bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Prednisone on the Pharmacokinetics of the Integrase Inhibitor Dolutegravir
Authors: Song Ivy H. , Borland Julie , Chen Shuguang , Savina Paul , Peppercorn Amanda F. , Piscitelli Stephen 
Published: July 2013

ABSTRACT

Prednisone, a corticosteroid frequently used to treat common AIDS-related illnesses and comorbidities, has been shown to induce drug metabolism. This study was performed to determine whether prednisone coadministration affected the pharmacokinetics of dolutegravir (DTG). In this open-label, repeat-dose study, 12 healthy subjects were administered DTG at 50 mg daily alone for 5 days and then with concomitant prednisone for 10 days (prednisone at 60 mg daily for 5 days, followed by a 5-day taper). Serial blood sampling and safety assessments were performed during the trial. Pharmacokinetic parameters were determined using noncompartmental methods and geometric least-square mean ratios, and 90% confidence intervals were generated. Coadministration of DTG and 5-day high-dose prednisone with a 5-day taper had a modest effect on DTG exposure. The area under the DTG plasma concentration-time curve, maximum observed DTG concentration, and 24-hour postdose DTG concentration were increased by 11%, 6%, and 17%, respectively, on day 10 of the combination. Similar results were observed after 5 days of DTG and prednisone. Dolutegravir and prednisone coadministration was well tolerated. The changes in plasma exposures of DTG in healthy individuals as a result of prednisone dosing were not clinically significant. No dose adjustment is required for DTG coadministered with prednisone. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01425099.)
Immunoactivating Peptide P4 Augments Alveolar Macrophage Phagocytosis in Two Diverse Human Populations
Authors: Bangert Mathieu , Wright Adam K. , Rylance Jamie , Kelly Matthew J. , Wright Angela D. , Carlone George M. , Sampson Jacquelyn S. , Rajam Gowrisankar , Ades Edwin W. , Kadioglu Aras , Gordon Stephen B. 
Published: July 2013

ABSTRACT

New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of
Streptococcus pneumoniae
ex vivo
. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on
ex vivo
-derived human lung cells.
Relationship between Trough Plasma and Epithelial Lining Fluid Concentrations of Voriconazole in Lung Transplant Recipients
Authors: Heng Siow-Chin , Snell Gregory I. , Levvey Bronwyn , Keating Dominic , Westall Glen P. , Williams Trevor J. , Whitford Helen , Nation Roger L. , Slavin Monica A. , Morrissey Orla , Kong David C. M. 
Published: July 2013

ABSTRACT

Trough (predose) voriconazole concentrations in plasma and pulmonary epithelial lining fluid (ELF) of lung transplant recipients receiving oral voriconazole preemptive treatment were determined. The mean (± standard deviation [SD]) ELF/plasma ratio was 12.5 ± 6.3. A strong positive linear relationship was noted between trough plasma and ELF voriconazole concentrations (
r
2
= 0.87), suggesting the feasibility of using trough plasma voriconazole concentration as a surrogate to estimate the corresponding concentration in ELF of lung transplant recipients.
Rapid Emergence of Echinocandin Resistance in Candida glabrata Resulting in Clinical and Microbiologic Failure
Authors: Lewis James S. , Wiederhold Nathan P. , Wickes Brian L. , Patterson Thomas F. , Jorgensen James H. 
Published: July 2013

ABSTRACT

We report a case of
Candida glabrata
candidemia that developed resistance to micafungin within 8 days of initiation of therapy in a patient without previous echinocandin exposure or other known risk factors for clinical or microbiological failure. Pre- and postresistant isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed a phenylalanine deletion at codon 659 within
FKS2
.
The Equine Antimicrobial Peptide eCATH1 Is Effective against the Facultative Intracellular Pathogen Rhodococcus equi in Mice
Authors: Schlusselhuber Margot , Torelli Riccardo , Martini Cecilia , Leippe Matthias , Cattoir Vincent , Leclercq Roland , Laugier Claire , Grötzinger Joachim , Sanguinetti Maurizio , Cauchard Julien 
Published: July 2013

ABSTRACTRhodococcus equi, the causal agent of rhodococcosis, is a major pathogen of foals and is also responsible for severe infections in immunocompromised humans. Of great concern, strains resistant to currently used antibiotics have emerged. As the number of drugs that are efficientin vivois limited because of the intracellular localization of the bacterium inside macrophages, new active but cell-permeant drugs will be needed in the near future. In the present study, we evaluated, byin vitroandex vivoexperiments, the ability of the alpha-helical equine antimicrobial peptide eCATH1 to kill intracellular bacterial cells. Moreover, the therapeutic potential of the peptide was assessed in experimental rhodococcosis induced in mice, while thein vivotoxicity was evaluated by behavioral and histopathological analysis. The study revealed that eCATH1 significantly reduced the number of bacteria inside macrophages. Furthermore, the bactericidal potential of the peptide was maintainedin vivoat doses that appeared to have no visible deleterious effects for the mice even after 7 days of treatment. Indeed, daily subcutaneous injections of 1 mg/kg body weight of eCATH1 led to a significant reduction of the bacterial load in organs comparable to that obtained after treatment with 10 mg/kg body weight of rifampin. Interestingly, the combination of the peptide with rifampin showed a synergistic interaction in bothex vivoandin vivoexperiments. These results emphasize the therapeutic potential that eCATH1 represents in the treatment of rhodococcosis.
Functional Features of TonB Energy Transduction Systems of Acinetobacter baumannii
Authors: Zimbler Daniel L. , Arivett Brock A. , Beckett Amber C. , Menke Sharon M. , Actis Luis A. 
Published: July 2013

ABSTRACT

Acinetobacter baumannii
is an opportunistic pathogen that causes severe nosocomial infections. Strain ATCC 19606
T
utilizes the siderophore acinetobactin to acquire iron under iron-limiting conditions encountered in the host. Accordingly, the genome of this strain has three
tonB
genes encoding proteins for energy transduction functions needed for the active transport of nutrients, including iron, through the outer membrane. Phylogenetic analysis indicates that these
tonB
genes, which are present in the genomes of all sequenced
A. baumannii
strains, were acquired from different sources. Two of these genes occur as components of
tonB-exbB-exbD
operons and one as a monocistronic copy; all are actively transcribed in ATCC 19606
T
. The abilities of components of these TonB systems to complement the growth defect of
Escherichia coli
W3110 mutants KP1344 (
tonB
) and RA1051 (
exbBD
) under iron-chelated conditions further support the roles of these TonB systems in iron acquisition. Mutagenesis analysis of ATCC 19606
T
tonB
1
(subscripted numbers represent different copies of genes or proteins) and
tonB
2
supports this hypothesis: their inactivation results in growth defects in iron-chelated media, without affecting acinetobactin biosynthesis or the production of the acinetobactin outer membrane receptor protein BauA.
In vivo
assays using
Galleria mellonella
show that each TonB protein is involved in, but not essential for, bacterial virulence in this infection model. Furthermore, we observed that TonB
2
plays a role in the ability of bacteria to bind to fibronectin and to adhere to A549 cells by uncharacterized mechanisms. Taken together, these results indicate that
A. baumannii
ATCC 19606
T
produces three independent TonB proteins, which appear to provide the energy-transducing functions needed for iron acquisition and cellular processes that play a role in the virulence of this pathogen.
Immunosuppressive Property within the Streptococcus pneumoniae Cell Wall That Inhibits Generation of T Follicular Helper, Germinal Center, and Plasma Cell Response to a Coimmunized Heterologous Protein
Authors: Saumyaa  , Arjunaraja Swadhinya , Pujanauski Lindsey , Colino Jesus , Torres Raul M. , Snapper Clifford M. 
Published: July 2013

ABSTRACTWe previously demonstrated that intact, inactivatedStreptococcus pneumoniae(unencapsulated strain R36A) inhibits IgG responses to a number of coimmunized soluble antigens (Ags). In this study, we investigated the mechanism of this inhibition and whether other extracellular bacteria exhibited similar effects. No inhibition was observed if R36A was given 24 h before or after immunization with soluble chicken ovalbumin (cOVA), indicating that R36A acts transiently during the initiation of the immune response. Using transgenic cOVA-specific CD4+T cells, we observed that R36A had no significant effect on T-cell activation (24 h) or generation of regulatory T cells (day 7) and only a modest effect on T-cell proliferation (48 to 96 h) in response to cOVA. However, R36A mediated a significant reduction in the formation of Ag-specific splenic germinal center T follicular helper (GC Tfh) and GC B cells and antibody-secreting cells in the spleen and bone marrow in response to cOVA or cOVA conjugated to 4-hydroxy-3-nitrophenylacetyl hapten (NP-cOVA). Of note, the inhibitory effect of intact R36A on the IgG anti-cOVA response could be reproduced using R36A-derived cell walls. In contrast to R36A, neither inactivated, unencapsulated, intactNeisseria meningitidisnorStreptococcus agalactiaeinhibited the OVA-specific IgG response. These results suggest a novel immunosuppressive property within the cell wall ofStreptococcus pneumoniae.
MARKET EFFICIENCY IN G-20 COUNTRIES: THE PARADOX OF FINANCIAL CRISIS
Authors: VIEITO JOÃO PAULO , BHANU MURTHY K. V. , TRIPATHI VANITA 
Published: July 2013

This paper is amongst the first to investigate weak-form efficiency of the most developed (G-20) countries in the world. It also measures the impact of the 2007 financial crisis on the stock markets of these countries, in terms of their efficiency. Serial correlation test, ADF unit root test, Lo and MacKinlay (1988) variance ratio test, Chow and Denning (1993) RWH test and Wrights' 2000 ranks and signs based multiple variance ratio test were utilized to carry out this analysis. The entire study period was divided into a pre-crisis period (January 1, 2005 – August 8, 2007) and a during crisis period (August 9, 2007 – Deccember 31, 2011). Strong contemporaneous effects emerged across all international markets (except Saudi Arabia) as a consequence of the 2007 crisis. This may be due to increased international intra-day activity across the world markets. It was concluded that the "Samuelson dictum," which states that "while individual stocks are efficient, the market index is inefficient," seems to hold good on a global level by analogy. This is evident on the premise that, on the whole the 2007 crisis reduced return and increased volatility, even though individual markets became more efficient. The most robust result from the analysis is that most of the individual markets are weak-form efficient. Following the crisis of 2007, the methodology used indicates that on the whole, the market efficiency of individual stock markets improved.Hence, during the pre-crisis, volatility was low but heteroskedastic. However, during the period of the crisis, volatility was high but homoscedastic. The heightened volatility and low return that are a consequence of the crisis coupled with improved market efficiency, due to market vigil and control, ensure that abnormal returns and persistent arbitrage possibilities are wiped out. This appears to be a paradox of a crisis.
3D+2DTV
Authors: Scher Steven , Liu Jing , Vaish Rajan , Gunawardane Prabath , Davis James 
Published: July 2013

3D displays are increasingly popular in consumer and commercial applications. Many such displays show 3D images to viewers wearing special glasses, while showing an incomprehensible double image to viewers without glasses. We demonstrate a simple method that provides those with glasses a 3D experience, while viewers without glasses see a 2D image without artifacts.
In addition to separate left and right images in each frame, we add a third image, invisible to those with glasses. In the combined view seen by those without glasses, this cancels the right image, leaving only the left.
If the left and right images are of equal brightness, this approach results in low contrast for viewers without glasses. Allowing differential brightness between the left and right images improves 2D contrast. We observe experimentally that: (1) viewers without glasses prefer our 3D+2DTV to a standard 3DTV, (2) viewers with glasses maintain a strong 3D percept, even when one eye is significantly darker than the other, and (3) sequential-stereo display viewers with glasses experience a depth illusion caused by the Pulfrich effect, but it is small and innocuous.
Our technique is applicable to displays using either active shutter glasses or passive glasses. Our prototype uses active shutter glasses and a polarizer.
Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics
Authors: Huang Qiang , Tan Yexiong , Yin Peiyuan , Ye Guozhu , Gao Peng , Lu Xin , Wang Hongyang , Xu Guowang 
Published: July 2013

Abstract
Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and β-oxidation with reduced tricarboxylic acid cycle and Δ-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to α-fetoprotein. Cancer Res; 73(16); 4992–5002. ©2013 AACR.
Genomic Heterogeneity of Translocation Renal Cell Carcinoma
Authors: Malouf Gabriel G. , Monzon Federico A. , Couturier Jérôme , Molinié Vincent , Escudier Bernard , Camparo Philippe , Su Xiaoping , Yao Hui , Tamboli Pheroze , Lopez-Terrada Dolores , Picken Maria , Garcia Marileila , Multani Asha S. , Pathak Sen , Wood Christopher G. , Tannir Nizar M. 
Published: July 2013

Abstract
Purpose: Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.
Experimental Design: Cytogenomic analysis was conducted with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and four cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was conducted on 27 cases using pyrosequencing.
Results: tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in seven tumors (44%), followed by a 9p loss in six cases (37%). Less frequent were losses of 3p and 17p in five cases (31%) each. Patients with 17q gain were older (P = 0.0006), displayed more genetic alterations (P &lt; 0.003), and had a worse outcome (P = 0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large-scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell line–based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared with tumors from young patients (71.1% vs. 76.7%; P = 0.02).
Conclusions: Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology. Clin Cancer Res; 19(17); 4673–84. ©2013 AACR.
ARF Regulates the Stability of p16 Protein Via REGγ-Dependent Proteasome Degradation
Authors: Kobayashi Takashi , Wang Jingqiang , Al-Ahmadie Hikmat , Abate-Shen Cory 
Published: July 2013

Abstract
The cell-cycle regulatory gene INK4A-ARF (CDKN2A) has two alternative transcripts that produce entirely different proteins, namely p14ARF and p16, which have complementary functions as regulators of p53 and pRB tumor suppressor pathways, respectively. The unusual organization of INK4A-ARF has long led to speculation of a need for coordinated regulation of p14ARF and p16. We now show that p14ARF (ARF) regulates the stability of p16 protein in human cancer cell lines, as well as in mouse embryonic fibroblasts (MEFs). In particular, ARF promotes rapid degradation of p16 protein, which is mediated by the proteasome and, more specifically, by interaction of ARF with one of its subunits, REGγ. Furthermore, this ARF-dependent destabilization of p16 can be abrogated by knockdown of REGγ or by pharmacologic blockade of its nuclear export. Thus, our findings have uncovered a novel crosstalk of 2 key tumor suppressors mediated by a REGγ-dependent mechanism. The ability of ARF to control p16 stability may influence cell-cycle function.
Implications: The ability of ARF to control p16 stability may influence cell cycle function.
Visual Overview: http://mcr.aacrjournals.org/content/11/8/828/F1.large.jpg. Mol Cancer Res; 11(8); 828–33. ©2013 AACR.
Extent of Preoperative False Lumen Thrombosis Does Not Influence Long‐Term Survival in Patients With Acute Type A Aortic Dissection
Authors: Larsen Magnus , Bartnes Kristian , Tsai Thomas T. , Eagle Kim A. , Evangelista Arturo , Nienaber Christoph A. , Suzuki Toru , Fattori Rossella , Froehlich James B. , Hutchison Stuart , Sundt Thoralf M. , Januzzi James L. , Isselbacher Eric M. , Montgomery Daniel G. , Myrmel Truls 
Published: July 2013

Background
Partial thrombosis of the false lumen has been related to aortic growth, reoperations, and death in the chronic phase of type B and repaired type A aortic dissections. The impact of preoperative false lumen thrombosis has not been studied previously. We used data from a contemporary, multinational database on aortic dissections to evaluate whether different degrees of preoperative false lumen thrombosis influenced long‐term prognosis.

Methods and Results

We examined the records of 522 patients with surgically treated acute type A aortic dissections who survived to discharge between 1996 and 2011. At the preoperative imaging, 414 (79.3%) patients had patent false lumens, 84 (16.1%) had partial thrombosis of the false lumen, and 24 (4.6%) had complete thrombosis of the false lumen. The annual median (interquartile range) aortic growth rates were 0.5 (−0.3 to 2.0) mm in the aortic arch, 2.0 (0.2 to 4.0) mm in the descending thoracic aorta, and similar regardless of the degree of false lumen thrombosis. The overall 5‐year survival rate was 84.7%, and it was not influenced by false lumen thrombosis (
P
=0.86 by the log‐rank test). Independent predictors of long‐term mortality were age >70 years (hazard ratio [
HR
], 2.34; 95% confidence interval [
CI
], 1.20 to 4.56,
P
=0.012) and postoperative cerebrovascular accident, coma, and/or renal failure (
HR
, 2.62; 95%
CI
, 1.40 to 4.92,
P
=0.003).

Conclusions
Patients with acute type A aortic dissection who survive to discharge have a favorable prognosis. Preoperative false lumen thrombosis does not influence long‐term mortality, reintervention rates, or aortic growth.
Hydrophobic sol-gel finishing for textiles: Improvement by plasma pre-treatment
Authors: Montarsolo Alessio , Periolatto Monica , Zerbola Marco , Mossotti Raffaella , Ferrero Franco 
Published: July 2013

The surface of cotton (COT) and polyester (PET) fabrics was modified to create a water-repellent finishing by depositing a modified silica-based film using the sol-gel technique. TEOS (tetraethoxysilane)-based physically modified sols with 2% and 11% on weight fabric (o.w.f.) of hydrophobic additives were tested. N-propyltrimethoxysilane (C3), hexadecyltrimethoxysilane (C16) and 1H,1H,2H,2H-fluorooctyltriethoxysilane (FOS) were investigated as additives. Furthermore, a low-temperature plasma pre-treatment was used to activate the COT and PET fabric surface to improve the sol-gel coating adhesion, resistance to abrasion and fastness to washing stresses. A complete chemical/morphological (Fourier transform infrared, X-ray photoelectron spectroscopy, scanning electron microscopy) and physical characterization (abrasion and air permeability test) of treated samples was carried out. High values of θ (around 140°) on PET and COT samples were obtained with all additives used (C3, C16 and FOS) even at a low concentration (2%). Due to plasma pre-treatment, interesting water-repellent properties were achieved for PET (θ = 148°) treated with TEOS/FOS molar ratio 0.63 and for COT (θ = 140°) with TEOS/C16 molar ratio 0.63. The enhanced coating adhesion, due to plasma surface activation, was confirmed by abrasion and washing tests.