bluuebunny/crossref_metadata_2025 huggingface dataset:
Literature review regarding patient safety culture
Authors: Xuanyue Mao , Yanli Nie , Hao Cui , Pengli Jia , Mingming Zhang
Published: February 2013

Background

Quite a number of articles on patient safety culture have been published in recent 10 years to assess the safety culture in hospitals using the Hospital Survey on Patient Safety Culture in many countries. However, until now there have been no relevant studies to investigate the quality of these, and their contribution to present‐day thinking.

Objectives

The aim of this study was to explore the areas of theme, and the study design of published research on patient safety culture in literature published in English and Chinese language journals.

Methods

We searched the major databases, including MEDLINE, EMbase, Chinese Biomedical Literature Database, Chinese Journals Full‐text Database, and to analyze the publication years, research themes, authors’ affiliations and methodologies of articles published from January 2001 to December 2011. Quality and statistical method were only appraised by classification of study designs.

Results

The annual number of published articles on patient safety culture was increasing in the last decade, and the number of articles published in 2010 and 2011 reached its peak with 86 articles accounting for 44.6% of the decade's publication; patient safety culture scale dominated the included literature, accounting for 67.8% of all studies. Cross‐sectional studies and commentary reviews were the most popular study designs which took up approximately 95.9% of the included studies with 66.9% (129 articles) and 29.0% (56 articles), respectively. All the included studies on patient safety culture were conducted in the following four institutions: hospitals, geracomium, Veterans Health Administration hospitals, and medical schools.

Conclusions

There is a growing change trend in the number of articles on patient safety culture research in recent 10 years, most of which are non‐comparative studies. More methodologically rigorous designs are needed to improve research quality on patient safety culture.
ECONOMIC IMPACTS OF CULTURAL DIVERSITY IN THE NETHERLANDS: PRODUCTIVITY, UTILITY, AND SORTING*
Authors: Bakens Jessie , Mulder Peter , Nijkamp Peter
Published: February 2013

ABSTRACT This paper identifies the impact of cultural diversity on local economies, by explaining spatial disparities in wages and housing prices across Dutch cities using unique individual panel data of homeowners during the period 1999 and 2008. We distinguish between the effects of spatial sorting based on individual heterogeneity, interactions‐based productivity effects, and consumer amenities while controlling for interactions between the labor and housing market. In line with previous literature, we find a positive effect of cultural diversity on average housing prices. After controlling for spatial sorting, the effect of cultural diversity on housing prices is negative. The negative impact of cultural diversity on local housing markets is likely driven by a causal effect between the presence of immigrants and neighborhood quality that outweighs a positive effect of immigrant‐induced diversity in consumption goods.
Assessing population structure and host specialization in lichenized cyanobacteria
Authors: O'Brien Heath E. , Miadlikowska Jolanta , Lutzoni François
Published: February 2013

Coevolutionary theory predicts that the distribution of obligately symbiotic organisms will be determined by the dispersal ability and ecological range of both partners. We examined this prediction for lichen‐forming fungi that form obligate symbioses with cyanobacteria.

We compared genotypes of both partners of 250 lichens collected at multiple spatial scales in British Columbia, Canada. Multilocus sequence data collected from a subset of 128 of the specimens were used to determine the degree of recombination within the cyanobacterial populations.

We found that six distinct clusters of cyanobacterial genotypes are distributed throughout the known global phylogeny of the genus Nostoc, and that each appears to be evolving clonally. Fungal specialization is high, with each species associating with either one or two of the cyanobacterial clusters, while cyanobacterial specialization varies, with clusters associating with between one and 12 different fungal species. Specialization also varies geographically, with some combinations restricted to a single site despite the availability of both partners elsewhere.

Photobiont association patterns are determined by a combination of genetically based specificity, spatial population structure, and ecological factors and cannot be easily predicted by photobiont dispersal syndromes.
Cross‐reactive humoral responses to influenza and their implications for a universal vaccine
Authors: Chiu Christopher , Wrammert Jens , Li Gui‐Mei , McCausland Megan , Wilson Patrick C. , Ahmed Rafi
Published: February 2013

Influenza remains one of the most important causes of respiratory infection despite the widespread availability of vaccines. As effective vaccines against influenza principally rely on the induction of strain‐specific neutralizing antibodies for their protective efficacy, drifted escape mutants and genetically reassortant pandemic strains can rapidly overcome them. Several groups have recently described cross‐reactive influenza antibodies in humans, some of which bind to the conserved hemagglutinin stem. If such antibodies could be consistently induced at high levels by vaccines, they might protect against both seasonal and pandemic influenza strains. Here we discuss the humoral responses to influenza infection and vaccination, with particular reference to the pandemic H1N1 2009 virus and induction of broadly cross‐reactive stem‐binding antibodies. Having shown that cross‐reactive antibodies are preferentially induced by a pandemic hemagglutinin, the challenge is now to design a vaccine that applies these principles to the induction of heterosubtypic immunity.
Declining volatility, a general property of disparate systems: from fossils, to stocks, to the stars
Authors: Lieberman Bruce S. , Melott Adrian L.
Published: February 2013

Abstract: There may be structural principles pertaining to the general behaviour of systems that lead to similarities in a variety of different contexts. Classic examples include the descriptive power of fractals, the importance of surface area to volume constraints, the universality of entropy in systems, and mathematical rules of growth and form. Documenting such overarching principles may represent a rejoinder to the Neodarwinian synthesis that emphasizes adaptation and competition. Instead, these principles could indicate the importance of constraint and structure on form and evolution. Here, we document a potential example of a phenomenon suggesting congruent behaviour of very different systems. We focus on the notion that universally there has been a tendency for more volatile entities to disappear from systems such that the net volatility in these systems tends to decline. We specifically focus on origination and extinction rates in the marine animal fossil record, the performance of stocks in the stock market, and the characters of stars and stellar systems. We consider the evidence that each is experiencing declining volatility, and also consider the broader significance of this.
(When) Does Tit‐for‐tat Diplomacy in Trade Policy Pay Off?
Authors: Dluhosch Barbara , Horgos Daniel
Published: February 2013

In international relations, short‐run incentives for non‐cooperation often dominate. Yet, (external) institutions for enforcing cooperation are hampered by national sovereignty, supposedly strengthening the role of self‐enforcing mechanisms. This paper examines their scope with a focus on contingent protection aka tit‐for‐tat in trade policy. Highlighting various strategies in a partial equilibrium framework, we show that retaliation of non‐cooperative behaviour by limiting market access works as a disciplining device quite independently of supply and demand parameters. Our empirical findings are consistent with the theoretical results in that countries more frequently involved in WTO‐mediated disputes entailing tit‐for‐tat strategies pursue on average more liberal trade regimes.
Effects of 2 MeV Ge+ irradiation on AlGaN/GaN high electron mobility transistors
Authors: Douglas Erica A. , Bielejec Edward , Frenzer Patrick , Yates Bradley R. , Pearton Stephen J. , Lo Chien-Fong , Liu Lu , Kang Tsung-Sheng , Ren Fan
Published: February 2013

The dc characteristics of AlGaN/GaN high electron mobility transistors (HEMTs) were measured before and after irradiation with 2 MeV Ge+ ions at doses from 5 × 1010 to 5 × 1012 cm−2. The drain current, gate leakage current, and transconductance decreased monotonically with dose, while the drain-source resistance increased to a much greater extent than observed previously for proton irradiation of similar devices. The data are consistent with a strong decrease in electron concentration in the HEMT channel. During off-state electrical stressing of AlGaN/GaN HEMTs, the typical critical voltage for unirradiated devices was ∼13 V. By sharp contrast, no critical voltage was detected for proton irradiated HEMTs up to 35 V, indicating that the Ge irradiation had a strong influence on the electric field distribution near the gate electrode.
TRIPpin’ on a Fat Cell
Authors: Baker Aaron B.
Published: February 2013

A newly discovered role for the transcription coregulator TRIP-Br2 may provide a target for preventing and treating obesity.
Running Interference on Tumor Growth
Authors: Bettegowda Chetan
Published: February 2013

A new clinical trial using siRNA to treat patients with liver tumors demonstrates safety and early signs of efficacy.
Novel Benzoxazole Inhibitor of Dengue Virus Replication That Targets the NS3 Helicase
Authors: Byrd Chelsea M. , Grosenbach Douglas W. , Berhanu Aklile , Dai Dongcheng , Jones Kevin F. , Cardwell Kara B. , Schneider Christine , Yang Guang , Tyavanagimatt Shanthakumar , Harver Chris , Wineinger Kristin A. , Page Jessica , Stavale Eric , Stone Melialani A. , Fuller Kathleen P. , Lovejoy Candace , Leeds Janet M. , Hruby Dennis E. , Jordan Robert
Published: February 2013

Dengue virus (DENV) is the predominant mosquito-borne viral pathogen that infects humans with an estimated 50 to 100 million infections per year worldwide. Over the past 50 years, the incidence of dengue disease has increased dramatically and the virus is now endemic in more than 100 countries. Moreover, multiple serotypes of DENV are now found in the same geographic region, increasing the likelihood of more severe forms of disease. Despite extensive research, there are still no approved vaccines or therapeutics commercially available to treat DENV infection. Here we report the results of a high-throughput screen of a chemical compound library using a whole-virus assay that identified a novel small-molecule inhibitor of DENV, ST-610, that potently and selectively inhibits all four serotypes of DENV replication
in vitro
. Sequence analysis of drug-resistant virus isolates has identified a single point mutation, A263T, in the NS3 helicase domain that confers resistance to this compound. ST-610 inhibits DENV NS3 helicase RNA unwinding activity in a molecular-beacon-based helicase assay but does not inhibit nucleoside triphosphatase activity based on a malachite green ATPase assay. ST-610 is nonmutagenic, is well tolerated (nontoxic) in mice, and has shown efficacy in a sublethal murine model of DENV infection with the ability to significantly reduce viremia and viral load compared to vehicle controls.
Activities of Systemically Administered Echinocandins against
In Vivo
Mature Candida albicans Biofilms Developed in a Rat Subcutaneous Model
Authors: Kucharíková Soňa , Sharma Nidhi , Spriet Isabel , Maertens Johan , Van Dijck Patrick , Lagrou Katrien
Published: February 2013

This study addresses the effects of micafungin, caspofungin, and anidulafungin against
Candida albicans
biofilms developed in a subcutaneous catheter rat model system. Doses of 5, 10, and 30 mg/kg (of body weight)/day (the last only for micafungin) were given intravenously for 5, 7, and 10 days. All three echinocandins caused a significant reduction of the
Candida
cell numbers on the implanted catheters and are thus promising for the treatment of biofilm-related infections.
Persistence of Resistant Variants in Hepatitis C Virus-Infected Patients Treated with the NS5A Replication Complex Inhibitor Daclatasvir
Authors: Wang Chunfu , Sun Jin-Hua , O'Boyle Donald R. , Nower Peter , Valera Lourdes , Roberts Susan , Fridell Robert A. , Gao Min
Published: February 2013

Daclatasvir (DCV; BMS-790052) is a hepatitis C virus (HCV) NS5A replication complex inhibitor (RCI) with picomolar to low nanomolar potency and broad genotypic coverage
in vitro
. Viral RNA declines have been observed in the clinic for both alpha interferon-ribavirin (IFN-α–RBV) and IFN-RBV-free regimens that include DCV. Follow-up specimens (up to 6 months) from selected subjects treated with DCV in 14-day monotherapy studies were analyzed for genotype and phenotype. Variants were detected by clonal sequencing in specimens from baseline and were readily detected by population sequencing following viral RNA breakthrough and posttreatment. The major amino acid substitutions generating resistance
in vivo
were at residues M28, Q30, L31, and Y93 for genotype 1a (GT-1a) and L31 and Y93 for GT-1b, similar to the resistance substitutions observed with the
in vitro
replicon system. The primary difference in the resistance patterns observed
in vitro
and
in vivo
was the increased complexity of linked variant combinations observed in clinical specimens. Changes in the percentage of individual variants were observed during follow-up; however, the overall percentage of variants in the total population persisted up to 6 months. Our results suggest that during the 14-day monotherapy, most wild-type virus was eradicated by DCV. After the end of DCV treatment, viral fitness, rather than DCV resistance, probably determines which viral variants emerge as dominant in populations.
Bis-(3′-5′)-Cyclic Dimeric GMP Regulates Antimicrobial Peptide Resistance in Pseudomonas aeruginosa
Authors: Chua Song Lin , Tan Sean Yang-Yi , Rybtke Morten Theil , Chen Yicai , Rice Scott A. , Kjelleberg Staffan , Tolker-Nielsen Tim , Yang Liang , Givskov Michael
Published: February 2013

Bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger that controls the lifestyles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes a planktonic lifestyle. Here, we used the expression of different reporters to show that planktonic cells, biofilm cells, and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced the expression of proteins required for the virulence and development of antimicrobial peptide resistance in
Pseudomonas aeruginosa
. In accordance with this,
P. aeruginosa
cells with low c-di-GMP levels were found to be more resistant to colistin than
P. aeruginosa
cells with high c-di-GMP levels. This finding contradicts the current dogma stating that dispersed cells are inevitably more susceptible to antibiotics than their sessile counterparts.
Natural History of Yersinia pestis Pneumonia in Aerosol-Challenged BALB/c Mice
Authors: Heine Henry S. , Chuvala Lara , Riggins Renaldo , Hurteau Gregory , Cirz Ryan , Cass Robert , Louie Arnold , Drusano G. L.
Published: February 2013

After a relatively short untreated interval, pneumonic plague has a mortality approaching 100%. We employed a murine model of aerosol challenge with
Yersinia pestis
to investigate the early course of pneumonic plague in the lung, blood, and spleen. We fit a mathematical model to all data simultaneously. The model fit to the data was acceptable. The number of organisms in the lung at baseline was estimated to be 135 (median) or 1,184 (mean) CFU/g. The doubling time was estimated as 1.5 to 1.7 h. Between 1 and 12 h postexposure, counts declined, but they then increased by 24 h, a finding hypothesized to be due to innate immunity. The model predicted that innate immunity declined with a half-time of 3 to 3.8 h. The threshold for bacteremia was 6.4 × 10
4
to 1.52 × 10
6
CFU/g. By 42 to 48 h, stationary phase was obtained. Lung bacterial burdens exceeded 10 log CFU/g. Obviating early defenses allows for rapid amplification of
Y. pestis
in bacteremia, making the rapid course with high mortality understandable.
Inflammasome Components Coordinate Autophagy and Pyroptosis as Macrophage Responses to Infection
Authors: Byrne Brenda G. , Dubuisson Jean-Francois , Joshi Amrita D. , Persson Jenny J. , Swanson Michele S.
Published: February 2013

When microbes contaminate the macrophage cytoplasm, leukocytes undergo a proinflammatory death that is initiated by nucleotide-binding-domain-, leucine-rich-repeat-containing proteins (NLR proteins) that bind and activate caspase-1. We report that these inflammasome components also regulate autophagy, a vesicular pathway to eliminate cytosolic debris. In response to infection with flagellate
Legionella pneumophila
, C57BL/6J mouse macrophages equipped with caspase-1 and the NLR proteins NAIP5 and NLRC4 stimulated autophagosome turnover. A second trigger of inflammasome assembly, K
+
efflux, also rapidly activated autophagy in macrophages that produced caspase-1. Autophagy protects infected macrophages from pyroptosis, since caspase-1-dependent cell death occurred more frequently when autophagy was dampened pharmacologically by either 3-methyladenine or an inhibitor of the Atg4 protease. Accordingly, in addition to coordinating pyroptosis, both (pro-) caspase-1 protein and NLR components of inflammasomes equip macrophages to recruit autophagy, a disposal pathway that raises the threshold of contaminants necessary to trigger proinflammatory leukocyte death.

IMPORTANCE
An exciting development in the innate-immunity field is the recognition that macrophages enlist autophagy to protect their cytoplasm from infection. Nutrient deprivation has long been known to induce autophagy; how infection triggers this disposal pathway is an active area of research. Autophagy is encountered by many of the intracellular pathogens that are known to trigger pyroptosis, an inflammatory cell death initiated when nucleotide-binding-domain-, leucine-rich-repeat-containing proteins (NLR proteins) activate caspase-1 within inflammasome complexes. Therefore, we tested the hypothesis that NLR proteins and caspase-1 also coordinate autophagy as a barrier to cytosolic infection. By exploiting classical bacterial and mouse genetics and kinetic assays of autophagy, we demonstrate for the first time that, when confronted with cytosolic contamination, primary mouse macrophages rely not only on the NLR proteins NAIP5 and NLRC4 but also on (pro-)caspase-1 protein to mount a rapid autophagic response that wards off proinflammatory cell death.
A Decade of Plague in Mahajanga, Madagascar: Insights into the Global Maritime Spread of Pandemic Plague
Authors: Vogler Amy J. , Chan Fabien , Nottingham Roxanne , Andersen Genevieve , Drees Kevin , Beckstrom-Sternberg Stephen M. , Wagner David M. , Chanteau Suzanne , Keim Paul
Published: February 2013

A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62 years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (SNP) discovery on those strains, screened the discovered SNPs, and performed a high-resolution 43-locus multilocus variable-number tandem-repeat analysis of the isolate panel. Twenty-two new SNPs were identified and defined a new phylogenetic lineage among the Malagasy isolates. Phylogeographic analysis suggests that the Mahajanga lineage likely originated in the Ambositra district in the highlands, spread throughout the northern central highlands, and was then introduced into and became transiently established in Mahajanga. Although multiple transfers between the central highlands and Mahajanga occurred, there was a locally differentiating and dominant subpopulation that was primarily responsible for the 1991-to-1999 Mahajanga outbreaks. Phylotemporal analysis of this Mahajanga subpopulation revealed a cycling pattern of diversity generation and loss that occurred during and after each outbreak. This pattern is consistent with severe interseasonal genetic bottlenecks along with large seasonal population expansions. The ultimate extinction of plague pathogens in Mahajanga suggests that, in this environment, the plague pathogen niche is tenuous at best. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments.

IMPORTANCE
Maritime spread of plague led to the global dissemination of this disease and affected the course of human history. Multiple historical plague waves resulted in massive human mortalities in three classical plague pandemics: Justinian (6th and 7th centuries), Middle Ages (14th to 17th centuries), and third (mid-1800s to the present). Key to these events was the pathogen’s entry into new lands by “plague ships” via seaport cities. Although initial disease outbreaks in ports were common, they were almost never sustained for long and plague pathogens survived only if they could become established in ecologically suitable habitats. Although plague pathogens’ ability to invade port cities has been essential for intercontinental spread, these regions have not proven to be a suitable long-term niche. The disease dynamics in port cities such as Mahajanga are thus critical to plague pathogen amplification and dispersal into new suitable ecological niches for the observed global long-term maintenance of plague pathogens.
Kdo Hydrolase Is Required for Francisella tularensis Virulence and Evasion of TLR2-Mediated Innate Immunity
Authors: Okan Nihal A. , Chalabaev Sabina , Kim Tae-Hyun , Fink Avner , Ross Robin A. , Kasper Dennis L.
Published: February 2013

The highly virulent
Francisella tularensis
subsp.
tularensis
has been classified as a category A bioterrorism agent. A live vaccine strain (LVS) has been developed but remains unlicensed in the United States because of an incomplete understanding of its attenuation. Lipopolysaccharide (LPS) modification is a common strategy employed by bacterial pathogens to avoid innate immunity. A novel modification enzyme has recently been identified in
F. tularensis
and
Helicobacter pylori
. This enzyme, a two-component Kdo (3-deoxy-
d
-manno-octulosonic acid) hydrolase, catalyzes the removal of a side chain Kdo sugar from LPS precursors. The biological significance of this modification has not yet been studied. To address the role of the two-component Kdo hydrolase KdhAB in
F. tularensis
pathogenesis, a Δ
kdhAB
deletion mutant was constructed from the LVS strain. In intranasal infection of mice, the Δ
kdhAB
mutant strain had a 50% lethal dose (LD
50
) 2 log
10
units higher than that of the parental LVS strain. The levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid were significantly higher (2-fold) in mice infected with the Δ
kdhAB
mutant than in mice infected with LVS.
In vitro
stimulation of bone marrow-derived macrophages with the Δ
kdhAB
mutant induced higher levels of TNF-α and IL-1β in a TLR2-dependent manner. In addition, TLR2
−/−
mice were more susceptible than wild-type mice to Δ
kdhAB
bacterial infection. Finally, immunization of mice with Δ
kdhAB
bacteria elicited a high level of protection against the highly virulent
F. tularensis
subsp.
tularensis
strain Schu S4. These findings suggest an important role for the
Francisella
Kdo hydrolase system in virulence and offer a novel mutant as a candidate vaccine.

IMPORTANCE
The first line of defense against a bacterial pathogen is innate immunity, which slows the progress of infection and allows time for adaptive immunity to develop. Some bacterial pathogens, such as
Francisella tularensis
, suppress the early innate immune response, killing the host before adaptive immunity can mature. To avoid an innate immune response,
F. tularensis
enzymatically modifies its lipopolysaccharide (LPS). A novel LPS modification—Kdo (3-deoxy-
d
-manno-octulosonic acid) saccharide removal—has recently been reported in
F. tularensis
. We found that the ∆
kdhAB
mutant was significantly attenuated in mice. Additionally, the mutant strain induced an early innate immune response in mice both
in vitro
and
in vivo
. Immunization of mice with this mutant provided protection against the highly virulent
F. tularensis
strain Schu S4. Thus, our study has identified a novel LPS modification important for microbial virulence. A mutant lacking this modification may be used as a live attenuated vaccine against tularemia.
The heat shock response: A case study of chromatin dynamics in gene regulation
Authors: Teves Sheila S. , Henikoff Steven
Published: February 2013

Recent studies in transcriptional regulation using the Drosophila heat shock response system have elucidated many of the dynamic regulatory processes that govern transcriptional activation and repression. The classic view that the control of gene expression occurs at the point of RNA polymerase II (Pol II) recruitment is now giving way to a more complex outlook of gene regulation. Promoter chromatin dynamics coordinate with transcription factor binding to maintain the promoters of active genes accessible. For a large number of genes, the rate-limiting step in Pol II progression occurs during its initial elongation, where Pol II transcribes 30–50 bp and pauses for further signals. These paused genes have unique genic chromatin architecture and dynamics compared with genes where Pol II recruitment is rate limiting for expression. Further elongation of Pol II along the gene causes nucleosome turnover, a continuous process of eviction and replacement, which suggests a potential mechanism for Pol II transit along a nucleosomal template. In this review, we highlight recent insights into transcription regulation of the heat shock response and discuss how the dynamic regulatory processes involved at each transcriptional stage help to generate faithful yet highly responsive gene expression.
Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis
Authors: Winnick J. J. , Ramnanan C. J. , Saraswathi V. , Roop J. , Scott M. , Jacobson P. , Jung P. , Basu R. , Cherrington A. D. , Edgerton D. S.
Published: February 2013

The aim of this study was to determine the effect of prolonged 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibition on basal and hormone-stimulated glucose metabolism in fasted conscious dogs. For 7 days prior to study, either an 11β-HSD1 inhibitor (HSD1-I; n = 6) or placebo (PBO; n = 6) was administered. After the basal period, a 4-h metabolic challenge followed, where glucagon (3×-basal), epinephrine (5×-basal), and insulin (2×-basal) concentrations were increased. Hepatic glucose fluxes did not differ between groups during the basal period. In response to the metabolic challenge, hepatic glucose production was stimulated in PBO, resulting in hyperglycemia such that exogenous glucose was required in HSD-I ( P < 0.05) to match the glycemia between groups. Net hepatic glucose output and endogenous glucose production were decreased by 11β-HSD1 inhibition ( P < 0.05) due to a reduction in net hepatic glycogenolysis ( P < 0.05), with no effect on gluconeogenic flux compared with PBO. In addition, glucose utilization ( P < 0.05) and the suppression of lipolysis were increased ( P < 0.05) in HSD-I compared with PBO. These data suggest that inhibition of 11β-HSD1 may be of therapeutic value in the treatment of diseases characterized by insulin resistance and excessive hepatic glucose production.
Breast cancer resistance protein regulates apical ectoplasmic specialization dynamics stage specifically in the rat testis
Authors: Qian Xiaojing , Mruk Dolores D. , Wong Elissa W. P. , Cheng C. Yan
Published: February 2013

Drug transporters determine the bioavailability of drugs in the testis behind the blood-testis barrier (BTB). Thus, they are crucial for male contraceptive development if these drugs (e.g., adjudin) exert their effects behind the BTB. Herein breast cancer resistance protein (Bcrp), an efflux drug transporter, was found to be expressed by both Sertoli and germ cells. Interestingly, Bcrp was not a component of the Sertoli cell BTB. Instead, it was highly expressed by peritubular myoid cells at the tunica propria and also endothelial cells of the microvessels in the interstitium at all stages of the epithelial cycle. Unexpectedly, Bcrp was found to be expressed at the Sertoli-step 18–19 spermatid interface but limited to stage VI-early VIII tubules, and an integrated component of the apical ectoplasmic specialization (apical ES). Apparently, Bcrp is being used by late-stage spermatids to safeguard their completion of spermiogenesis by preventing harmful drugs to enter these cells while they transform to spermatozoa. Also, the association of Bcrp with actin, Eps8 (epidermal growth factor receptor pathway substrate 8, an actin barbed end capping and bundling protein), and Arp3 (actin-related protein 3, a component of the Arp2/3 complex known to induce branched actin polymerization) at the apical ES suggest that Bcrp may be involved in regulating the organization of actin filament bundles at the site. Indeed, a knockdown of Bcrp by RNAi in the testis perturbed the apical ES function, disrupting spermatid polarity and adhesion. In summary, Bcrp is a regulator of the F-actin-rich apical ES in the testis.
MiRNA-200b represses transforming growth factor-β1-induced EMT and fibronectin expression in kidney proximal tubular cells
Authors: Tang Owen , Chen Xin-Ming , Shen Sylvie , Hahn Michael , Pollock Carol A.
Published: February 2013

MicroRNAs (miRNAs) comprise of a novel class of endogenous small noncoding RNAs that frequently downregulate the expression of target genes. Recent reports suggest that miRNA-200b prevents epithelial-to-mesenchymal transition (EMT) in cancer cells by targeting the E-box binding transcription factors Zinc finger E-box-binding homeobox 1 (ZEB1) and Zinc finger E-box-binding homeobox 2 (ZEB2). About 35% of active fibroblasts are derived from EMT which is central to the development of progressive renal fibrosis. Hence, this study was designed to assess the effect of miRNA-200b on transforming growth factor-β (TGF-β1)-induced fibrotic responses in renal tubular cells. Morphologically, human kidney-2 cells transfected with miRNA-200b retained their epithelial cell characteristics when exposed to TGF-β1. miRNA-200b significantly increased E-cadherin ( P < 0.001) and reduced fibronectin mRNA and protein expression (both P < 0.01) independent of phospho-Smad2/3 and phospho-p38 and p42/44 signaling. Increased E-cadherin expression was associated with decreased expression of ZEB1 and ZEB2 and repression of fibronectin was mediated through direct targeting of the fibronectin mRNA, demonstrated using pMIR luciferase reporter assay and site-directed mutagenesis. These results suggest that miRNA-200b suppresses TGF-β1-induced EMT via inhibition of ZEB1 and ZEB2 and the extracellular matrix protein fibronectin by directing targeting of its 3′UTR mRNA, independent of pathways directly involved in TGF-β1 signaling.
Proximal tubule-specific overexpression of netrin-1 suppresses acute kidney injury-induced interstitial fibrosis and glomerulosclerosis through suppression of IL-6/STAT3 signaling
Authors: Ranganathan Punithavathi , Jayakumar Calpurnia , Ramesh Ganesan
Published: February 2013

Acute kidney injury-induced organ fibrosis is recognized as a major risk factor for the development of chronic kidney disease, which remains one of the leading causes of death in the developed world. However, knowledge on molecules that may suppress the fibrogenic response after injury is lacking. In ischemic models of acute kidney injury, we demonstrate a new function of netrin-1 in regulating interstitial fibrosis. Acute injury was promptly followed by a rise in serum creatinine in both wild-type and netrin-1 transgenic animals. However, the wild-type showed a slow recovery of kidney function compared with netrin-1 transgenic animals and reached baseline by 3 wk. Histological examination showed increased infiltration of interstitial macrophages, extensive fibrosis, reduction of capillary density, and glomerulosclerosis. Collagen IV and α-smooth muscle actin expression was absent in sham-operated kidneys; however, their expression was significantly increased at 2 wk and peaked at 3 wk after reperfusion. These changes were reduced in the transgenic mouse kidney, which overexpresses netrin-1 in proximal tubular epithelial cells. Fibrosis was associated with increased expression of IL-6 and extensive and chronic activation of STAT3. Administration of IL-6 exacerbated fibrosis in vivo in wild-type, but not in netrin-1 transgenic mice kidney and increased collagen I expression and STAT3 activation in vitro in renal epithelial cells subjected to hypoxia-reoxygenation, which was suppressed by netrin-1. Our data suggest that proximal tubular epithelial cells may play a prominent role in interstitial fibrosis and that netrin-1 could be a useful therapeutic agent for treating kidney fibrosis.
Undifferentiated Spindle-Cell Carcinoma of the Gallbladder: A Report of a Case, an Immunohistochemistry Profile, and a Review of the Literature
Authors: Badmos Kabir Bolarinwa , Salah Seada Laila , Fahad Al Rashid Fawaz , Oreiby Hanan Abdulhafez
Published: February 2013

Undifferentiated spindle-cell carcinoma is a rare gallbladder cancer with a worse or similar prognosis to the generally dismal outcome seen in most gallbladder cancer patients. We reported a case of SpCC, stage IV disease that was initially diagnosed as undifferentiated pleomorphic sarcoma, but deeper sections revealed few clusters of epithelioid clear cells. Although the tumour showed biphasic appearances on haematoxylin and eosin, it exhibited poor protein expression with most sarcoma markers being negative except for focal vimentin positivity. The CEA and CK7 were positive only in the epithelioid clear cell clusters while CD 68 positive was also focally positive in the spindle-cell component. The poor tumour differentiation coupled with advanced stage at presentation was partly responsible for the disease progression and patients' death one year after surgery. Early diagnosis and surgical intervention with better understanding of this tumour biology may offer improved prognosis and survival in this rare cancer.
An Asymptotic Formula for r-Bell Numbers with Real Arguments
Authors: Corcino Cristina B. , Corcino Roberto B.
Published: February 2013

The r-Bell numbers are generalized using the concept of the Hankel contour. Some properties parallel to those of the ordinary Bell numbers are established. Moreover, an asymptotic approximation for r-Bell numbers with real arguments is obtained.
Tailoring the Spectra of White Organic Light-Emitting Devices by Trap Effect of a Concentration-Insensitive Dopant
Authors: Wang Qi , Yu Junsheng , Li Ming , Lu Zhiyun
Published: February 2013

Highly efficient phosphorescent organic light-emitting devices (PhOLEDs) had been fabricated by using a novel iridium complex, bis[2-(3′,5′-di-tert-butylbiphenyl-4-yl)benzothiazolato-N,C2′]iridium(III) (acetylacetonate) [(tbpbt)2Ir(acac)], as the emitter. With a wide doping ratio ranging from 15 wt% to 25 wt%, the PhOLEDs maintained a comparable high performance, indicating concentration-insensitive property of the (tbpbt)2Ir(acac). On the basis of the unique characteristic of concentration insensitivity, the application of this phosphor was explored by fabricating white organic light-emitting devices (WOLEDs) with altered doping ratio, indicating that trap effect of (tbpbt)2Ir(acac) could effectively tailor WOLEDs spectra. Typically, a high-power efficiency, current efficiency, and external quantum efficiency of 30.0 lm/W, 38.8 cd/A, 18.1%, were achieved by 20 wt% doped WOLEDs.
Colony Development and Density-Dependent Processes in Breeding Grey Herons
Authors: Shirai Takeshi
Published: February 2013

The density-dependent processes that limit the colony size of colonially breeding birds such as herons and egrets remain unclear, because it is difficult to monitor colonies from the first year of their establishment, and the most previous studies have considered mixed-species colonies. In the present study, single-species colonies of the Grey Heron (Ardea cinerea) were observed from the first year of their establishment for 16 years in suburban Tokyo. Colony size increased after establishment, illustrating a saturation curve. The breeding duration (days from nest building to fledging by a pair) increased, but the number of fledglings per nest decreased, with colony size. The reproductive season in each year began earlier, and there was greater variation in the timing of individual breeding when the colony size was larger. The prolonged duration until nestling feeding by early breeders of the colony suggests that herons at the beginning of the new breeding season exist in an unsteady state with one another, likely owing to interactions with immigrant individuals. Such density-dependent interference may affect reproductive success and limit the colony size of Grey Herons.
Hypercalcemia in Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review
Authors: Asao Keiko , McHugh Jonathan B. , Miller David C. , Esfandiari Nazanene H.
Published: February 2013

Objective. We here report a patient with upper urinary tract urothelial carcinoma with hypercalcemia likely due to elevated 1,25-dihydroxyvitamin D.Methods. We present a clinical case and a summary of literature search.Results. A 57-year-old man, recently diagnosed with a left renal mass, for which a core biopsy showed renal cell carcinoma, was admitted for hypercalcemia of 11.0 mg/mL He also had five small right lung nodules with a negative bone scan. Both intact parathyroid hormone and parathyroid hormone-related peptide were appropriately low, and 1,25-dihydroxyvitamin D was elevated at 118 pg/dL. The patient’s calcium was normalized after hydration, and he underwent radical nephrectomy. On the postoperative day 6, a repeat 1,25-dihydroxyvitamin D was 24 pg/mL with a calcium of 8.1 mg/dL. Pathology showed a 6 cm high-grade urothelial carcinoma with divergent differentiation. We identified a total of 27 previously reported cases with hypercalcemia and upper tract urothelial carcinoma in English. No cases have a documented elevated 1,25-dihydroxyvitamin D level.Conclusion. This clinical course suggests that hypercalcemia in this case is from the patient’s tumor, which was likely producing 1,25-dihydroxyvitamin D. Considering the therapeutic implications, hypercalcemia in patients with upper urinary tract urothelial carcinoma should be evaluated with 1,25-dihydroxyvitamin D.
Delayed Asthmatic Response to Allergen Challenge and Cytokines Released by Nonspecifically Stimulated Blood Cells
Authors: Pelikan Zdenek
Published: February 2013

Background. Bronchial asthma patients can develop various asthmatic response types following bronchial allergen challenge, such as immediate (IAR), late (LAR), dual late (DLAR), or delayed (DYAR), due to different immunologic mechanisms. The DYAR, recorded in 24 patients, beginning between 26 and 32 hrs and lasting up to 56 hrs after the bronchial allergen challenge, differs from the IAR, LAR, and DLAR in clinical, diagnostic, and immunologic aspects.Objective. To investigate amounts of particular cytokines released by the blood cells after an additional nonspecific stimulation with Phorbol 12-myristate 13-acetate (PMA) during the DYAR.Methods. In 24 patients, the repeated DYAR was supplemented with determination of cytokines both in the nonstimulated plasma and in the supernatants of the blood cells stimulated with PMA before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay.Results. No significant changes of the prechallenge cytokine concentrations in the non-stimulated serum were recorded in the DYAR patients as compared with the healthy subjects. The DYAR was accompanied by significantly increased postchallenge concentrations (P<0.05) of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, G-CSF, TNF-α, and TGF-β, while decreased concentration of IL-7 (P<0.05) in the nonstimulated plasma. The significantly increased postchallenge concentrations of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, TNF-α, and TGF-βwere released by peripheral blood cells after stimulation with PMA, as compared with both their prechallenge concentrations and with the PBS control values.Conclusions. These results would support evidence for an important role of the Th1 cells, neutrophils, monocytes, and probably also NK cells in the immunologic mechanism(s) leading to the development of the clinical DYAR. Nevertheless, an additional role of macrophages, endothelial and epithelial cells in these mechanisms cannot be even excluded.
Global Patterns of Prostate Cancer Incidence, Aggressiveness, and Mortality in Men of African Descent
Authors: Rebbeck Timothy R. , Devesa Susan S. , Chang Bao-Li , Bunker Clareann H. , Cheng Iona , Cooney Kathleen , Eeles Rosalind , Fernandez Pedro , Giri Veda N. , Gueye Serigne M. , Haiman Christopher A. , Henderson Brian E. , Heyns Chris F. , Hu Jennifer J. , Ingles Sue Ann , Isaacs William , Jalloh Mohamed , John Esther M. , Kibel Adam S. , Kidd LaCreis R. , Layne Penelope , Leach Robin J. , Neslund-Dudas Christine , Okobia Michael N. , Ostrander Elaine A. , Park Jong Y. , Patrick Alan L. , Phelan Catherine M. , Ragin Camille , Roberts Robin A. , Rybicki Benjamin A. , Stanford Janet L. , Strom Sara , Thompson Ian M. , Witte John , Xu Jianfeng , Yeboah Edward , Hsing Ann W. , Zeigler-Johnson Charnita M.
Published: February 2013

Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world.
A Generalized Learning Curve Adapted for Purchasing and Cost Reduction Negotiations
Authors: Wong Lam F.
Published: February 2013

This paper presents the use and validation of a generalized learning curve in the economies of scale purchasing experience. The model, based on Wright’s curve, incorporates two extra degrees of freedom to accommodate initial purchases of multiple (instead of single) units and a finite asymptotic price at high volumes. The study shows that each time the part purchase quantity is doubled, the price is reduced either by a constant percentage (a learning rate) or by an approach to an asymptotic plateau rate indicating a point of diminishing returns. Supplier price quotations at multiple purchase quantities were obtained for a pool of 17 critical parts. The data were fitted with the generalized learning curve by the method of least squares regression. The regressed learning rate, first unit price, and the asymptotic price can be used to infer supplier pricing strategies. Coupled with a “should-cost” analysis based on estimates of standard time and material, a system cost reduction task was carried out by the supply chain organization.
Analytic Hierarchy Process Expansion for Innovation Performance Measurement Framework
Authors: Kim Song-Kyoo
Published: February 2013

Innovation is a top strategic priority for the majority of companies. The need for innovation becomes more and more evident in the current corporate world, and the purpose of innovation is to create business value. The Analytic Hierarchy Process (AHP) is a structured technique for organizing and analyzing complex decisions. This paper is targeting the framework design of the innovation performance criteria and provides the general guidelines to evaluate the relationship between the criteria by using AHP expansion.
The Relationship between Thermal Comfort and Light Intensity with Sleep Quality and Eye Tiredness in Shift Work Nurses
Authors: Azmoon Hiva , Dehghan Habibollah , Akbari Jafar , Souri Shiva
Published: February 2013

Environmental conditions such as lighting and thermal comfort are influencing factors on sleep quality and visual tiredness. The purpose of this study was the determination of the relationship between thermal comfort and light intensity with the sleep quality and eye fatigue in shift nurses.Method.This cross-sectional research was conducted on 82 shift-work personnel of 18 nursing workstations in Isfahan Al-Zahra Hospital, Iran, in 2012. Heat stress monitoring (WBGT) and photometer (Hagner Model) were used for measuring the thermal conditions and illumination intensity, respectively. To measure the sleep quality, visual tiredness, and thermal comfort, Pittsburg sleep quality index, eye fatigue questionnaire, and thermal comfort questionnaire were used, respectively. The data were analyzed with descriptive statistics, Student'st-test, and Pearson correlation.Results.Correlation between thermal comfort which was perceived from the self-reporting of people with eye tiredness was −0.38 (P=0.002). Pearson correlation between thermal comfort and sleep quality showed a positive and direct relationship (r=0.241,P=0.33) but the correlation between thermal comfort, which was perceived from the self-reporting of shift nurses, and WBGT index was a weak relationship (r=0.019).Conclusion.Based on the obtained findings, it can be concluded that a defect in environmental conditions such as thermal conditions and light intensity and also lack of appropriate managerial plan for night shift-work nurses are destructive and negative factors for the physical and mental health of this group of practitioners.