bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4
Authors: Semeraro Fabrizio , Ammollo Concetta T. , Morrissey James H. , Dale George L. , Friese Paul , Esmon Naomi L. , Esmon Charles T.
Published: June 2011

The release of histones from dying cells is associated with microvascular thrombosis and, because histones activate platelets, this could represent a possible pathogenic mechanism. In the present study, we assessed the influence of histones on the procoagulant potential of human platelets in platelet-rich plasma (PRP) and in purified systems. Histones dose-dependently enhanced thrombin generation in PRP in the absence of any trigger, as evaluated by calibrated automated thrombinography regardless of whether the contact phase was inhibited. Activation of coagulation required the presence of fully activatable platelets and was not ascribable to platelet tissue factor, whereas targeting polyphosphate with phosphatase reduced thrombin generation even when factor XII (FXII) was blocked or absent. In the presence of histones, purified polyphosphate was able to induce thrombin generation in plasma independently of FXII. In purified systems, histones induced platelet aggregation; P-selectin, phosphatidylserine, and FV/Va expression; and prothrombinase activity. Blocking platelet TLR2 and TLR4 with mAbs reduced the percentage of activated platelets and lowered the amount of thrombin generated in PRP. These data show that histone-activated platelets possess a procoagulant phenotype that drives plasma thrombin generation and suggest that TLR2 and TLR4 mediate the activation process.
PI: An open-source software package for validation of the SEQUEST result and visualization of mass spectrum
Authors: Qiao Yantao , Zhang Hong , Bu Dongbo , Sun Shiwei
Published: June 2011

Background

Tandem mass spectrometry (MS/MS) has emerged as the leading method for high- throughput protein identification in proteomics. Recent technological breakthroughs have dramatically increased the efficiency of MS/MS data generation. Meanwhile, sophisticated algorithms have been developed for identifying proteins from peptide MS/MS data by searching available protein sequence databases for the peptide that is most likely to have produced the observed spectrum. The popular SEQUEST algorithm relies on the cross-correlation between the experimental mass spectrum and the theoretical spectrum of a peptide. It utilizes a simplified fragmentation model that assigns a fixed and identical intensity for all major ions and fixed and lower intensity for their neutral losses. In this way, the common issues involved in predicting theoretical spectra are circumvented. In practice, however, an experimental spectrum is usually not similar to its SEQUEST -predicted theoretical one, and as a result, incorrect identifications are often generated.

Results

Better understanding of peptide fragmentation is required to produce more accurate and sensitive peptide sequencing algorithms. Here, we designed the software PI of novel and exquisite algorithms that make a good use of intensity property of a spectrum.

Conclusions

We designed the software PI with the novel and effective algorithms which made a good use of intensity property of the spectrum. Experiments have shown that PI was able to validate and improve the results of SEQUEST to a more satisfactory degree.
ATRX has a critical and conserved role in mammalian sexual differentiation
Authors: Huyhn Kim , Renfree Marilyn B , Graves Jennifer A , Pask Andrew J
Published: June 2011

Background

X-linked alpha thalassemia, mental retardation syndrome in humans is a rare recessive disorder caused by mutations in the ATRX gene. The disease is characterised by severe mental retardation, mild alpha-thalassemia, microcephaly, short stature, facial, skeletal, genital and gonadal abnormalities.

Results

We examined the expression of ATRX and ATRY during early development and gonadogenesis in two distantly related mammals: the tammar wallaby (a marsupial) and the mouse (a eutherian). This is the first examination of ATRX and ATRY in the developing mammalian gonad and fetus. ATRX and ATRY were strongly expressed in the developing male and female gonad respectively, of both species. In testes, ATRY expression was detected in the Sertoli cells, germ cells and some interstitial cells. In the developing ovaries, ATRX was initially restricted to the germ cells, but was present in the granulosa cells of mature ovaries from the primary follicle stage onwards and in the corpus luteum. ATRX mRNA expression was also examined outside the gonad in both mouse and tammar wallaby whole embryos. ATRX was detected in the developing limbs, craniofacial elements, neural tissues, tail and phallus. These sites correspond with developmental deficiencies displayed by ATR-X patients.

Conclusions

There is a complex expression pattern throughout development in both mammals, consistent with many of the observed ATR-X syndrome phenotypes in humans. The distribution of ATRX mRNA and protein in the gonads was highly conserved between the tammar and the mouse. The expression profile within the germ cells and somatic cells strikingly overlaps with that of DMRT1, suggesting a possible link between these two genes in gonadal development. Taken together, these data suggest that ATRX has a critical and conserved role in normal development of the testis and ovary in both the somatic and germ cells, and that its broad roles in early mammalian development and gonadal function have remained unchanged for over 148 million years of mammalian evolution.
Transcriptomic analysis of Clostridium thermocellumATCC 27405 cellulose fermentation
Authors: Raman Babu , McKeown Catherine K , Rodriguez Miguel , Brown Steven D , Mielenz Jonathan R
Published: June 2011

Background

The ability of Clostridium thermocellum ATCC 27405 wild-type strain to hydrolyze cellulose and ferment the degradation products directly to ethanol and other metabolic byproducts makes it an attractive candidate for consolidated bioprocessing of cellulosic biomass to biofuels. In this study, whole-genome microarrays were used to investigate the expression of C. thermocellum mRNA during growth on crystalline cellulose in controlled replicate batch fermentations.

Results

A time-series analysis of gene expression revealed changes in transcript levels of ~40% of genes (~1300 out of 3198 ORFs encoded in the genome) during transition from early-exponential to late-stationary phase. K-means clustering of genes with statistically significant changes in transcript levels identified six distinct clusters of temporal expression. Broadly, genes involved in energy production, translation, glycolysis and amino acid, nucleotide and coenzyme metabolism displayed a decreasing trend in gene expression as cells entered stationary phase. In comparison, genes involved in cell structure and motility, chemotaxis, signal transduction and transcription showed an increasing trend in gene expression. Hierarchical clustering of cellulosome-related genes highlighted temporal changes in composition of this multi-enzyme complex during batch growth on crystalline cellulose, with increased expression of several genes encoding hydrolytic enzymes involved in degradation of non-cellulosic substrates in stationary phase.

Conclusions

Overall, the results suggest that under low substrate availability, growth slows due to decreased metabolic potential and C. thermocellum alters its gene expression to (i) modulate the composition of cellulosomes that are released into the environment with an increased proportion of enzymes than can efficiently degrade plant polysaccharides other than cellulose, (ii) enhance signal transduction and chemotaxis mechanisms perhaps to sense the oligosaccharide hydrolysis products, and nutrient gradients generated through the action of cell-free cellulosomes and, (iii) increase cellular motility for potentially orienting the cells' movement towards positive environmental signals leading to nutrient sources. Such a coordinated cellular strategy would increase its chances of survival in natural ecosystems where feast and famine conditions are frequently encountered.
A large scale comparative genomic analysis reveals insertion sites for newly acquired genomic islands in bacterial genomes
Authors: Du Pengcheng , Yang Yinxue , Wang Haiying , Liu Di , Gao George F , Chen Chen
Published: June 2011

Background

Bacterial virulence enhancement and drug resistance are major threats to public health worldwide. Interestingly, newly acquired genomic islands (GIs) from horizontal transfer between different bacteria strains were found in Vibrio cholerae, Streptococcus suis, and Mycobacterium tuberculosis, which caused outbreak of epidemic diseases in recently years.

Results

Using a large-scale comparative genomic analysis of 1088 complete genomes from all available bacteria (1009) and Archaea (79), we found that newly acquired GIs are often anchored around switch sites of GC-skew (sGCS). After calculating correlations between relative genomic distances of genomic islands to sGCSs and the evolutionary distances of the genomic islands themselves, we found that newly acquired genomic islands are closer to sGCSs than the old ones, indicating that regions around sGCSs are hotspots for genomic island insertion.

Conclusions

Based on our results, we believe that genomic regions near sGCSs are hotspots for horizontal transfer of genomic islands, which may significantly affect key properties of epidemic disease-causing pathogens, such as virulence and adaption to new environments.
Extensin network formation in Vitis vinifera callus cells is an essential and causal event in rapid and H2O2-induced reduction in primary cell wall hydration
Authors: Pereira Cristina Silva , Ribeiro José ML , Vatulescu Ada D , Findlay Kim , MacDougall Alistair J , Jackson Phil AP
Published: June 2011

Background

Extensin deposition is considered important for the correct assembly and biophysical properties of primary cell walls, with consequences to plant resistance to pathogens, tissue morphology, cell adhesion and extension growth. However, evidence for a direct and causal role for the extensin network formation in changes to cell wall properties has been lacking.

Results

Hydrogen peroxide treatment of grapevine (Vitis vinifera cv. Touriga) callus cell walls was seen to induce a marked reduction in their hydration and thickness. An analysis of matrix proteins demonstrated this occurs with the insolubilisation of an abundant protein, GvP1, which displays a primary structure and post-translational modifications typical of dicotyledon extensins. The hydration of callus cell walls free from saline-soluble proteins did not change in response to H2O2, but fully regained this capacity after addition of extensin-rich saline extracts. To assay the specific contribution of GvP1 cross-linking and other wall matrix proteins to the reduction in hydration, GvP1 levels in cell walls were manipulated in vitro by binding selected fractions of extracellular proteins and their effect on wall hydration during H2O2 incubation assayed.

Conclusions

This approach allowed us to conclude that a peroxidase-mediated formation of a covalently linked network of GvP1 is essential and causal in the reduction of grapevine callus wall hydration in response to H2O2. Importantly, this approach also indicated that extensin network effects on hydration was only partially irreversible and remained sensitive to changes in matrix charge. We discuss this mechanism and the importance of these changes to primary wall properties in the light of extensin distribution in dicotyledons.
Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis
Authors: Fenollar Florence , Nicoli François , Paquet Claire , Lepidi Hubert , Cozzone Patrick , Antoine Jean-Christophe , Pouget Jean , Raoult Didier
Published: June 2011

Background

Tropheryma whipplei, the agent of Whipple's disease, causes localised infections in the absence of histological digestive involvement. Our objective is to describe T. whipplei encephalitis.

Methods

We first diagnosed a patient presenting dementia and obesity whose brain biopsy and cerebrospinal fluid specimens contained T. whipplei DNA and who responded dramatically to antibiotic treatment. We subsequently tested cerebrospinal fluid specimens and brain biopsies sent to our laboratory using T. whipplei PCR assays. PAS-staining and T. whipplei immunohistochemistry were also performed on brain biopsies. Analysis was conducted for 824 cerebrospinal fluid specimens and 16 brain biopsies.

Results

We diagnosed seven patients with T. whipplei encephalitis who demonstrated no digestive involvement. Detailed clinical histories were available for 5 of them. Regular PCR that targeted a monocopy sequence, PAS-staining and immunohistochemistry were negative; however, several highly sensitive and specific PCR assays targeting a repeated sequence were positive. Cognitive impairments and ataxia were the most common neurologic manifestations. Weight gain was paradoxically observed for 2 patients. The patients' responses to the antibiotic treatment were dramatic and included weight loss in the obese patients.

Conclusions

We describe a new clinical condition in patients with dementia and obesity or ataxia linked to T. whipplei that may be cured with antibiotics.
Validation of the Work Observation Method By Activity Timing (WOMBAT) method of conducting time-motion observations in critical care settings: an observational study
Authors: Ballermann Mark A , Shaw Nicola T , Mayes Damon C , Gibney RT Noel , Westbrook Johanna I
Published: June 2011

Background

Electronic documentation handling may facilitate information flows in health care settings to support better coordination of care among Health Care Providers (HCPs), but evidence is limited. Methods that accurately depict changes to the workflows of HCPs are needed to assess whether the introduction of a Critical Care clinical Information System (CCIS) to two Intensive Care Units (ICUs) represents a positive step for patient care. To evaluate a previously described method of quantifying amounts of time spent and interruptions encountered by HCPs working in two ICUs.

Methods

Observers used PDAs running the Work Observation Method By Activity Timing (WOMBAT) software to record the tasks performed by HCPs in advance of the introduction of a Critical Care clinical Information System (CCIS) to quantify amounts of time spent on tasks and interruptions encountered by HCPs in ICUs.

Results

We report the percentages of time spent on each task category, and the rates of interruptions observed for physicians, nurses, respiratory therapists, and unit clerks. Compared with previously published data from Australian hospital wards, interdisciplinary information sharing and communication in ICUs explain higher proportions of time spent on professional communication and documentation by nurses and physicians, as well as more frequent interruptions which are often followed by professional communication tasks.

Conclusions

Critical care workloads include requirements for timely information sharing and communication and explain the differences we observed between the two datasets. The data presented here further validate the WOMBAT method, and support plans to compare workflows before and after the introduction of electronic documentation methods in ICUs.
Optimizing the design of nanostructures for improved thermal conduction within confined spaces
Authors: Kou Jianlong , Qian Huiguo , Lu Hangjun , Liu Yang , Xu Yousheng , Wu Fengmin , Fan Jintu
Published: June 2011

Maintaining constant temperature is of particular importance to the normal operation of electronic devices. Aiming at the question, this paper proposes an optimum design of nanostructures made of high thermal conductive nanomaterials to provide outstanding heat dissipation from the confined interior (possibly nanosized) to the micro-spaces of electronic devices. The design incorporates a carbon nanocone for conducting heat from the interior to the exterior of a miniature electronic device, with the optimum diameter,D0, of the nanocone satisfying the relationship:D02(x) ∝x1/2wherexis the position along the length direction of the carbon nanocone. Branched structure made of single-walled carbon nanotubes (CNTs) are shown to be particularly suitable for the purpose. It was found that the total thermal resistance of a branched structure reaches a minimum when the diameter ratio,β*satisfies the relationship:β*=γ-0.25bN-1/k*, whereγis ratio of length,b= 0.3 to approximately 0.4 on the single-walled CNTs,b= 0.6 to approximately 0.8 on the multiwalled CNTs,k* = 2 andNis the bifurcation number (N= 2, 3, 4 ...). The findings of this research provide a blueprint in designing miniaturized electronic devices with outstanding heat dissipation.

PACS numbers: 44.10.+i, 44.05.+e, 66.70.-f, 61.48.De
Synthesis and characterisation of biologically compatible TiO2 nanoparticles
Authors: Cheyne Richard W , Smith Tim AD , Trembleau Laurent , Mclaughlin Abbie C
Published: June 2011

We describe for the first time the synthesis of biocompatible TiO2 nanoparticles containing a functional NH2 group which are easily dispersible in water. The synthesis of water dispersible TiO2 nanoparticles coated with mercaptosuccinic acid is also reported. We show that it is possible to exchange the stearic acid from pre-synthesised fatty acid-coated anatase 5-nm nanoparticles with a range of organic ligands with no change in the size or morphology. With further organic functionalisation, these nanoparticles could be used for medical imaging or to carry cytotoxic radionuclides for radioimmunotherapy where ultrasmall nanoparticles will be essential for rapid renal clearance.
Revelation of graphene-Au for direct write deposition and characterization
Authors: Bhandari Shweta , Deepa Melepurath , Joshi Amish G , Saxena Aditya P , Srivastava Avanish K
Published: June 2011

Graphene nanosheets were prepared using a modified Hummer's method, and Au-graphene nanocomposites were fabricated by in situ reduction of a gold salt. The as-produced graphene was characterized by X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, and high-resolution transmission electron microscopy (HR-TEM). In particular, the HR-TEM demonstrated the layered crystallites of graphene with fringe spacing of about 0.32 nm in individual sheets and the ultrafine facetted structure of about 20 to 50 nm of Au particles in graphene composite. Scanning helium ion microscopy (HIM) technique was employed to demonstrate direct write deposition on graphene by lettering with gaps down to 7 nm within the chamber of the microscope. Bare graphene and graphene-gold nanocomposites were further characterized in terms of their composition and optical and electrical properties.
Expression of il-23/th17 pathway in a murine model of coxsackie virus b3-induced viral myocarditis
Authors: Yang Fan , Wu Wei-Feng , Yan Yu-Luan , Pang Yu , Kong Qing , Huang Yan-Lan
Published: June 2011

Background

The IL-23/Th17 pathway is implicated in the pathogenesis of a number of chronic inflammatory and autoimmune diseases. Whether it regulates the viral myocarditis (VMC) is unknown.

Results

To examine the pathogenesis role of IL-23/Th17 axis in VMC, we used male BALB/c mice to induced VMC by Coxsackie virus B3 (CVB3) peritoneal injection. IL-23, IL-17, and signal transducer and activator of transcription 3 (STAT3) mRNA in the myocardium of VMC mice were assessed by semi-quantitative RT-PCR. IL-23 and IL-17 protein from blood serum were evaluated by ELISA. Phosphorylated-STAT3 (p-STAT3) protein expression in the myocardium was evaluated by immunohistochemical staining. Flow cytometric analysis was used to evaluate the frequencies of Th17 subsets. Isolated CD4+T cells from VMC mice were cultured with recombinant IL-23(rIL-23)in vitro. In addition, a STAT3-specific inhibitor (S3I-201) was used to test whether regulation of STAT3 could be partly responsible for Th17 diminution. Results showed that expression of IL-23, IL-17, STAT3 mRNA and protein increased in VMC mice. When purified CD4+T cells derived from VMC mice were culturedin vitrowith rIL-23, the frequency of Th17 cells was dramatically increased, accompanied by significantly enhanced production of IL-17 in the supernatants of cultured CD4+T cells. S3I-201 significantly restrained Th17 cell proliferation.

Conclusions

The IL-23/Th17 pathway axis is strongly expressed in murine VMC, identifying a novel pathway of potential significance in viral myocarditis.
Immunogenicity in mice and rhesus monkeys vaccinated with recombinant vaccinia virus expressing bivalent E7E6 fusion proteins from human papillomavirus types 16 and 18
Authors: Zhao Li , Liu Binlei , Ren Jiao , Feng Jing , Pang Zheng , Gao Jian , Zhang Hui , Tan Wenjie , Tian Houwen , Ruan Li
Published: June 2011

Background

Persistent infection with high-risk human papillomavirus (HPV) is a predominant cause of cervical cancer, and HPV16 and HPV18 occur in 50% and 20% of cervical cancer cases, respectively. The viral oncogenes E6 and E7 are constitutively expressed by HPV-associated tumour cells and can therefore be used as target antigens for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing the HPV16/18 E7E6 fusion proteins (rVVJ16/18E7E6) for use as a therapeutic vaccine for the treatment of HPV16+and HPV18+cancers.

Methods

We constructed a bivalent recombinant vaccinia virus expressing modified E7E6 fusion proteins of HPV type 16 and 18 (rVVJ16/18E7E6) based on the vaccinia virus Tiantan strain. We then defined the cellular immune responses to the virus in mice and rhesus monkeys and assessed antitumour efficacy of these responses in mice using the TC-1 tumour challenge model.

Results

Our data demonstrated that rVVJ16/18E7E6 was able to elicit varying levels of CD8+T cell immune responses and lysis of target cells in mice in response to peptides HPV16E749-57and HPV18E667-75. Furthermore, the virus was also able to induce anti-tumour responses in the HPV16+TC-1 tumour challenge model, including partial protection (30-40%) and delayed tumour appearance. In addition, the virus was able to induce immune responses in rhesus monkeys.

Conclusions

The recombinant vaccinia virus rVVJ16/18E7E6 can generate clear and significant cellular immunity in both mice and rhesus monkeys. These data provide a basis for the use of this recombinant virus as a potential vaccine candidate for further study.
Multi-locus sequence typing of Salmonella enterica subsp. enterica serovar Enteritidis strains in Japan between 1973 and 2004
Authors: Noda Tamie , Murakami Koichi , Asai Tetsuo , Etoh Yoshiki , Ishihara Tomoe , Kuroki Toshiro , Horikawa Kazumi , Fujimoto Shuji
Published: June 2011

Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) was responsible for a worldwide pandemic during the 1980s and 1990s; however, changes in the dominant lineage before and after this event remain unknown. This study determined S. Enteritidis lineages before and after this pandemic event in Japan using multilocus sequence typing (MLST). Thirty S. Enteritidis strains were collected in Japan between 1973 and 2004, consisting of 27 human strains from individual episodes, a bovine strain, a liquid egg strain and an eggshell strain. Strains showed nine phage types and 17 pulsed-field profiles with pulsed-field gel electrophoresis. All strains had homologous type 11 sequences without any nucleotide differences in seven housekeeping genes. These MLST results suggest that S. Enteritidis with the diversities revealed by phage typing and pulsed-field profiling has a highly clonal population. Although type 11 S. Enteritidis may exhibit both pleiotropic surface structure and pulsed-field type variation, it is likely to be a stable lineage derived from an ancestor before the 1980s and/or 1990s pandemic in Japan.
Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation
Authors: Echeverría Pablo C , Forafonov Fedor , Pandey Deo P , Mühlebach Guillaume , Picard Didier
Published: June 2011

Background

To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns.

Results

We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed.

Conclusions

The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses.
Magnesium concentration in amniotic fluid in the early weeks of the second trimester of pregnancy
Authors: Bocos Terraz Julia Pilar , Izquierdo Álvarez Silvia , Bancalero Flores Jose Luis , González López Ángel , Escanero Marcén Jesús Fernando
Published: June 2011

Background

We analyse magnesium levels in amniotic fluid to establish normal values for the 14th to 18th week of pregnancy and establish critical values that could be useful diagnostic and therapeutic guidelines for possible complications.

Findings

Ninety-two samples of amniotic fluid obtained by amniocentesis as well as the corresponding serum samples of pregnant women were analysed. The gestational age (mean ± SD) at which the amniotic fluid sample was obtained was 16.13 ± 1.87 weeks. Magnesium levels were determined by colorimetric assay with chlorophosphonazo-III using the the Cobas c 501 analyser (Roche Diagnostics). Statistical treatment of data was performed using the SPSS program, version 15.0.

Results revealed a mean magnesium value of 1.65 ± 0.16 mg/dL in amniotic fluid and 1.97 ± 0.23 mg/dL in serum.

Conclusions

It would be interesting to extend the study to a larger number of pregnant women to determine variations in normal magnesium values in the three trimesters of pregnancy.
FGF-23 and PTH levels in patients with acute kidney injury: A cross-sectional case series study
Authors: Zhang MaryAnn , Hsu Raymond , Hsu Chi-yuan , Kordesch Kristina , Nicasio Erica , Cortez Alfredo , McAlpine Ian , Brady Sandra , Zhuo Hanjing , Kangelaris Kirsten N , Stein John , Calfee Carolyn S , Liu Kathleen D
Published: June 2011

Background

Fibroblast growth factor-23 (FGF-23), a novel regulator of mineral metabolism, is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. However, whether FGF-23 has an analogous role in acute kidney injury is unknown. The goal of this study was to measure FGF-23 levels in critically ill patients with acute kidney injury to determine whether FGF-23 levels were elevated, as in chronic kidney disease.

Methods

Plasma FGF-23 and intact parathyroid hormone (PTH) levels were measured in 12 patients with acute kidney injury and 8 control subjects.

Results

FGF-23 levels were significantly higher in acute kidney injury cases than in critically ill subjects without acute kidney injury, with a median FGF-23 level of 1948 RU/mL (interquartile range (IQR), 437-4369) in cases compared with 252 RU/mL (IQR, 65-533) in controls (p = 0.01). No correlations were observed between FGF-23 and severity of acute kidney injury (defined by the Acute Kidney Injury Network criteria); among patients with acute kidney injury, FGF-23 levels were higher in nonsurvivors than survivors (median levels of 4446 RU/mL (IQR, 3455-5443) versus 544 RU/mL (IQR, 390-1948; p = 0.02). Severe hyperparathyroidism (defined as intact PTH >250 mg/dL) was present in 3 of 12 (25%) of the acute kidney injury subjects versus none of the subjects without acute kidney injury, although this result did not meet statistical significance.

Conclusions

We provide novel data that demonstrate that FGF-23 levels are elevated in acute kidney injury, suggesting that FGF-23 dysregulation occurs in acute kidney injury as well as chronic kidney disease. Further studies are needed to define the short- and long-term clinical effects of dysregulated mineral metabolism in acute kidney injury patients.
Early non-invasive cardiac output monitoring in hemodynamically unstable intensive care patients: A multi-center randomized controlled trial
Authors: Takala Jukka , Ruokonen Esko , Tenhunen Jyrki J , Parviainen Ilkka , Jakob Stephan M
Published: June 2011

Introduction

Acute hemodynamic instability increases morbidity and mortality. We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome.

Methods

A multicenter, randomized controlled trial was conducted in three European university hospital intensive care units in 2006 and 2007. A total of 388 hemodynamically unstable patients identified during their first six hours in the intensive care unit (ICU) were randomized to receive either non-invasive cardiac output monitoring for 24 hrs (minimally invasive cardiac output/MICO group; n = 201) or usual care (control group; n = 187). The main outcome measure was the proportion of patients achieving hemodynamic stability within six hours of starting the study.

Results

The number of hemodynamic instability criteria at baseline (MICO group mean 2.0 (SD 1.0), control group 1.8 (1.0); P = .06) and severity of illness (SAPS II score; MICO group 48 (18), control group 48 (15); P = .86)) were similar. At 6 hrs, 45 patients (22%) in the MICO group and 52 patients (28%) in the control group were hemodynamically stable (mean difference 5%; 95% confidence interval of the difference -3 to 14%; P = .24). Hemodynamic support with fluids and vasoactive drugs, and pulmonary artery catheter use (MICO group: 19%, control group: 26%; P = .11) were similar in the two groups. The median length of ICU stay was 2.0 (interquartile range 1.2 to 4.6) days in the MICO group and 2.5 (1.1 to 5.0) days in the control group (P = .38). The hospital mortality was 26% in the MICO group and 21% in the control group (P = .34).

Conclusions

Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU, nor does it alter the hemodynamic support or outcome. Our results emphasize the need to evaluate technologies used to measure stroke volume and cardiac output--especially their impact on the process of care--before any large-scale outcome studies are attempted.

Trial Registration

The study was registered at ClinicalTrials.gov (Clinical Trials identifier NCT00354211)
Visfatin Enhances CXCL8, CXCL10, and CCL20 Production in Human Keratinocytes
Authors: Kanda N. , Hau C. S. , Tada Y. , Tatsuta A. , Sato S. , Watanabe S.
Published: June 2011

Psoriasis patients are frequently associated with metabolic syndromes. Such associations are possibly mediated by adipokines. We investigated the in vitro effects of visfatin (an adipokine) on chemokine expression in human keratinocytes. Normal human keratinocytes were incubated with visfatin, and their chemokine production was analyzed by ELISA and RT-PCR. Visfatin enhanced TNF-α-induced CXC chemokine ligand (CXCL) 8, CXCL10, and CC chemokine ligand (CCL) 20 secretion and mRNA expression in keratinocytes, although visfatin alone was ineffective. A small interfering RNA against nuclear factor-κB (NF-κB) p65 suppressed the visfatin-induced production of CXCL8, CXCL10, and CCL20 whereas a small interfering RNA against signal transducer and activator of transcription (STAT) 3 suppressed CXCL8 induction. This indicates the involvement of NF-κB in CXCL8, CXCL10, and CCL20 induction by visfatin and the involvement of STAT3 in CXCL8 induction. Visfatin alone increased the transcriptional activity and tyrosine phosphorylation of STAT3, which was suppressed by Janus kinase (JAK) 2 inhibitor. Visfatin enhanced basal and TNF-α-induced NF-κB activity and inhibitory κB (IκB) α phosphorylation, which was suppressed by IκB kinase inhibitor. Visfatin induced the tyrosine and serine phosphorylation of JAK2 and IκB kinase α/β, respectively. Intraperitoneal injection of visfatin elevated mRNA and protein levels of CXCL1, CXCL10, and CCL20 in murine skin. These results suggest that visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes and homologous chemokine production in murine skin. Visfatin may induce the infiltration of type 1 or type 17 helper T cells or neutrophils to the skin via chemokine induction and thus link metabolic syndromes to psoriasis.
PWD/PhJ and WSB/EiJ Mice Are Resistant to Diet-Induced Obesity But Have Abnormal Insulin Secretion
Authors: Lee Katie T. Y. , Karunakaran Subashini , Ho Maggie M. , Clee Susanne M.
Published: June 2011

Recently, novel inbred mouse strains that are genetically distinct from the commonly used models have been developed from wild-caught mice. These wild-derived inbred strains have been included in many of the large-scale genomic projects, but their potential as models of altered obesity and diabetes susceptibility has not been assessed. We examined obesity and diabetes-related traits in response to high-fat feeding in two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), in comparison with C57BL/6J (B6). Young PWD mice displayed high fasting insulin levels, although they had normal insulin sensitivity. PWD mice subsequently developed a much milder and delayed-onset obesity compared with B6 mice but became as insulin resistant. PWD mice had a robust first-phase and increased second-phase glucose-stimulated insulin secretion in vivo, rendering them more glucose tolerant. WSB mice were remarkably resistant to diet-induced obesity and maintained very low fasting insulin throughout the study. WSB mice exhibited more rapid glucose clearance in response to an insulin challenge compared with B6 mice, consistent with their low percent body fat. Interestingly, in the absence of a measurable in vivo insulin secretion, glucose tolerance of WSB mice was better than B6 mice, likely due to their enhanced insulin sensitivity. Thus PWD and WSB are two obesity-resistant strains with unique insulin secretion phenotypes. PWD mice are an interesting model that dissociates hyperinsulinemia from obesity and insulin resistance, whereas WSB mice are a model of extraordinary resistance to a high-fat diet.
Sexing the Fetus: Feminist Politics and Method across Cultures
Authors: John Mary E.
Published: June 2011

Countries like India and China have become well known locally and internationally for their skewed girl-boy sex ratios, which have declined sharply in the very years marked by these countries' emergence as potential global economic giants. In India, these declines and the concomitant concern over the “missing” girl child have been associated with the spread of antenatal technologies such as ultrasound testing during pregnancy and their surreptitious use for sex determination and the selective abortion of female fetuses, which is banned by Indian law. This essay attempts to set up connections between Indian struggles over the problem and two U.S. feminist texts, Donna Haraway's essay “Fetus: The Virtual Speculum in the New World Order” and Rayna Rapp's ethnography Testing Women, Testing the Fetus. Many levels of disconnect across our respective “naturecultures” become visible in the process. A major argument throughout this essay is to pay closer attention to questions of method—the dominance of the language of statistics and numbers in India, for instance, compared with the ethnographic voices in Rapp's account. Rather than search for a global ethical answer to the question of the putative rights of the unborn, whether sexed or disabled, as the case may be, I argue that we need multiple modes of knowing how decisions are structured in different contexts. Only then can we acknowledge the feminist work that lies ahead in negotiating with women's diverse “choices”—as victims, criminals, and philosophically incoherent, but also as moral pioneers.
Ways of Seeing the Nation: Chinese Painting in the National Essence Journal (1905 – 1911) and Exhibition Culture
Authors: Claypool Lisa
Published: June 2011

This paper explores the uneasy position of painting in an early twentieth-century Shanghai publication, the National Essence Journal (Guocui xuebao, 1905–11), published by the prominent and influential Society for Preservation of National Learning (Guoxue baocunhui). The publication is like international expositions and museums in peculiar ways; the Chinese paintings in it, devoted to the nation, are paradoxically invisible. In the article I explore how and why, establishing the ways in which painting was newly understood to matter in the modern era.
Assuring the Safety and Effectiveness of New Drugs: Rigorous Phase IV Trials Randomizing General Practices to Delayed Access to New Drugs
Authors: Adamson Joy , Van Staa Tjeerd , Torgerson David
Published: June 2011

Randomized trials are crucial for establishing the effectiveness of new drugs and procedures. However, they are less effective at detecting uncommon but clinically significant side effects. We propose a solution. All UK general practices could be randomized to be allowed to prescribe new licenced drugs earlier or later. This would produce a large pragmatic cluster trial which could enable rare, but harmful, effects to be demonstrated more quickly than the current usual practice of looking for harmful events in observational datasets. Given current computerization of practice records such an approach is feasible and likely to be cost-effective.
Use of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia: Management of Patients and Practical Applications for Pharmacy Practitioners
Authors: Wong Siu-Fun , Mirshahidi Hamid
Published: June 2011

OBJECTIVE:

To summarize the use of tyrosine kinase inhibitors (TKIs) for treatment of patients with chronic myeloid leukemia (CML) and provide practical information for patient management.

DATA SOURCES:

Literature was retrieved from PubMed (2000-January 2011), using the search terms chronic myeloid leukemia and tyrosine kinase inhibitor. Abstracts presented at the 2008-2010 annual meetings of the American Society of Hematology and the American Society of Clinical Oncology, reference citations from identified publications, as well as the manufacturers' full prescribing information for cited drugs, also were reviewed.

STUDY SELECTION AND DATA EXTRACTION:

Articles evaluating the efficacy and safety of the TKIs imatinib, nilotinib, and dasatinib were evaluated. Focus was placed on publications supporting management of patients with CML in the chronic phase. Reports presenting clinical trial information of TKIs in development also were included.

DATA SYNTHESIS:

The discovery of targeted tyrosine kinase inhibition of BCR-ABL kinase dramatically changed the treatment of CML. Imatinib, the first TKI approved for treatment of patients with Philadelphia chromosome-positive CML, demonstrated significant superiority over the previous standard of care: interferon plus cytarabine. The newer, more potent TKIs, nilotinib and dasatinib, have demonstrated improved efficacy over imatinib as first-line therapy and provide an effective option for patients with resistance or intolerance to imatinib.

CONCLUSIONS:

To maximize efficacy of TKI therapy, close patient management, involving frequent monitoring of patient response, is essential. Given the importance of continuing TKI therapy, early recognition and management of adverse events are critical to optimizing outcomes in patients with CML. In addition to the safety profile and considerations of comorbidities, additional factors can affect therapeutic selection, including drug-drug and drug-food interactions. Research investigating new therapies, particularly for patients harboring the *** T315 mutation—which remains refractory to current TKIs—continues in the quest to improve outcomes in patients with CML.
Thioctic Acid–Induced Acute Cholestatic Hepatitis
Authors: Ridruejo Ezequiel , Castiglioni Teresa , Silva Marcelo O
Published: June 2011

Objective:

To report a case of severe cholestatic hepatitis caused by thioctic acid in a patient with diabetic peripheral polyneuropathy and mild chronic renal failure.

Case Summary:

A 63-year-old man with type 2 diabetes, hypertension, hypothyroidism, and stage 2 chronic renal failure was referred to the outpatient liver clinic with fever, asthenia, nausea, and pruritus. Because of the presence of symptomatic diabetic neuropathy, he began treatment with thioctic acid 600 mg/day. Serum transaminase levels were measured before starting thioctic acid treatment and values were within the normal range. Symptoms progressively worsened and the patient developed a low-grade fever and evidence of increased serum liver enzyme levels 45 days after starting thioctic acid treatment: aspartate aminotransferase (AST) (114 IU/L [reference range <40]), alanine aminotransferase (ALT) (191 IU/L [<35]), alkaline phosphatase (ALP) (562 IU/L [<130]), and γ-glutamyltransferase (GGT) (592 IU/L [<50]). Thioctic acid treatment was discontinued 2 days after admission. Four months after the initial presentation, his AST, ALT, and ALP levels normalized and GGT level had decreased (88 IU/L). As the patient's neuropathic symptoms worsened, thioctic acid therapy was restarted. Two months after restarting therapy, pruritus, nausea, and asthenia reappeared and the patient's liver enzyme levels became clearly abnormal again (AST 100 IU/L, ALT 129 IU/L, ALP 161 IU/L, GGT 180 IU/L). Thioctic acid was stopped, and the patient's liver enzyme levels returned to normal 2 months later.

Discussion:

Alpha-lipoic acid, also known as thioctic acid, improves metabolic glucose control and peripheral neuropathies associated with diabetes mellitus. Its administration appears to be safe and, as far as we know, there are no reports of liver toxicity associated with its use. Our patient developed acute cholestatic hepatitis after beginning treatment with thioctic acid. Use of the Roussel Uclaf causality assessment scale indicated that the association between thioctic acid treatment and our patient's drug-induced liver injury was highly probable; use of the Maria and Victorino scale indicated that the association was probable.

Conclusions:

To our knowledge, this is the first report of probable liver toxicity due to thioctic acid, a proposed “hepatoprotectant.”
Combination Loxapine and Aripiprazole for Refractory Hallucinations in Schizophrenia
Authors: Sokolski Kenneth N
Published: June 2011

Objective:

To document the effects of combining loxapine with aripiprazole for refractory hallucinations in 2 patients with chronic schizophrenia.

Case Summary:

Two patients with schizophrenia and auditory hallucinations that were unresponsive to what was considered adequate treatment with multiple typical and atypical antipsychotic medications given over several years were prescribed a combination of aripiprazole 20-30 mg and high-dose loxapine (100-300 mg/day). Both patients had refused clozapine and depot antipsychotics. Aripiprazole/loxapine therapy resolved hallucinations in both patients, and discontinuation of either medication resulted in a return of persecutory voices. Breakthrough hallucinations in both individuals responded to increasing the loxapine dosage. Adverse effects included hypersalivation and tremor, which were treated with benztropine and propranolol. The patients also reported mild sedation, which resolved after several weeks of treatment. Both patients continued to do well during 2 years after starting this combination of medications.

Discussion:

Recent research has indicated serotonergic and dopaminergic abnormalities in the superior temporal gyrus of patients with a history of chronic auditory hallucinations. Both loxapine and aripiprazole have effects on dopaminergic and postsynaptic serotonergic (5-HT2A) receptor systems, which could account for synergistic effects in treating refractory hallucinations. The combination appears safe, even when loxapine is given in high dosages. Patients should be monitored for the development of parkinsonian tremors.

Conclusions:

The combination of aripiprazole and high-dose loxapine should be considered in patients with schizophrenia who develop treatment-refractory hallucinations, particularly those who are unwilling to accept treatment with either depot antipsychotics or clozapine.
Desired properties of new phthalocyanines for photodynamic therapy
Authors: Nyokong Tebello
Published: June 2011

The manuscript focuses on the properties of phthalocyanines (Pcs) that are required for them to be employed as photosensitizers in applications such as photodynamic therapy (PDT). High triplet-state quantum yields and lifetimes as well as high singlet-oxygen quantum yields are required for a good photosensitizer. In addition, absorption of the photosensitizer in the red region of the electromagnetic spectrum is also required, and this can be achieved by ring expansion, substitution with electron-donating ligands, and change of the central metal among others. Quantum dots (QDs) are efficient accumulators of light energy, and they can transfer this energy to molecules that possess a very efficient ability to generate singlet oxygen through a process called Förster resonance energy transfer (FRET). Thus, there is a decrease in the fluorescence quantum yield of the QDs when in the vicinity of Pcs. Triplet quantum yields of the Pcs increase in the presence of QDs.
Metrological traceability of measurement results in chemistry: Concepts and implementation (IUPAC Technical Report)
Authors: De Bièvre Paul , Dybkær René , Fajgelj Aleš , Hibbert D. Brynn
Published: June 2011

This IUPAC study aims at formulating recommendations concerning the metrological traceability of a measurement result in chemistry. It is intended to provide the chemical measurement community with a consistent view of the creation, meaning, and role of metrological traceability and its underpinning concepts. No distinction is made between measurement results obtained in “high metrology” and in the “field”. A description is given of the calibration hierarchies needed in different circumstances to arrive at metrological traceability along a metrological traceability chain. Flow charts of generic calibration hierarchies are presented as well as a variety of examples. The establishment, assessment, and reporting of metrological traceability are discussed, including the provision of metrological references by a metrological institutional framework and the role of interlaboratory comparisons.