bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine
Authors: Bredholt Therese , Ersvær Elisabeth , Erikstein Bjarte Skoe , Sulen André , Reikvam Håkon , Aarstad Hans Jørgen , Johannessen Anne Christine , Vintermyr Olav Karsten , Bruserud Øystein , Gjertsen Bjørn Tore
Published: July 2013

Background

Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone derivatives cathine and norephedrine, in comparison with a defined extract of the psychostimulating herb khat (Catha edulis Forsk.). Intracellular protein modifications in single cells were studied using immunostaining and flow cytometry, cell viability was determined by Annexin V-FITC/Propidium Iodide staining, and T-lymphocyte proliferation was measured by 3H-thymidine incorporation.

Results

Cathinone, cathine and norephedrine generally reduced post-translational modifications of intracellular signal transducers in T-lymphocytes, B-lymphocytes, natural killer cells and monocytes, most prominently affecting c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), p38 MAPK (p-Thr180/p-Tyr182) and p53 (both total p53 protein and p-Ser15). In contrast, the botanical khat-extract induced protein phosphorylation of STAT1 (p-Tyr701), STAT6 (p-Tyr641), c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), NF-κB (p-Ser529), Akt (p-Ser473), p38 MAPK (p-Thr180/p-Tyr182), p53 (Ser15) as well as total p53 protein. Cathinone, cathine and norephedrine resulted in unique signaling profiles, with B-lymphocytes and natural killer cells more responsive compared to T-lymphocytes and monocytes. Treatment with norephedrine resulted in significantly increased T-lymphocyte proliferation, whereas khat-extract reduced proliferation and induced cell death.

Conclusions

Single-cell signal transduction analyses of leukocytes distinctively discriminated between stimulation with cathinone and the structurally similar derivatives cathine and norephedrine. Cathinone, cathine and norephedrine reduced phosphorylation of c-Cbl, ERK1/2, p38 MAPK and p53(Ser15), and norephedrine induced T-lymphocyte proliferation. Khat-extract induced protein phosphorylation of signal transducers, p38 MAPK and p53, followed by reduced cell proliferation and cell death. This study suggests that protein modification-specific single-cell analysis of immune cells could unravel pharmacologic effects of amphetamines and amphetamine-like agents, and further could represent a valuable tool in elucidation of mechanism(s) of action of complex botanical extracts.
Identification of a neuronal transcription factor network involved in
medulloblastoma development
Authors: Łastowska Maria , Al-Afghani Hani , Al-Balool Haya H , Sheth Harsh , Mercer Emma , Coxhead Jonathan M , Redfern Chris PF , Peters Heiko , Burt Alastair D , Santibanez-Koref Mauro , Bacon Chris M , Chesler Louis , Rust Alistair G , Adams David J , Williamson Daniel , Clifford Steven C , Jackson Michael S
Published: July 2013

Background

Medulloblastomas, the most frequent malignant brain tumours affecting
children, comprise at least 4 distinct clinicogenetic subgroups. Aberrant
sonic hedgehog (SHH) signalling is observed in approximately 25% of tumours
and defines one subgroup. Although alterations in SHH pathway genes (e.g.
PTCH1, SUFU) are observed in many of these tumours,
high throughput genomic analyses have identified few other recurring
mutations. Here, we have mutagenised the Ptch
+/- murine tumour model using the Sleeping Beauty transposon
system to identify additional genes and pathways involved in SHH subgroup
medulloblastoma development.

Results

Mutagenesis significantly increased medulloblastoma frequency and identified
17 candidate cancer genes, including orthologs of genes somatically mutated
(PTEN, CREBBP) or associated with poor outcome (PTEN,
MYT1L) in the human disease. Strikingly, these candidate genes were
enriched for transcription factors (p= 2x10-5), the
majority of which (6/7; Crebbp, Myt1L, Nfia, Nfib,
Tead1 and Tgif2) were linked within a single regulatory
network enriched for genes associated with a differentiated neuronal
phenotype. Furthermore, activity of this network varied significantly
between the human subgroups, was associated with metastatic disease, and
predicted poor survival specifically within the SHH subgroup of tumours.
Igf2, previously implicated in medulloblastoma, was the most
differentially expressed gene in murine tumours with network perturbation,
and network activity in both mouse and human tumours was characterised by
enrichment for multiple gene-sets indicating increased cell proliferation,
IGF signalling, MYC target upregulation, and decreased neuronal
differentiation.

Conclusions

Collectively, our data support a model of medulloblastoma development in
SB-mutagenised Ptch
+/- mice which involves disruption of a novel transcription
factor network leading to Igf2 upregulation, proliferation of GNPs,
and tumour formation. Moreover, our results identify rational therapeutic
targets for SHH subgroup tumours, alongside prognostic biomarkers for the
identification of poor-risk SHH patients.
Autocrine IGF-I/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation
Authors: Fox Emily M , Kuba María Gabriela , Miller Todd W , Davies Barry R , Arteaga Carlos L
Published: July 2013

Introduction

Estrogen receptor α-positive (ER+) breast cancers adapt to hormone deprivation and acquire resistance to antiestrogen therapies. Upon acquisition of hormone independence, ER+ breast cancer cells increase their dependence on the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. We examined the effects of AKT inhibition and its compensatory upregulation of insulin-like growth factor (IGF)-I/InsR signaling in ER+ breast cancer cells with acquired resistance to estrogen deprivation.

Methods

Inhibition of AKT using the catalytic inhibitor AZD5363 was examined in four ER+ breast cancer cell lines resistant to long-term estrogen deprivation (LTED) by western blotting and proliferation assays. Feedback upregulation and activation of receptor tyrosine kinases (RTKs) was examined by western blotting, real-time qPCR, ELISAs, membrane localization of AKT PH-GFP by immunofluorescence and phospho-RTK arrays. For studies in vivo, athymic mice with MCF-7 xenografts were treated with AZD5363 and fulvestrant with either the ATP-competitive IGF-IR/InsR inhibitor AZD9362 or the fibroblast growth factor receptor (FGFR) inhibitor AZD4547.

Results

Treatment with AZD5363 reduced phosphorylation of the AKT/mTOR substrates PRAS40, GSK3α/β and S6K while inducing hyperphosphorylation of AKT at T308 and S473. Inhibition of AKT with AZD5363 suppressed growth of three of four ER+ LTED lines and prevented emergence of hormone-independent MCF-7, ZR75-1 and MDA-361 cells. AZD5363 suppressed growth of MCF-7 xenografts in ovariectomized mice and a patient-derived luminal B xenograft unresponsive to tamoxifen or fulvestrant. Combined treatment with AZD5363 and fulvestrant suppressed MCF-7 xenograft growth better than either drug alone. Inhibition of AKT with AZD5363 resulted in upregulation and activation of RTKs, including IGF-IR and InsR, upregulation of FoxO3a and ERα mRNAs as well as FoxO- and ER-dependent transcription of IGF-I and IGF-II ligands. Inhibition of IGF-IR/InsR or PI3K abrogated AKT PH-GFP membrane localization and T308 P-AKT following treatment with AZD5363. Treatment with IGFBP-3 blocked AZD5363-induced P-IGF-IR/InsR and T308 P-AKT, suggesting that receptor phosphorylation was dependent on increased autocrine ligands. Finally, treatment with the dual IGF-IR/InsR inhibitor AZD9362 enhanced the anti-tumor effect of AZD5363 in MCF-7/LTED cells and MCF-7 xenografts in ovariectomized mice devoid of estrogen supplementation.

Conclusions

These data suggest combinations of AKT and IGF-IR/InsR inhibitors would be an effective treatment strategy against hormone-independent ER+ breast cancer.
jMOSAiCS: joint analysis of multiple ChIP-seq datasets
Authors: Zeng Xin , Sanalkumar Rajendran , Bresnick Emery H , Li Hongda , Chang Qiang , Keleş Sündüz
Published: July 2013

The ChIP-seq technique enables genome-wide mapping of in vivo protein-DNA interactions and chromatin states. Current analytical approaches for ChIP-seq analysis are largely geared towards single-sample investigations, and have limited applicability in comparative settings that aim to identify combinatorial patterns of enrichment across multiple datasets. We describe a novel probabilistic method, jMOSAiCS, for jointly analyzing multiple ChIP-seq datasets. We demonstrate its usefulness with a wide range of data-driven computational experiments and with a case study of histone modifications on GATA1-occupied segments during erythroid differentiation. jMOSAiCS is open source software and can be downloaded from Bioconductor [1].
Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton’s jelly-derived mesenchymal stem cells
Authors: Corotchi Maria Cristina , Popa Mirel Adrian , Remes Anca , Sima Livia Elena , Gussi Ilinca , Lupu Plesu Marilena
Published: July 2013

Introduction

Human Wharton’s jelly (WJ) has become a preferred source of mesenchymal stem cells (MSCs) whose clinical applications are limited by the use of adequate xeno-free (XF), in vitro manipulation conditions. Therefore, the objective of our study was to characterize WJ-derived MSCs (WJ-MSCs), isolated by different methods and cultured in a commercially available, MSC XF medium, not least of all by investigating their endothelial differentiation capacity.

Methods

WJ explants and enzymatically dissociated WJ cells were cultured in a defined, XF medium for MSCs. Adherent cells at passages 2 and 5 were characterized as MSCs by flow cytometry, MTT, real-time quantitative reverse transcription PCR, and functional multipotent differentiation assays. The endothelial differentiation capacity of MSCs isolated and expanded until passage 2 in the MSC XF medium, and then subcultured for five passages in a commercially available endothelial growth medium (group A), was assessed over serial passages, as compared to adherent WJ-derived cells isolated and expanded for five consecutive passages in the endothelial medium (group B).

Results

The MSC phenotype of WJ explant- and pellet-derived cells, isolated and expanded in the MSC XF medium, was proven based on the expression of CD44/CD73/CD90/CD105 surface markers and osteo-/adipo-/chondrogenic multipotent differentiation potential, which differed according to the isolation method and/or passage number. Upon exposure to endothelial differentiation cues, cells belonging to group A did not exhibit endothelial cell characteristics over serial passages; by contrast, WJ pellet-derived cells belonging to group B expressed endothelial characteristics at gene, protein and functional levels, potentially due to culture conditions favoring the isolation of other stem/progenitor cell types than MSCs, able to give rise to an endothelial progeny.

Conclusions

The use of defined, MSC XF media for isolation and expansion of human WJ-MSCs is a prerequisite for the establishment of their real endothelial differentiation capacity, as candidates for clinical therapy applications. Thus, the standardization of WJ-MSCs isolation and culture expansion techniques in defined, MSC XF media, for their accurate characterization, would be a priority in the stem cell research field.
Negri's Untimely Spinoza
Authors: Macherey Pierre
Published: July 2013

This essay celebrates the originality and influence of Antonio Negri's revolutionary interpretation of Dutch-Jewish philosopher Baruch Spinoza in his books The Savage Anomaly (1981) and Subversive Spinoza (1992). Negri produces a genuinely immanent and affirmative reading by identifying with Spinoza, emphasizing his resistance in advance to the Hegelian dialectic and his challenge to the mediating negativity characteristic of modernity. These aspects of his interpretation situate Negri close to Nietzsche, Deleuze, and Foucault. Negri offers the notion of “absolute democracy” as a practical means to grasp the linkage between ontology, ethics, and politics in Spinoza's philosophy.
Reinventing Drama with Toni Negri: Fragments from Two Working Sessions on Swarm with Barbara Nicolier
Authors: Tuaillon David
Published: July 2013

Antonio Negri's theatrical collaborators Barbara Nicolier and David Tuaillon situate Negri's recent turn to stage drama, which has so far produced the Trilogy of Resistance (Swarm, The Bent Man, and Cithaeron) and the Trilogy of Critique (The Laughing Man, Renzo the Partisan, and Prometheus), in relation to classical Greek tragedy and recent political theater (Bertolt Brecht and Heiner Müller). In a transcription of their free-form working sessions on Negri's first play, the three discuss a number of intersecting themes and methods: dreams as a source of critical or creative thought and militant organization or action, Buenaventura Durruti and the Spanish anarchists, contemporary forms of alienation and exploitation, the differences between writing Empire and writing drama, typologies of militancy, Brecht's The Measures Taken (also known as The Decision, Die Massnahme), and Müller's Mauser.
Interactions between sarco-endoplasmic reticulum and mitochondria in cardiac and skeletal muscle – pivotal roles in Ca2+ and reactive oxygen species signaling
Authors: Eisner Verónica , Csordás György , Hajnóczky György
Published: July 2013

Mitochondria are strategically and dynamically positioned in the cell to spatially coordinate ATP production with energy needs and to allow the local exchange of material with other organelles. Interactions of mitochondria with the sarco-endoplasmic reticulum (SR/ER) have been receiving much attention owing to emerging evidence on the role these sites have in cell signaling, dynamics and biosynthetic pathways. One of the most important physiological and pathophysiological paradigms for SR/ER–mitochondria interactions is in cardiac and skeletal muscle. The contractile activity of these tissues has to be matched by mitochondrial ATP generation that is achieved, at least in part, by propagation of Ca2+ signals from SR to mitochondria. However, the muscle has a highly ordered structure, providing only limited opportunity for mitochondrial dynamics and interorganellar interactions. This Commentary focuses on the latest advances in the structure, function and disease relevance of the communication between SR/ER and mitochondria in muscle. In particular, we discuss the recent demonstration of SR/ER–mitochondria tethers that are formed by multiple proteins, and local Ca2+ transfer between SR/ER and mitochondria.
Bmp2 gene in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells
Authors: Yang W. , Guo D. , Harris M.A. , Cui Y. , Gluhak-Heinrich J. , Wu J. , Chen X.-D. , Skinner C , Nyman J. , Edwards J.R. , Mundy G.R. , Lichtler A. , Kream B. , Rowe D. , Kalajzic I. , David V. , Quarles D. , Villareal D. , Scott Greg , Ray Manas , Liu S. , Martin J.F. , Mishina Y. , Harris S.E.
Published: July 2013

We generated a new Bmp2 conditional knock-out allele without a neo cassette and removed Bmp2 gene in osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in reduced bone formation rate, and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSC), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Several marker genes of MSC (α-SMA, CD146 and Angiopoietin-1), in vitro CFU assays and deletion of the Bmp2 gene in vitro in α-SMA+ BMSC support our conclusions. Critical roles of the Bmp2 gene in osteoblasts and MSC are a vital link between bone formation, vascularization and mesenchymal stem cells.
Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities
Authors: Pizzo Elio , Sarcinelli Carmen , Sheng Jinghao , Fusco Sabato , Formiggini Fabio , Netti Paolo , Yu Wenhao , D'Alessio Giuseppe , Hu Guo-fu
Published: July 2013

Angiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and is accumulated in nucleolus where it stimulates ribosomal RNA (rRNA) transcription. When cells are stressed, ANG mediates the production of tRNA-derived stress-induced small RNA (tiRNA) that reprograms protein translation into a survival mechanism. The ribonucleolytic activity of ANG is essential for both processes but how this activity is regulated is unknown. We report here that ribonuclease/angiogenin inhibitor1 (RNH1) controls both localization and activities of ANG. Under growth conditions, ANG is located in the nucleus and is not associated with RNH1 so that the ribonucleolytic activity is retained to ensure rRNA transcription, whereas cytoplasmic ANG is associated with and inhibited by RNH1 so that random cleavage of cellular RNA is prevented. Under stresses, ANG is located in cytoplasm and is concentrated in stress granules (SG) where it is not associated with RNH1 thus remains enzymatically active for tiRNA production. In contrast, nuclear ANG is associated with RNH1 in stressed cells to ensure that the enzymatic activity is inhibited and no unnecessary rRNA is produced to save anabolic energy. Knockdown of RNH1 abolished stress-induced relocalization of ANG and decreased cell growth and survival.
Application of Gas Chromatography-Quadrupole-Time-of-Flight-Mass Spectrometry for Post-Target Analysis of Volatile Compounds in Fructus Amomi
Authors: Kang Wenyu , Zhang Fang , Su Yue , Guo Yinlong
Published: July 2013

A post-target analysis method based on gas chromatography coupled to a high-resolution quadrupole time-of-flight mass analyzer is applied for the investigation of volatile compounds in Fructus Amomi. A series of narrow window extracted ion chromatograms at selected characteristic ions were performed. Chromatographic peaks with the same retention time in different extracted ion chromatograms was used to screen out the candidate compound. Identification was achieved by the accurate masses of several characteristic ions and the retention index of the peak. Forty six compounds, including 12 monoterpene compounds, were identified by conventional static headspace gas chromatography mass spectrometry and another six monoterpene compounds were found and identified by the post-target method. Post-target analysis is a useful strategy in qualitative research of natural products.
Evaluation of Relative Isotopic Abundance Measurements in a Quadrupole Time-of-Flight Mass Spectrometer for Elemental Composition Determination of Natural Products in Traditional Chinese Medicine
Authors: Wu Zhi-Jun , Huo Jia-Li , Chen Jian-Zhong , Li Na , Fang Dong-Mei , Chen Xiao-Zhen , Zhang Guo-Lin , Wang Jian-Hua , Xu Xiao-Ying
Published: July 2013

The relative isotopic abundance (RIA) measurement errors of a quadrupole time-of-flight (Q-ToF) instrument incorporating analog-to-digital converter detectors were systemically evaluated by stochastically collecting about 200 data in positive ion mass spectrometry (MS) mode. Errors varied with peak intensities at definite spectral acquisition rates but were very close, even if peak intensities changed sharply at different spectral acquisition rates with the same concentration. Intensity thresholds were systematically defined at 1 Hz of spectral acquisition rates. RIA measurement errors were also evaluated using peak area. It seemed that peak area was better adapted for the high-intensity ions while peak intensity was suited for very low-intensity ions. Several known compounds were selected for RIA measurements for product ions in tandem mass spectropmetry (MS/MS) mode. An extract of a representative traditional Chinese medicinal, Paederia scandens was analyzed with high-performance liquid chromatography-electrospray ionization-QToF-MS/MS. The unique elemental compositions of some compounds could not be identified even with exact masses and MS/MS spectra of measured and reference compounds. RIA errors, especially of (M + 2)M−1, provided vital information for determining the elemental composition.
Prevalence of antibiotic-resistant E. coli in retail chicken: comparing conventional, organic, kosher, and raised without antibiotics
Authors: Millman Jack M , Waits Kara , Grande Heidi , Marks Ann R , Marks Jane C , Price Lance B , Hungate Bruce A
Published: July 2013

Retail poultry products are known sources of antibiotic-resistant Escherichia coli, a major human health concern. Consumers have a range of choices for poultry, including conventional, organic, kosher, and raised without antibiotics (RWA)-designations that are perceived to indicate differences in quality and safety. However, whether these categories vary in the frequency of contamination with antibiotic-resistant E. coli is unknown. We examined the occurrence of antibiotic-resistant E. coli on raw chicken marketed as conventional, organic, kosher and RWA. From April – June 2012, we purchased 213 samples of raw chicken from 15 locations in the New York City metropolitan area. We screened E. coli isolates from each sample for resistance to 12 common antibiotics. Although the organic and RWA labels restrict the use of antibiotics, the frequency of antibiotic-resistant E. coli tended to be only slightly lower for RWA, and organic chicken was statistically indistinguishable from conventional products that have no restrictions. Kosher chicken had the highest frequency of antibiotic-resistant E. coli, nearly twice that of conventional products, a result that belies the historical roots of kosher as a means to ensure food safety. These results indicate that production methods influence the frequency of antibiotic-resistant E. coli on poultry products available to consumers. Future research to identify the specific practices that cause the high frequency of antibiotic-resistant E. coli in kosher chicken could promote efforts to reduce consumer exposure to this potential pathogen.
I. Embryonal vasculature formation recapitulated in transgenic mammary tumor spheroids implanted pseudo-orthotopicly into mouse dorsal skin fold: the organoblasts concept
Authors: Witkiewicz Halina , Oh Phil , Schnitzer Jan E
Published: July 2013

Inadequate understanding of cancer biology is a problem. This work focused on cellular mechanisms of tumor vascularization. According to earlier studies, the tumor vasculature derives from host endothelial cells (angiogenesis) or their precursors of bone marrow origin circulating in the blood (neo-vasculogenesis) unlike in embryos. In this study, we observed the neo-vasculature form in multiple ways from local precursor cells. Recapitulation of primitive as well as advanced embryonal stages of vasculature formation followed co-implantation of avascular (in vitro cultured) N202 breast tumor spheroids and homologous tissue grafts into mouse dorsal skin chambers. Ultrastructural and immunocytochemical analysis of tissue sections exposed the interactions between the tumor and the graft tissue stem cells. It revealed details of vasculature morphogenesis not seen before in either tumors or embryos. A gradual increase in complexity of the vascular morphogenesis at the tumor site reflected a range of steps in ontogenic evolution of the differentiating cells. Malignant- and surgical injury repair-related tissue growth prompted local cells to initiate extramedullar erythropoiesis and vascular patterning. The new findings included: interdependence between the extramedullar hematopoiesis and assembly of new vessels (both from the locally differentiating precursors); nucleo-cytoplasmic conversion (karyolysis) as the mechanism of erythroblast enucleation; the role of megakaryocytes and platelets in vascular pattern formation before emergence of endothelial cells; lineage relationships between hematopoietic and endothelial cells; the role of extracellular calmyrin in tissue morphogenesis; and calmyrite, a new ultrastructural entity associated with anaerobic energy metabolism. The central role of the extramedullar erythropoiesis in the formation of new vasculature (blood and vessels) emerged here as part of the tissue building process including the lymphatic system and nerves, and suggests a cellular mechanism for instigating variable properties of endothelial surfaces in different organs. Those findings are consistent with the organoblasts concept, previously discussed in a study on childhood tumors, and have implications for tissue definition.
Soluble Urokinase Plasminogen Activator Receptor for Risk Prediction in Patients Admitted with Acute Chest Pain
Authors: Lyngbæk Stig , Andersson Charlotte , Marott Jacob L , Møller Daniél V , Christiansen Michael , Iversen Kasper K , Clemmensen Peter , Eugen-Olsen Jesper , Hansen Peter R , Jeppesen Jørgen L
Published: July 2013

BACKGROUND

Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non–ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain.

METHODS

suPAR concentrations were measured on admission in 449 consecutive chest pain patients in a single center between January 3, 2005, and February 14, 2006. Patients were followed for all-cause mortality from discharge until July 28, 2011.

RESULTS

The diagnoses at discharge comprised high-risk NSTEACS [non–ST elevation myocardial infarction or unstable angina with electrocardiogram (ECG) abnormalities] in 77 patients (17.2%) and low-risk NSTEACS without evidence of myocardial ischemia in 257 (57.2%) of patients. Another 115 (25.6%) of patients received other diagnoses. During a median follow-up of 5.7 years (range, 0.01–6.6 years) there were 162 (36.1%) deaths. suPAR was predictive of mortality independent of age, sex, smoking, final diagnosis for the hospitalization, comorbidities (diabetes, hypertension, previous myocardial infarction, and heart failure), and variables measured on the day of admission (renal function, inflammatory markers, and markers of myocardial ischemia) with a hazard ratio (95% CI) of 1.93 (1.48–2.51) per SD increase in log-transformed suPAR, P < 0.0001. The use of suPAR improved the predictive accuracy of abnormal ECG findings and increased troponin concentrations regarding all-cause mortality (c statistics, 0.751–0.805; P < 0.0001).

CONCLUSIONS

suPAR is a strong predictor of adverse long-term outcomes and improves risk stratification beyond traditional risk variables in chest pain patients admitted with suspected NSTEACS.
Lp
boundedness of the commutators of
Marcinkiewicz integrals with rough kernels
Authors: Chen Yanping , Ding Yong
Published: July 2013

This paper is devoted to the study of the Lp
-mapping properties of the commutators

μ

Ω
;
b
,
1

${\mu _{\Omega ;b,1}}$

,

μ

Ω
,
λ
;
b
,
1

*

${ \mu _{\Omega ,\lambda ;b,1}^{*}}$

and

μ

Ω
,
S
;
b
,
1

${ \mu _{\Omega ,S;b,1}}$

, which are formed respectively by a BMO

(

ℝ
n

)

${(\mathbb {R}^n)}$

function b(x) and a class of rough Marcinkiewicz
integral operators

μ
Ω

${\mu _\Omega }$

,

μ

Ω
,
λ

*

${\mu _{\Omega ,\lambda }^{*}}$

and

μ

Ω
,
S

${\mu _{\Omega ,S}}$

related to the Littlewood–Paley g-function, the Littlewood–Paley

g
λ
*

${g_\lambda ^*}$

-function and the Lusin area integral, respectively, with the kernel condition which is different from the condition
Ω ∈ H
1(S

n-1).
Use of antidepressants for major depressive disorder in children and adolescents: clinical considerations
Authors: Picouto María Dolores , Braquehais María Dolores
Published: July 2013

Major depressive disorder (MDD) is a frequent condition among children and, especially, among adolescents. However, its clinical presentation usually differs from that of adults. It is also associated with other diagnoses and with an increased morbidity and mortality. However, MDD in this population remains underrecognized and undertreated. Antidepressants (ATDs) are chosen when psychoeducational, psychosocial and/or psychotherapeutic approaches have failed. ATDs are generally used in severe cases, and are always combined with psychological treatments. The objective of this work is to discuss the role of ATD in child and adolescent MDD. We focus on the recommendations of the most cited and updated clinical guidelines and discuss some controversial aspects with regards efficacy and safety issues that have been raised based on the information obtained from clinical trials. Finally, we offer some practical recommendations for clinicians. All these findings also pose some doubt on the hypothesis of MDD as a homogeneous phenomenon during the human life cycle.
Attention deficit hyperactivity disorder and dual disorders. Educational needs for an underdiagnosed condition
Authors: Martinez-Raga Jose , Szerman Nestor , Knecht Carlos , de Alvaro Raquel
Published: July 2013

A wide range of comorbid psychiatric disorders overlap with attention-deficit hyperactivity disorder (ADHD) across the life span. There is a robust and complex link between ADHD and substance use disorders (SUD). The aim of this report was to review the neurobiological and other vulnerability factors explaining the comorbidity of ADHD and an addictive disorder, as well as the key aspects of the assessment and diagnosis of dually diagnosed ADHD patients. A comprehensive and systematic search of relevant databases (PubMed, Embase, and PsychINFO) was conducted to identify studies published in peer-reviewed journals until July 31, 2012, with the aim of exploring the association of ADHD and SUD with postgraduate training and residency education. Across the life span, ADHD is associated with significant impairment and comorbidity. Data from epidemiological, clinical and epidemiological studies show a very solid link between ADHD and SUD. Therefore, it is very important to carefully and systematically assess for any substance use in patients with suspected ADHD coming to initial assessment, and vice versa. While there are various valid and reliable rating and screening scales, diagnosis cannot solely rely on any of the instruments available for both SUD and ADHD in adult patients with dual pathology. The most important and effective tool in the assessment of dually diagnosed patients with ADHD and SUD is a full and comprehensive clinical and psychosocial assessment. Hence, it is essential to actively incorporate training opportunities on the assessment, diagnosis, and management of adult ADHD and dually diagnosed ADHD patients during postgraduate education residency or specialist training.
Cartilaginous melanoma: case report and review of the literature
Authors: Joana Devesa Parente , Labareda Jose Manuel Pereira da Silva , Bartolo Elvira Augusta Felgueira Leonardo Fernandes , Santos Maria Fernanda Sachse Pinto Fonseca , Vale Esmeralda Maria Seco do
Published: July 2013

Malignant melanoma can present a variety of histopathological patterns. Cartilaginous change in the absence of osteogenic differentiation is extremely rare in malignant melanoma, being among the least frequent of the wide range of melanoma histologic patterns. We report a case of a 47-year-old woman with a subungual nodule on her right great toe for many years. Histopathological examination of the lesion led to a diagnosis of malignant melanoma with cartilaginous differentiation devoid of concomitant osseous areas. It would appear that this unusual form of melanoma has a predilection for acral location, particularly the subungual region. Malignant melanoma with chondroid stroma should therefore be considered in the differential diagnosis of cartilaginous lesions of the toes and fingers. Careful examination of the overlying epidermis and identification of an in situ component of melanoma may be necessary in order to establish the correct diagnosis.
Hidradenitis suppurativa: retrospective study of 20 cases
Authors: Fernandes Nurimar Conceicao , Franco Camilla Pimentel A. , Lima Cintia Maria O.
Published: July 2013

In this study, twenty cases of severe hidradenitis suppurativa are reported, mainly in non-white people and in axillary areas. Wide surgical excision has offered good results, although relapses have occurred at variable intervals in the follow-up period.
Cutaneous malakoplakia: case report and review
Authors: Afonso Joao Paulo Junqueira Magalhaes , Ando Patricia Naomi , Padilha Maria Helena Valle de Queiroz , Michalany Nilceo Schwery , Porro Adriana Maria
Published: July 2013

Malakoplakia is a rare acquired disease that can affect many systems but is more common in the urogenital tract. Cutaneous malakoplakia is even rarer. It is far more frequent in immunodeficient patients. We report a case of cutaneous malakoplakia in a kidney transplant patient who had recently stopped receiving immunosuppressive therapy to illustrate a review of the relevant recent literature.
Treatment of pityriasis versicolor with topical application of essential oil of Cymbopogon citratus (DC) Stapf - therapeutic pilot study
Authors: Carmo Egberto Santos , Pereira Fillipe de Oliveira , Cavalcante Neuza Maria , Gayoso Carla Wanderley , Lima Edeltrudes de Oliveira
Published: July 2013

BACKGROUND: Pityriasis versicolor is a fungal infection caused by Malassezia spp. that has frequent relapses. OBJECTIVES: The main objective of this research was to perform phase I and II clinical studies, using formulations containing essential oil of Cymbopogon citratus in patients with pityriasis versicolor. METHODS: Phase I study included twenty volunteers to ascertain the safety of the formulations. In phase II, 47 volunteers randomly received essential oil formulations at 1.25 μL/mL concentration, for forty days. The shampoo should be applied three times a week and the cream twice a day. A control group in phase II, consisting of 29 volunteers, received the same formulations but with 2% ketoconazole as the active ingredient. RESULTS: No significant adverse events were observed in volunteers during Phase I. In Phase II, 30 (63.83%) volunteers using essential oil and 18 (62.07%) using ketoconazole remained until the end of the study. We observed a predominance of lesions in disseminated form, with M. sympodialis detected as the predominant agent identified in cultures. After 40 days of treatment, the rate of mycological cure was 60% (p <0.05) for the group treated with essential oil of C. citratus and over 80% (p <0.05) for the group treated with ketoconazole formulations. CONCLUSIONS: Notwithstanding the safety and antifungal effects observed in this study after application of formulations containing the essential oil of C. citratus, further studies with larger populations should be performed to confirm the actual potential of these formulations in the treatment of patients with Pityriasis versicolor.
Cutaneous histoplasmosis disclosing an HIV-infection
Authors: Marques Silvio Alencar , Silvares Maria Regina Cavariani , Camargo Rosangela Maria Pires de , Marques Mariangela Esther Alencar
Published: July 2013

Histoplasmosis is a systemic mycosis endemic in extensive areas of the Americas. The authors report on an urban adult male patient with uncommon oral-cutaneous lesions proven to be histoplasmosis. Additional investigation revealed unnoticed HIV infection with CD4+ cell count of 7/mm3. The treatment was performed with amphotericin B, a 2065 mg total dose followed by itraconazole 200mg/daily plus antiretroviral therapy with apparent cure. Histoplasmosis is an AIDS-defining opportunistic disease process; therefore, its clinical diagnosis must drive full laboratory investigation looking for unnoted HIV-infection.
Desmoplastic melanoma associated with an intraepidermal lentiginous lesion: case report and literature review
Authors: Bastos Junior Cesar de Souza , Pineiro-Maceira Juan Manuel , Moraes Fernando Manuel Belles de
Published: July 2013

Desmoplastic melanoma tends to present as firm, amelanotic papules. Microscopically, it reveals a proliferation of fusiform cells in the dermis and variable collagen deposition, as well as intraepidermal melanocytic proliferation of lentiginous type in most cases. Biopsy in a 61-year-old white male patient, who had received a diagnosis of lentigo maligna on his face 10 years before, revealed a proliferation of dermal pigmented spindle cells and collagen deposition, reaching the deep reticular dermis, with a lentiginous component. Immunohistochemistry with S-100, Melan-A and WT1 showed positivity, but it was weak with HMB45. Desmoplastic melanoma associated with lentigo maligna was diagnosed. Several authors discuss whether desmoplastic melanoma represents a progression from the lentiginous component or arises "de novo". Desmoplastic melanoma represents a minority of cases of primary cutaneous melanoma (less than 4%). Identification of lentigo maligna indicates that desmoplastic melanoma should be carefully investigated.
Do you know this syndrome?
Authors: Silveira Laura Maria Andrade , Ramos Andreia Nogueira , Amaral Isadora Rosado do , Rego Vitoria Regina Pedreira de Almeida
Published: July 2013

Congenital Hypertrichosis Lanugionsa is a rare autosomal dominant genetic disorder, with fewer than 50 cases reported in the literature. It is characterized by excessive lanugo hair, sparing only the mucous membranes, palms and soles. It may be associated with other organic abnormalities and should form part of the dermatologist's current knowledge. We discuss some aspects of the syndrome in question arising from the case report of a 2-year-old female patient, black, with classic clinical presentation, with no other associated congenital abnormalities.
Scanning electron microscopy of acantholysis in pemphigus foliaceus
Authors: Almeida Jr. Hiram Larangeira de , Leitao Aline Hatzenberger , Rossi Gabriela , Rocha Nara Moreira , Silva Ricardo Marques e
Published: July 2013

We performed scanning electron microscopy of an inverted blister roof in a case of pemphigus foliaceus. The loss of intercellular adherence could be easily seen with low magnification. The acantholytic keratinocytes displayed an irregular and sometimes polygonal contour. Round cells, typically seen in light microscopy, were also observed. The examination of a blister roof allows ultrastructural documentation of the acantholytic changes.
Follicular red dots: a normal trichoscopy feature in patients with pigmentary disorders?
Authors: Pirmez Rodrigo , Pineiro-Maceira Juan , Almeida Barbara Cristina Rodrigues de , Sodre Celso Tavares
Published: July 2013

Follicular red dots have been described as a trichoscopic feature of active discoid lupus erythematosus of the scalp and its presence associated with a better prognosis. We report five patients with pigmentary disorders in whom follicular red dots were detected during scalp examination. We suggest that this pattern is probably related to the rich vasculature that naturally envelops the normal hair follicle. The possible implications of such proposition in cases of discoid lupus erythematosus and other scalp disorders are also discussed.
Inherited epidermolysis bullosa: clinical and therapeutic aspects
Authors: Boeira Vanessa Lys Simas Yamakawa , Souza Erica Sales , Rocha Bruno de Oliveira , Oliveira Pedro Dantas , Oliveira Maria de Fátima Santos Paim de , Rêgo Vitória Regina Pedreira de Almeida , Follador Ivonise
Published: July 2013

Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages.
Pityriasis versicolor: clinical-epidemiological characterization of patients in the urban area of Buerarema-BA , Brazil
Authors: Santana Juliano Oliveira , Azevedo Fernanda Luiza Andrade de , Filho Pedro Costa Campos
Published: July 2013

BACKGROUND: Pityriasis versicolor (PV) is a cutaneous pigmentation disorder caused by a lipophilic yeast of the genus Malassezia sp. It is a superficial mycosis characterized by well-defined, slightly scaly skin lesions of variable color. In Brazil, the number of reported cases is small, and there are few epidemiological studies. OBJECTIVES: to assess incidence, characteristics of the lesions, effectiveness of the Zileri's Sign procedure, and the epidemiological profile of PV in the urban area of Buerarema - Bahia. METHODS: Biological samples were collected on pre-established days at Basic Health Care Units from July to September 2010. Sample collection was followed by laboratory diagnosis using Porto's Method. RESULTS: Of the 158 patients with suspected PV participating in the study, 105 (66.5%) were positive; 72 (68.6%) were female and 33 (31.4%) were male. Sex and location of lesions showed statistically significant differences (p<0.05). The region with the highest rate of cases of PV was found to be the center of the city, with 40.9% of diagnosed cases. The most affected age group was between 10 and 19 years. There was a significant association between the results produced through Zileri's Sign and Porto's Method in relation to positive and negative results (p<0.05). CONCLUSIONS: The results showed a higher prevalence of PV among individuals at puberty. The Zileri's Sign method proved to be counterproductive, because it showed low efficacy as a method for clinical diagnosis, yielding negative results for 36 (34.3%) patients who had been diagnosed with PV through laboratory examination.
American tegumentary leishmaniasis: an uncommon clinical and histopathological presentation
Authors: Adriano Adrilena Lopes , Leal Paula Azevedo Borges , Breckenfeld Marcelle Parente , Costa Igor dos Santos , Almeida Clarisse , Sousa Antônio Renê Diógenes de
Published: July 2013

We report a case of an unusual presentation of American Tegumentary Leishmaniasis involving a male patient with a solitary lesion on the ear lobe, persisting with minimal increase for at least six months without ulceration or related symptoms. The histological sections showed epithelial atrophy and a large number of structures consistent with Leishmania sp. amastigotes within macrophages. Treatment commenced with meglumine antimoniate resulting in regression of the condition. This report is of importance given the unusual clinical manifestation and histopathological findings in this case and the fact that there was low correlation with the extended duration of the disease.
Marshall's syndrome
Authors: Fontenelle Elisa , Almeida Ana Paula Moura de , Souza Gabriela Maria Assis de Almeida
Published: July 2013

Marshall´s syndrome is a form of acquired cutis laxa without systemic involvement, which is preceded by an inflammatory dermatitis with a neutrophilic component. We report a case of a 6-year-old boy with clinical and histopathological features of this syndrome. The etiology remains unknown and there is no definitive treatment.
Polarized dermoscopy of mammary Paget disease
Authors: Crignis Giselly Silva Neto de , Abreu Luciana de , Buçard Alice Mota , Barcaui Carlos Baptista
Published: July 2013

Mammary Paget's disease is a rare intraepithelial adenocarcinoma, located on the nipple/areola complex, highly associated with breast cancer. Although the international literature emphasizes the dermatoscopic pattern of mammary Paget's disease pigmented variant, the authors describe the dermoscopic findings of classical Paget's disease and demonstrate the presence of chrysalis-like structures, criteria recently described in the literature and not yet reported in Paget's disease.
An evaluation of the treatment of parapsoriasis with phototherapy
Authors: Duarte Ida Alzira Gomes , Korkes Karen Levy , Amorim Vanessa Alice M. , Kobata Clarice , Buense Roberta , Lazzarini Rosana
Published: July 2013

Whether parapsoriasis represents an early stage of T-cell cutaneous lymphoma is still the subject of controversy. We evaluated the efficacy of phototherapy in the treatment of parapsoriasis and its relation with TCCL. Patients diagnosed with parapsoriasis and treated with phototherapy PUVA or UVB-NB were selected. Between 1 to 8 years following treatment the evolution of their disease was evaluated. In 62 patients the cure rate was 79.3% and 17.2% showed improvement of the lesions. Only two patients developed full blown T-cell cutaneous lymphoma. Phototherapy is an excellent treatment for parapsoriasis, with high cure rates, regardless of the type of phototherapy employed. Of the 62 patients under study, parapsoriasis showed no general tendency to progress to T-cell cutaneous lymphoma.
Estimated losses of plant biodiversity in the United States from historical N deposition (1985–2010)
Authors: Clark Christopher M. , Morefield Philip E. , Gilliam Frank S. , Pardo Linda H.
Published: July 2013

Although nitrogen (N) deposition is a significant threat to herbaceous plant biodiversity worldwide, it is not a new stressor for many developed regions. Only recently has it become possible to estimate historical impacts nationally for the United States. We used 26 years (1985–2010) of deposition data, with ecosystem‐specific functional responses from local field experiments and a national critical loads (CL) database, to generate scenario‐based estimates of herbaceous species loss. Here we show that, in scenarios using the low end of the CL range, N deposition exceeded critical loads over 0.38, 6.5, 13.1, 88.6, and 222.1 million ha for the Mediterranean California, North American Desert, Northwestern Forested Mountains, Great Plains, and Eastern Forest ecoregions, respectively, with corresponding species losses ranging from <1% to 30%. When we ran scenarios assuming ecosystems were less sensitive (using a common CL of 10 kg·ha−1·yr−1, and the high end of the CL range) minimal losses were estimated. The large range in projected impacts among scenarios implies uncertainty as to whether current critical loads provide protection to terrestrial plant biodiversity nationally and urge greater research in refining critical loads for U.S. ecosystems.