bluuebunny/crossref_metadata_2025_split huggingface dataset:
CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes
Authors: Migita Kiyoshi , Komori Atsumasa , Torigoshi Takafumi , Maeda Yumi , Izumi Yasumori , Jiuchi Yuka , Miyashita Taiichiro , Nakamura Minoru , Motokawa Satoru , Ishibashi Hiromi 
Published: May 2011

Abstract
Introduction
Interleukin (IL)-6-type cytokines exert their effects through activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an important role in rheumatoid arthritis, since JAK inhibitors have exhibited dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, we investigated the molecular effects of a small molecule JAK inhibitor, CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK kinases in rheumatoid synovitis.

Methods
Fibroblast-like synoviocytes (FLS) were isolated from RA patients and stimulated with recombinant oncostatin M (OSM). The cellular supernatants were analyzed using cytokine protein chips. IL-6 mRNA and protein expression were analyzed by real-time PCR method and ELISA, respectively. Protein phosphorylation of rheumatoid synoviocytes was assessed by Western blot using phospho-specific antibodies.

Results
OSM was found to be a potent inducer of IL-6 in FLS. OSM stimulation elicited rapid phosphorylation of STATs suggesting activation of the JAK/STAT pathway in FLS. CP690,550 pretreatment completely abrogated the OSM-induced production of IL-6, as well as OSM-induced JAK/STAT, and activation of mitogen-activated kinases (MAPKs) in FLS.

Conclusions
These findings suggest that IL-6-type cytokines contribute to rheumatoid synovitis through activation of the JAK/STAT pathway in rheumatoid synoviocytes. Inhibition of these pro-inflammatory signaling pathways by CP690,550 could be important in the treatment of RA.
Role of certain trace minerals in oxidative stress, inflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients
Authors: Guo Chih-Hung , Liu Po-Jen , Hsia Simon , Chuang Chia-Ju , Chen Pei-Chung 
Published: May 2011

Background Asthma is associated with increased inflammation, oxidative stress and abnormal immune system function. We determined the distributions of several essential trace minerals and assessed their relationships to factors that are associated with the pathophysiological status of patients with mild/moderate asthma. Methods We enrolled 25 asthmatic patients and 25 healthy subjects. We measured: blood trace minerals, zinc (Zn), copper (Cu) and selenium (Se); oxidative stress markers thiobarbituric acid reactive substances (TBARS); antioxidant enzyme activities; percentages of CD4 and CD8 lymphocyte subsets; high-sensitivity C-reactive protein (hs-CRP); and a lung function index (FEV1/FVC%). Results Compared with healthy subjects, asthmatics had lower concentrations of Zn and Se; higher Cu concentrations, and Cu/Zn and Cu/Se ratios; and lower antioxidant enzyme glutathione peroxidase (GPx), glutathione reductase (GR) and catalase activities. Significantly increased concentrations of hs-CRP, TBARS and CD4/CD8 lymphocyte ratios were also observed. Furthermore, plasma TBARS or hs-CRP concentrations were negatively associated with Se concentrations, but were positively associated with Cu/Se ratios. CD4/CD8 lymphocyte ratios were inversely correlated with Se, while it was positively correlated with Cu/Se ratio. FEV1/FVC% was also significantly correlated with Se concentrations, and Cu/Se and Cu/Zn ratios. Conclusions Abnormal distributions of these trace minerals may aggravate oxidative damage and inflammation, increased CD4/CD8 lymphocyte ratios and decreased lung function in asthma.
Your Actions Speak Louder than Words when it Comes to Patient Safety; Electrolyte Shortages; Proper Preparation of Multi-chamber Bag
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: May 2011

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
A Retrospective Analysis of Risk Factors and Therapeutic Outcomes for Clostridium difficile Infection
Authors: Netland Patrick J. , Brochardt Stephanie M. , Koo Ji M. , Lo Tze Shien , Krenz Tammy 
Published: May 2011

Purpose To determine the Clostridium difficile infection (CDI) recurrence rate at the Veterans Affairs Medical Center (VAMC) in Fargo, North Dakota, and to determine whether certain variables (eg, type of antibiotic, medication, chronic disease state, CDI symptom control) were predictive of CDI recurrence. Methods Demographic information and laboratory data from 174 adult outpatients and inpatients were collected from electronic medical records between January 1997 and September 2009. In addition, information about the duration of non-CDI antibiotic therapy and the use of proton pump inhibitors, histamine H2 blockers, corticosteroids, and immunosuppressive medications within 60 days of CDI was collected. Information regarding comorbid conditions (eg, cancer, liver or renal disease, diabetes, chronic heart failure) in patients at the time of CDI was also collected. Results Patients below the median age of 69.5 years were more likely to continue to have diarrhea after CDI treatment than patients who were older than the median age (relative risk 1.86; 95% CI, 1.06-3.26). No association was observed between previous non-CDI treatment antibiotic use, other medication use, or comorbid conditions and the recurrence of CDI. Conclusion CDI recurrence rate at VAMC was 14%. No statistically significant association could be made between recurrence of CDI and antibiotic or medication used within 60 days of infection or with chronic disease states at the time of CDI infection. Patients younger than 69.5 years were more likely to continue to have diarrhea after CDI treatment.
Impact and Determinants of Commercial Computerized Prescriber Order Entry on the Medication Administration Process
Authors: Abbass Ibrahim , Mhatre Shivani , Sansgiry Sujit S. , Tipton Joyce , Frost Craig 
Published: May 2011

Purpose The purpose of this study was to evaluate the impact of commercial computerized prescriber order entry (CPOE) on efficiency outcomes in an 864-bed community hospital. Methods A retrospective study was developed to measure medication errors and medication order turnaround time in St. Luke's Episcopal Hospital located in the Texas Medical Center. The study data were collected by stratified random sampling through a review of medication orders submitted to the pharmacy using a paper-based order system and the CPOE system. Descriptive frequencies, chi-square test, Wilcoxon matched-pairs sign rank test, and logistic regression and multiple regression analyses were conducted to examine the relationship among variables. Results Of the 1,110 total orders reviewed (563 paper-based and 547 CPOE), a total of 135 medication errors were found, with 10.5% in paper-based versus 1.6% in CPOE. The most prevalent errors in paper-based orders were inappropriate abbreviations (24.4%), incorrect doses (15.6%), occurrences of allergy (13.3%), and wrong administration frequency (9.6%). In CPOE orders, the errors were occurrences of allergy (10.4%), incorrect doses (2.2%), and drug interaction (0.7%). CPOE resulted in a 50% reduction of medication order turnaround time (median = 24 minutes CPOE vs 48 minutes paper orders). A potential medication error, unidentified prescribers within medication orders, urgency of medication order, and implementation of CPOE were the significant ( P < .05) determinants of medication order turnaround time. Conclusion The implementation of a commercial CPOE system reduced medication errors and improved medication order turnaround times.
Ceftaroline Fosamil
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: May 2011

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The May 2011 monograph topics are on roflumilast, belimumab, azilsartan medoxomil, factor XIII concentrate (human), and crizotinib. The DUE/MUE is on roflumilast.
Microstructural Characterization of an AISI D2 Tool Steel Submitted to Cryogenic Treatment
Authors: Farina Paula Fernanda da Silva , Barbosa Celso Antonio , Goldenstein Hélio 
Published: May 2011

Abstract
Recent literature has shown several papers dealing with cryogenic treatments of tool steels. Most of them see an improvement in wear resistance supposedly due to microstructural modifications that occur at cryogenic temperatures. Cryogenic treatments are supposed to modify the way secondary carbides precipitate, obtaining a finer and more homogeneous distribution. Specimens of an AISI D2 tool steel were submitted to different thermal cycles, including cryogenic treatment, and the volumetric fraction of micrometric carbides was determined. The samples were analyzed by scanning electron microscopy and the image analysis was carried out with Image J software. The present work also discusses what is understood about secondary carbides and the modifications that occur with micrometric (from the austenite-carbide field) and nanometric (from the temper of martensite) secondary carbides. No difference was found between the micrometric carbide with and without cryogenic treatment, while some indications were found that the nanometric carbides are refined and more homogeneously distributed after cryogenic treatment.
Electrochemical studies of U(VI)/U(V) in saturated Na2CO3solution at gold nanoparticles embedded CTA-modified electrode
Authors: Sharma Manoj K. , Ambolikar Arvind S. , Aggarwal Suresh K. 
Published: May 2011

AbstractGold nanoparticles (AuNPs) were prepared in the matrix of cellulose triacetate (CTA) membrane containing a liquid anion exchanger trioctylmethylammonium chloride (Aliquat-336). The AuCl4−ions were transferred in the membrane matrix by anion-exchange process, and then subsequently reduced with NaBH4to form AuNPs in the membrane. The AuNPs-embedded CTA (AuNPs-CTA) membrane was characterized by UV-visible spectroscopy, XRD and AFM. The electrochemical properties of AuNPs-CTA modified electrode were evaluated by studying redox behavior of UO22+/UO2+couple in saturated Na2CO3solution, using voltammetric techniques. In carbonate solution, the predominant species of UO22+is [UO2(CO3)3]4−, and a stable UO2(CO3)35−complex is formed by one-electron reduction of UO2(CO3)34−. Previous reports show that the UO22+/UO2+couple, which is electrochemically reversible in less complexing media, becomes electrochemically irreversible in aqueous CO32−solution. In this study, an electrocatalytic reduction of UO22+to UO2+in saturated Na2CO3solution was observed at AuNPs-CTA-modified electrode with higher current density and faster heterogeneous electron-transfer kinetics than that at bare Au electrode. The standard heterogeneous rate constant,kº, for the reduction process at AuNPs-CTA modified electrode was about 25 times higher than that of bare Au electrode. Therefore, it is concluded that AuNPs-CTA membrane has improved the interfacial electron-transfer properties of electrode, resulting in a better electrochemical response than bare Au electrode.
“I have tried to capture you …”: Rethinking the “Alma” Theme from Mahler's Sixth Symphony
Authors: Monahan Seth 
Published: May 2011

Abstract
Since the 1940s, Mahler's Sixth Symphony has been transmitted with an informal “domestic” program centered on several claims first made in Alma Mahler's Erinnerungen. In the work, she writes, Gustav meant to depict their children (in the Scherzo), himself (in the Finale), and finally her, in the first movement's swooning secondary theme. Though critics have almost universally accepted Alma's anecdote, few have seriously asked the important question of what such a portrait would be doing in Mahler's most expressly tragic symphony. In this study I offer a hermeneutic perspective on the Sixth that concedes the possible truth of Alma's anecdote but which challenges the conventional assumption that such a spousal tribute should best be understood as a one-sided testament to Mahler's newfound nuptial bliss. After examining the theme's reception history and Mahler's domestic circumstances during the symphony's composition, I explore the ways in which the first movement's sonata narrative—a protracted conflict between (and reconciliation of) its two gendered subjects—suggestively mirrors the prevailing psychodynamics of Mahler's strained marriage. At the end of the essay I propose how this revised hearing of the opening movement might prompt a reimagining of the entire Sixth as a projected or imagined “domestic tragedy,” with special focus on the intertextual links between the work's outer movements and also between the cataclysmic finale and the penitentially anguished portions of the Third Symphony's “Armer Kinder Betterlied.”
Goal-Directed Soul? Analyzing Rhythmic Teleology in African American Popular Music
Authors: Fink Robert 
Published: May 2011

Abstract
A theoretical consideration of teleology in African American popular music, focusing on the late-1960s output of Motown Records. The question of goal direction and musical value in popular music is traced back to the theoretical dispute between Leonard Meyer and Charles Keil, who stand in for the two poles of an outmoded binarism: a “classical” music defined by control of teleology and delayed gratification, and a “popular” music defined by a liberating feeling of groove in an endless present. Soul music and culture, steeped in the aspirational drive of the black middle class, falsifies this view of African American popular music. Drawing on more recent analytical work on grooves (Butler, Danielsen), a model of rhythmic teleology is developed and then tested on two seminal tracks produced by Norman Whitfield and sung by the Temptations. In both “Cloud Nine” (1968) and “Runaway Child, Running Wild” (1969), Motown's signature “four on the floor beat” functions as a rhythmic tonic. Reception study supports the proposition that Whitfield's control of rhythmic teleology, combined with socially conscious lyrics about drug use and the counterculture, represent a powerful intervention in favor of goal direction and delayed gratification at a pivotal moment for the African American middle class.
Inferring Epidemiological Parameters on the Basis of Allele Frequencies
Authors: Stadler Tanja 
Published: May 2011

Abstract
In this article, I develop a methodology for inferring the transmission rate and reproductive value of an epidemic on the basis of genotype data from a sample of infected hosts. The epidemic is modeled by a birth–death process describing the transmission dynamics in combination with an infinite-allele model describing the evolution of alleles. I provide a recursive formulation for the probability of the allele frequencies in a sample of hosts and a Bayesian framework for estimating transmission rates and reproductive values on the basis of observed allele frequencies. Using the Bayesian method, I reanalyze tuberculosis data from the United States. I estimate a net transmission rate of 0.19/year [0.13, 0.24] and a reproductive value of 1.02 [1.01, 1.04]. I demonstrate that the allele frequency probability under the birth–death model does not follow the well-known Ewens’ sampling formula that holds under Kingman's coalescent.
Genetic Variation and the Fate of Beneficial Mutations in Asexual Populations
Authors: Lang Gregory I , Botstein David , Desai Michael M 
Published: May 2011

AbstractThe fate of a newly arising beneficial mutation depends on many factors, such as the population size and the availability and fitness effects of other mutations that accumulate in the population. It has proved difficult to understand how these factors influence the trajectories of particular mutations, since experiments have primarily focused on characterizing successful clones emerging from a small number of evolving populations. Here, we present the results of a massively parallel experiment designed to measure the full spectrum of possible fates of new beneficial mutations in hundreds of experimental yeast populations, whether these mutations are ultimately successful or not. Using strains in which a particular class of beneficial mutation is detectable by fluorescence, we followed the trajectories of these beneficial mutations across 592 independent populations for 1000 generations. We find that the fitness advantage provided by individual mutations plays a surprisingly small role. Rather, underlying “background” genetic variation is quickly generated in our initially clonal populations and plays a crucial role in determining the fate of each individual beneficial mutation in the evolving population.
A Region of the Nucleosome Required for Multiple Types of Transcriptional Silencing in Saccharomyces cerevisiae
Authors: Prescott Eugenia T , Safi Alexias , Rusche Laura N 
Published: May 2011

Abstract
Extended heterochromatin domains, which are repressive to transcription and help define centromeres and telomeres, are formed through specific interactions between silencing proteins and nucleosomes. This study reveals that in Saccharomyces cerevisiae, the same nucleosomal surface is critical for the formation of multiple types of heterochromatin, but not for local repression mediated by a related transcriptional repressor. Thus, this region of the nucleosome may be generally important to long-range silencing. In S. cerevisiae, the Sir proteins perform long-range silencing, whereas the Sum1 complex acts locally to repress specific genes. A mutant form of Sum1p, Sum1-1p, achieves silencing in the absence of Sir proteins. A genetic screen identified mutations in histones H3 and H4 that disrupt Sum1-1 silencing and fall in regions of the nucleosome previously known to disrupt Sir silencing and rDNA silencing. In contrast, no mutations were identified that disrupt wild-type Sum1 repression. Mutations that disrupt silencing fall in two regions of the nucleosome, the tip of the H3 tail and a surface of the nucleosomal core (LRS domain) and the adjacent base of the H4 tail. The LRS/H4 tail region interacts with the Sir3p bromo-adjacent homology (BAH) domain to facilitate Sir silencing. By analogy, this study is consistent with the LRS/H4 tail region interacting with Orc1p, a paralog of Sir3p, to facilitate Sum1-1 silencing. Thus, the LRS/H4 tail region of the nucleosome may be relatively accessible and facilitate interactions between silencing proteins and nucleosomes to stabilize long-range silencing.
Trex2 Enables Spontaneous Sister Chromatid Exchanges Without Facilitating DNA Double-Strand Break Repair
Authors: Dumitrache Lavinia C , Hu Lingchuan , Son Mi Young , Li Han , Wesevich Austin , Scully Ralph , Stark Jeremy , Hasty Paul 
Published: May 2011

Abstract
Trex2 is a 3′ → 5′ exonuclease that removes 3′-mismatched sequences in a biochemical assay; however, its biological function remains unclear. To address biology we previously generated trex2null mouse embryonic stem (ES) cells and expressed in these cells wild-type human TREX2 cDNA (Trex2hTX2) or cDNA with a single-amino-acid change in the catalytic domain (Trex2H188A) or in the DNA-binding domain (Trex2R167A). We found the trex2null and Trex2H188A cells exhibited spontaneous broken chromosomes and trex2null cells exhibited spontaneous chromosomal rearrangements. We also found ectopically expressed human TREX2 was active at the 3′ ends of I-SceI–induced chromosomal double-strand breaks (DSBs). Therefore, we hypothesized Trex2 participates in DNA DSB repair by modifying 3′ ends. This may be especially important for ends with damaged nucleotides. Here we present data that are unexpected and prompt a new model. We found Trex2-altered cells (null, H188A, and R167A) were not hypersensitive to camptothecin, a type-1 topoisomerase inhibitor that induces DSBs at replication forks. In addition, Trex2-altered cells were not hypersensitive to γ-radiation, an agent that causes DSBs throughout the cell cycle. This observation held true even in cells compromised for one of the two major DSB repair pathways: homology-directed repair (HDR) or nonhomologous end joining (NHEJ). Trex2 deletion also enhanced repair of an I-SceI–induced DSB by both HDR and NHEJ without affecting pathway choice. Interestingly, however, trex2null cells exhibited reduced spontaneous sister chromatid exchanges (SCEs) but this was not due to a defect in HDR-mediated crossing over. Therefore, reduced spontaneous SCE could be a manifestation of the same defect that caused spontaneous broken chromosomes and spontaneous chromosomal rearrangements. These unexpected data suggest Trex2 does not enable DSB repair and prompt a new model that posits Trex2 suppresses the formation of broken chromosomes.
The Future Nephrology Workforce
Authors: Parker Mark G. , Ibrahim Tod , Shaffer Rachel , Rosner Mitchell H. , Molitoris Bruce A. 
Published: May 2011

Summary
Interest in nephrology as a career is declining and has been on the decline for nearly one decade. From 2002 to 2009, all internal medicine subspecialties except geriatric medicine increased the number of available fellowship positions. However, only two subspecialties attracted fewer United States medical graduates (USMGs) in 2009 than in 2002: geriatric medicine and nephrology. This drop occurred at a time when demand for nephrologists is increasing and when the specialty is having a harder time benefiting from the substantial contribution of international medical graduates (IMGs).
Today's USMGs possess fundamentally different career and personal goals from their teachers and mentors. Medical students report receiving minimal exposure to nephrology in clinical rotations, and they perceive that the specialty is too complex, uninteresting, and lacks professional opportunity.
Meanwhile, the demographics of kidney disease in the United States, as well as recent national health policy developments, indicate a growing need for nephrologists. Efforts to improve the educational continuum in nephrology and enhance mentorship are essential to restoring interest in nephrology for USMGs, maintaining its appeal among IMGs, and developing a workforce sufficient to meet future demand for renal care.