hypoxia aids tumor metastasis in part by promoting EMT in cancer cells. The underlying mechanism whereby hypoxia orchestrates EMT remains poorly defined. Here we report that SIRT1, a multifaceted player in tumorigenesis, opposed ovarian cancer metastasis in vitro and in vivo by impeding EMT. Hypoxic stress down-regulated SIRT1 expression primarily at the transcriptional level by reducing the occupancy of the transcriptional activator Sp1 on the proximal promoter of SIRT1 gene in a SUMOylation dependent manner. Further analysis revealed that the SUMO E3 ligase PIASy was induced by hypoxia and prevented Sp1 from binding to the SIRT1 promoter. Conversely, knockdown of PIASy by small interfering RNA (siRNA) restored Sp1 binding and SIRT1 expression in cancer cells challenged with hypobaric hypoxia, reversed cancer cell EMT, and attenuated metastasis in vivo in nude mice. Importantly, analysis of human ovarian tumor specimen indicated that PIASy expression was positively, whereas SIRT1 expression was inversely, correlated with cancer aggressiveness. In summary, our work has identified a novel pathway that links SIRT1 down-regulation to hypoxia induced EMT in cancer cells and as such shed light in the development of novel anti-tumor therapeutics.
Phosphorylation of serine 4642 in the COOH-extremity of plectin by MNK2 and PKA modulates its interaction with intermediate filaments
Authors: Bouameur Jamal-Eddine , Schneider Yann , Begré Nadja , Hobbs Ryan P. , Lingasamy Prakash , Fontao Lionel , Green Kathleen J. , Favre Bertrand , Borradori Luca
Published: July 2013

Plectin is a versatile cytolinker of the plakin family conferring cell resilience to mechanical stress in stratified epithelia and muscles. It is a critical organizer of the cytoskeletal system by tethering various intermediate filament (IF) networks through its COOH-terminal IF-binding domain (IFBD). Mutations affecting the IFBD cause devastating human diseases. Here, we have found that serine 4642, located in the COOH-extremity of plectin, is phosphorylated in different cell lines. Phosphorylation of S4642 decreased the ability of plectin IFBD to associate with various IFs, as assessed by immunofluorescence microscopy and cell fractionation studies, as well as in yeast two-hybrid assays. Plectin phosphorylated at S4642 was reduced at sites of IF network anchorage along cell-substrate contacts in both skin and cultured keratinocytes. Treatment of SK-MEL-2 and HeLa cells with okadaic acid increased plectin S4642 phosphorylation suggesting that protein phosphatase 2A dephosphorylates this residue. Moreover, plectin S4642 phosphorylation was enhanced after cell treatment with EGF, phorbol ester, sorbitol, 8-bromo-cyclic AMP, as well as during wound healing and protease-mediated cell detachment. Using selective protein kinase inhibitors, we identified two different kinases modulating the phosphorylation of plectin S4642 in HeLa cells, MNK2, downstream the ERK1/2-dependent MAPK cascade, and PKA. Our study indicates that phosphorylation of S4642 has an important regulatory role in the interaction of plectin with IFs and identifies a novel link between MNK2 and the cytoskeleton.
Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking
Authors: Yang Xiaofeng , Mao Feifei , Lv Xiangdong , Zhang Zhao , Fu Lin , Lu Yi , Wu Wenqing , Zhou Zhaocai , Zhang Lei , Zhao Yun
Published: July 2013

Hedgehog (Hh) signaling pathway plays a very important role in metazoan development by controlling pattern formation. Malfunction of Hh signaling pathway leads to numerous serious human diseases, including congenital disorders and cancers. The seven-transmembrane domain protein Smoothened (Smo) is a key transducer of Hh signaling pathway, and mediates the graded Hh signal across the cell plasma membrane, thereby inducing the proper expression of downstream genes. Smo accumulation on cell plasma membrane is regulated by its C-tail phosphorylation and the graded Hh signal. The inhibitory mechanism for Smo membrane accumulation in the absence of Hh, however, is still largely unknown. Here, we report that Vps36 of ESCRT-II complex regulates Smo trafficking between cytosol and plasma membrane by specifically recognizing the ubiquitin signal on Smo in the absence of Hh. Furthermore, in the absence of Hh, Smo is ubiquitinated on its cytoplasmic part, including its internal loops and C-tail. Taken together, our data suggested that ESCRT-II complex, especially Vps36, has a special role in controlling Hh signaling by targeting the membrane protein Smo for its trafficking in the absence of Hh, thereby involving in the regulation of proper Hh signaling activity.
Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis implies functions in distinct chromosome processes
Authors: Gómez Rocío , Jordan Philip W. , Viera Alberto , Alsheimer Manfred , Fukuda Tomoyuki , Jessberger Rolf , Llano Elena , Pendás Alberto M. , Handel Mary Ann , Suja José A.
Published: July 2013

Four members of the structural maintenance of chromosome (SMC) protein family have essential functions in chromosome condensation (SMC2/4) and sister-chromatid cohesion (SMC1/3). The SMC5/6 complex has been implicated in chromosome replication, DNA repair, and chromosome segregation in somatic cells, but its possible functions during mammalian meiosis are unknown. Here, we find that in mouse spermatocytes SMC5 and SMC6 are located at the central region of the synaptonemal complex from zygotene until diplotene. During late diplotene both proteins load to the chromocenters, where they colocalize with DNA Topoisomerase IIα, and then accumulate at the inner domain of the centromeres during the first and second meiotic divisions. Interestingly, SMC6 and DNA Topoisomerase IIα colocalize at stretched strands that join kinetochores during the metaphase II to anaphase II transition, and are both observed on stretched lagging chromosomes at anaphase II following Etoposide treatment. During mitosis SMC6 and DNA Topoisomerase IIα colocalize at the centromeres and chromatid axes. Our results are consistent with the participation of SMC5 and SMC6 in homologous chromosome synapsis during prophase I, chromosome and centromere structure during meiosis I and mitosis, and, with DNA Topoisomerase IIα, in regulating centromere cohesion during meiosis II.
Examination of a second node of translational control in the unfolded protein response
Authors: Preston Amanda M. , Hendershot Linda M.
Published: July 2013

The unfolded protein response (UPR) is a largely cytoprotective signaling cascade that acts to re-establish homeostasis of the endoplasmic reticulum (ER) under conditions of stress by inducing an early and transient block in general protein synthesis and by increasing the folding and degradative capacity of the cell through an extensive transcriptional program. It is well-established that the mechanism for the early translational attenuation during ER stress occurs through phosphorylation of eukaryotic initiation factor 2 α (eIF2α) by activated PERK. Our data demonstrate that when eIF2α is dephosphorylated translation is not fully restored to pre-stressed levels. We find that this correlates with reduced mTOR activity and as a result decreased phosphorylation of 4E-BP1, which negatively regulates assembly of the eIF4F complex and cap-dependent translation. The decrease in mTOR/4E-BP1 phosphorylation is associated with activation of AMP kinase, a negative regulator of mTOR, and in the case of some stress conditions, down-regulation of signaling through key components of the PI3K pathway. Furthermore, we show that there is a subset of mRNAs that do not recover from UPR-induced translational repression, which include those whose translation is particularly sensitive to loss of eIF4F, such as cyclin D1, Bcl-2 and MMP9. Together these data implicate mTOR/4E-BP1 hypophosphorylation as a second, more restricted mechanism of translational control occurring somewhat later in the UPR.
Fragmentation Reactions of Labeled and Unlabeled Rhodamine B in a High-Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
Authors: Clemen Martin , Gernert Claus , Peters Jonathan , Grotemeyer Jürgen
Published: July 2013

The fragmentation reactions of Rhodamine B have been investigated by the use of electrospray ionization mass spectra in a high mass resolving ion cyclotron resonance mass spectrometer. Using high resolution, it could be shown that the loss of 44 mass units from the molecular ion is due to propane; the measured masses were inconsistent with loss of carbon dioxide. These conclusions are supported using deuterium-labeled Rhodamine B. This sample again only shows the loss of fully-deuterated propane verifying the high-resolution data. These findings illustrate very clearly that the conclusions based solely on low resolution spectra were false. The general implication on fragmentations of aromatic acids is discussed.
Scalable Architecture for Federated Translational Inquiries Network (SAFTINet)
Technology Infrastructure for a Distributed Data Network
Authors: Schilling Lisa M. , Kwan Bethany M. , Drolshagen Charles T. , Hosokawa Patrick W. , Brandt Elias , Pace Wilson D. , Uhrich Christopher , Kamerick Michael , Bunting Aidan , Payne Philip R.O. , Stephens William E. , George Joseph M. , Vance Mark , Giacomini Kelli , Braddy Jason , Green Mika K. , Kahn Michael G.
Published: July 2013

Introduction. Distributed Data Networks (DDNs) offer infrastructure solutions for
sharing electronic health data from across disparate data sources to support comparative
effectiveness research. Data sharing mechanisms must address technical and governance
concerns stemming from network security and data disclosure laws and best practices,
such as HIPAA.Methods. The Scalable Architecture for Federated Translational Inquiries
Network (SAFTINet) deploys TRIAD grid technology, a common data model, detailed
technical documentation, and custom software for data harmonization to facilitate data
sharing in collaboration with stakeholders in the care of safety net populations. Data
sharing partners host TRIAD grid nodes containing harmonized clinical data within their
internal or hosted network environments. Authorized users can use a central web-based
query system to request analytic data sets.Discussion. SAFTINet DDN infrastructure
achieved a number of data sharing objectives, including scalable and sustainable systems
for ensuring harmonized data structures and terminologies and secure distributed
queries. Initial implementation challenges were resolved through iterative discussions,
development and implementation of technical documentation, governance, and technology
solutions.
Dynamic Characteristics and Speed Control Strategy of Cellulose Hydrolysis Reactor at High Solids Loading
Authors: Huang Juan , Zhang Jian , He Yanqing , Bao Jie , Dai Gance
Published: July 2013

This article put emphasis on systematic research and development on cellulose hydrolysis reactor. The simultaneous saccharification and fermentation of lignocellulosic was carried out in a 5-L reactor at high solids loading of corn stover (25%, w/w). The dynamic characteristics of reactive system were examined. The experimental results showed that the lignocellulosic biomass experienced a series of morphology evolution and viscosity variation. This evolution was a typical event caused by solid reactive processing, and it constituted the basis of a new geometrical configuration of reactor (specifically hybrid impeller). The minimum rotational speed of the impeller was proposed based on the Coutte flow analogy and the yield stress concept. The macroscopic performance of the reactor changed significantly with time. In view of this effect, the operating strategy of the impeller was determined.
General aspects of drug interactions with systemic antifungals in a retrospective study sample
Authors: Schmitt Juliano Vilaverde , Bombonatto Giovana , Trierweiler Stella Maris , Fabri Andrea Buosi
Published: July 2013

A retrospective study evaluating hepatic laboratory alterations and potential drug interactions in patients treated for onychomycosis. We evaluated 202 patients, 82% female. In 273 liver enzyme tests, there were changes in only 6%. Potential drug interactions were identified in 28% of patients for imidazole and 14% for terbinafine. The risk of potential interactions increased with the patient's age and use of multiple drugs.
Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars
Authors: Camacho-Martinez Francisco Miguel , Rey Elena Rodriguez , Serrano Francisco Camacho , Wagner Adriana
Published: July 2013

While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..
Unilateral punctate porokeratosis - Case report
Authors: Teixeira Vera Barreto , Reis Jose Pedro , Vieira Ricardo , Tellechea Oscar , Figueiredo Americo
Published: July 2013

This case report involves a 20-year-old man with unilateral punctate porokeratosis. The patient presented an 8-year history of numerous asymptomatic keratotic papules and pits with linear distribution on his left pal-mar surface and fifth finger of the left hand. Histopathological examination of the keratotic plug revealed findings of distinct epidermal depressions containing cornoid lamellae. This report review draws attention to differential diagnoses of punctate porokeratosis.
Genitogluteal porokeratosis - Case report
Authors: Ferreira Flavia Regina , Lessa Priscila Pacheco , Alvarenga Marcia Lanzoni de
Published: July 2013

We report the case of a patient diagnosed with genitogluteal porokeratosis, a disorder of epidermal keratinization. The location described is extremely rare and very often late diagnosed or even misdiagnosed. Histopathology showed a typical cornoid lamella of great value to support this diagnosis. The importance of awareness of this entity by the specialist is emphasized as a differential diagnosis among genital diseases of chronic evolution and difficult treatment.
Shiitake dermatitis: the first case reported in Brazil
Authors: Adriano Andre Ricardo , Acosta Martha Liliana , Azulay David Rubem , Quiroz Carlos Daniel , Talarico Samantha Rodrigues
Published: July 2013

Shiitake Dermatitis is often presented as papules and erythemato-violaceous linear streaks. It can be associated with bleomycin treatment, dermatomyositis and shiitake mushroom (Lentinus edodes). There is not any previous report concerning this rare etiology in our country. Shiitake is the second most consumed mushroom worldwide and it can cause flagellate erythema when ingested raw or half cooked. It has a higher incidence in Oriental countries because of their eating habits, this is the first case reported in Brazil, in a male patient that presented a cutaneous rash after consuming this raw mushroom.
Proximal-type epithelioid sarcoma - Case report
Authors: Santos Luciana Mendes dos , Nogueira Lisiane , Matsuo Christiane Yuri , Talhari Carolina , Santos Monica
Published: July 2013

Epithelioid sarcoma, first described by Enzinger in 1970, is a rare soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in distal portions of the extremities of adolescents and young adults. In 1997, Guillou et al. described a different type of epithelioid sarcoma, called proximal-type epithelioid sarcoma, which is found mostly in the pelvic and perineal regions and genital tracts of young to middle-aged adults. It is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. In this paper we present a case of proximal-type epithelioid sarcoma with an aggressive clinical course, including distant metastasis and death nine months after diagnosis.
Argyria mimicking a blue nevis: dermoscopy features
Authors: Enei Maria Leonor , Paschoal Francisco Macedo , Valdes Rodrigo
Published: July 2013

Argyria is a rare disease caused by prolonged skin contact with silver. Localized cases have been described regarding the use of topical medications, and trauma with objects containing this metal such as acupuncture needles and jewelry. Clinically, a macule or a patch, round or oval, appears in the infected area, with a characteristic bluey-gray color. To our knowledge this is the first time that this clinical condition has been described through the use of dermoscopy.
Neurofibromatosis: chronological history and current issues
Authors: Antonio Joao Roberto , Goloni-Bertollo Eny Maria , Tridico Livia Arroyo
Published: July 2013

Neurofibromatosis, which was first described in 1882 by Von Recklinghausen, is a genetic disease characterized by a neuroectodermal abnormality and by clinical manifestations of systemic and progressive involvement which mainly affect the skin, nervous system, bones, eyes and possibly other organs. The disease may manifest in several ways and it can vary from individual to individual. Given the wealth of information about neurofibromatosis, we attempted to present this information in different ways. In the first part of this work, we present a chronological history, which describes the evolution of the disease since the early publications about the disorder until the conclusion of this work, focusing on relevant aspects which can be used by those wishing to investigate this disease. In the second part, we present an update on the various aspects that constitute this disease.
Biologia e tabela de vida do ácaro-vermelho Tetranychus bastosi em pinhão-manso
Authors: Pedro Neto Marçal , Sarmento Renato Almeida , Oliveira Wennder Parente de , Picanço Marcelo Coutinho , Erasmo Eduardo Andrea Lemus
Published: July 2013

O objetivo deste trabalho foi determinar a biologia e a tabela de vida de Tetranychus bastosi em pinhão-manso (Jatropha curcas). O experimento foi realizado em ambiente controlado a 26ºC e 75% de UR, com fotófase de 12 horas. Os ovos usados nos experimentos foram oriundos de criação estoque. As avaliações foram realizadas duas vezes ao dia, para a biologia do ácaro, e uma vez, para os parâmetros reprodutivos. O ciclo médio de vida das fêmeas foi de 9,63 dias e o dos machos, de 8,94 dias. A razão sexual foi 0,65 e a longevidade média das fêmeas foi de 16 dias, com produção média de 59 ovos por fêmea. Os parâmetros de tabela de vida obtidos foram: taxa líquida de reprodução (Ro), 45,41 indivíduos; duração média das gerações (T), 12,66 dias; taxa intrínseca de crescimento (r m), 0,0538 fêmea por fêmea por dia; razão finita de aumento (λ), 1,023 fêmea por fêmea; e tempo para duplicação da população (TD), 3,15 dias. O ácaro T. bastosi desenvolve-se bem e apresenta alto potencial reprodutivo sobre folhas de pinhão-manso.
Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil
Authors: Maia Marina Valente , Cunha Maria da Graça Souza , Cunha Carolina Souza
Published: July 2013

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. Results: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies had shown, no treatment was stopped due to side effects. Nevertheless, patient follow-up and studies with bigger samples are necessary to guarantee the efficacy and safety of the alternative regimen as a second-line scheme in multi-drug therapy.
Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators
Authors: Pereira Patricia Fonseca , Cuzzi Tullia , Galhardo Maria Clara Gutierrez
Published: July 2013

Kaposi's sarcoma is the most common neoplasia diagnosed in AIDS patients and the expression of the human herpesvirus-8 (HHV-8) latent nuclear antigen-1 has been useful for its histological diagnosis. The aim of this study is to confirm that immunohistochemistry is a valuable tool for differentiating KS from its simulators in skin biopsies of HIV patients. Immunohistochemical and histological analyses were performed in 49 Kaposi's sarcoma skin biopsies and 60 of its histological simulators. Positivity was present in the 49 Kaposi's sarcoma skin biopsies and no staining was observed in the 60 simulators analyzed, resulting in sensibility and specificity of 100%. HHV-8 immunohistochemical detection is an effective tool for diagnosing Kaposi's sarcoma, especially in early lesions in which neoplastic features are not evident. It also contributes to its histological differential diagnosis.
Dermoscopy of lichen aureus
Authors: Portela Poliana Santin , Melo Daniel Fernandes , Ormiga Patricia , Oliveira Felipe José da Cruz , Freitas Natália Carvalho de , Bastos Júnior Cesar Souza
Published: July 2013

Lichen aureus (also called "lichen purpuricus") is an uncommon subtype of pigmented purpuric dermatosis. Clinically characterized by rust macules, papules or plaques, it is a chronic disease which more often affects young adults and is localized mainly on the lower extremities. The diagnosis is made on the basis of clinical and histopathological features. Dermoscopy findings are useful to confirm clinical diagnosis.
Rosai-Dorfman disease presenting with extensive cutaneous manifestation - Case report
Authors: Leal Paula Azevedo Borges , Adriano Adrilena Lopes , Breckenfeld Marcelle Parente , Costa Igor Santos , Sousa Antônio Renê Diógenes de , Gonçalves Heitor de Sá
Published: July 2013

Rosai-Dorfman disease is a benign, self-limited, idiopathic proliferative histiocytic disorder. It was first described in 1969 by Rosai and Dorfman. In its typical form the disease is characterized by extensive cervical lymphadenopathy associated with fever, polyclonal gammopathy and leukocytosis with neutrophilia. The skin is the most common site affected. Extranodal manifestations have been reported in 43% of cases. In this study, we report an atypical case of Rosai-Dorfman disease in a female with massive cutaneous manifestation on the thigh, associated with a minimal lymphadenopathy limited to the regional inguinal lymph nodes.
Non Hodgkin T cell lymphoma: an atypical clinical presentation
Authors: Maio Paula , Bento Diogo , Vieira Raquel , Afonso Ana , Sachse Fernanda , Kutzner Heinz
Published: July 2013

Cytotoxic lymphomas comprise a spectrum of peripheral T-cell lymphomas that can have a initial or late cutaneous presentation. We describe a 46-year-old man from Cape Verde, with a dermatosis involving his face and trunk, consisting of monomorphic papules with a smooth surface and both motor and sensory polyneuropathy.The hypothesis of leprosy was supported by the clinical and initial hystopathological findings and the patient was referred to our hospital with suspected Hansen's disease. In the new skin and lymph node biopsies a lymphocyte population was identified whose immunohystochemistry study allowed the diagnosis of T-cell lymphoma with expression of cytotoxic markers. The patient was started on chemotherapy with initial remission of the skin lesions but, subsequently, progression of systemic disease.
Lymphangiectatic Kaposi's sarcoma in a patient with AIDS
Authors: Santos Mônica , Vilasboas Virginia , Mendes Luciana , Talhari Carolina , Talhari Sinésio
Published: July 2013

Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma.
An exploratory study on correlating the permeability of concrete with its porosity and tortuosity
Authors: Ahmad Shamsad , Azad Abul Kalam
Published: July 2013

Permeability of concrete is often used as a key material property for assessing its durability. For a porous material in general, permeability depends upon the pore characteristics (i.e. porosity and tortuosity of pore channels). In this study, an attempt has been made to observe the relationship between pore characteristics and permeability of concrete. Data pertaining to porosity, tortuosity and permeability of concrete were typically obtained by testing different concrete mixtures prepared with varying water/cement ratios, cement contents and coarse/fine aggregate ratios. The experimental data were used to explore the correlation between pore characteristics and permeability of concrete. The results show that a correlation exists between the porosity/tortuosity ratio and the permeability of concrete, the coefficient of permeability increasing with increasing porosity/tortuosity ratio. The experimentally observed correlation bears resemblance to Kozeney's theoretical formation of intrinsic permeability in which permeability is expressed as a function of the porosity/tortuosity ratio.
A long-term field study for the investigation of rainfall-induced landslides
Authors: SPRINGMAN S.M. , THIELEN A. , KIENZLER P. , FRIEDEL S.
Published: July 2013

A two-year monitoring experiment has been conducted on a slope in shallow weathered soils overlying sandstone bedrock in Toessegg, Switzerland. Water balance and suctions were measured, together with the meteorological inputs, in preparation for predicting environmental effects on slope stability. Electrical resistivity tomography proved particularly helpful in establishing the spatial distribution of soil layering, with clayey sand overlying silty sand and bedrock. This paper describes monitoring of the field measurements, and shows that the double layer causes a bi-seasonal response, with the smallest ‘factor of safety' after the wetter winter months.