bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Virological Efficacy after Switch to Once-Daily Lopinavir-Ritonavir in Treatment-Experienced HIV-1-Infected Children
Authors: Foissac Frantz , Urien Saïk , Hirt Déborah , Frange Pierre , Chaix Marie-Laure , Treluyer Jean-Marc , Blanche Stéphane 
Published: July 2011

ABSTRACTLopinavir-ritonavir (LPV/r) is a protease inhibitor that is used twice daily (BID) in the treatment of HIV infection in children. In the context of a single-center observational study, a switch to a once-a-day (QD) LPV/r regimen was proposed for considerations of convenience and to support adherence. The aims of this study were to compare the pharmacokinetics, viral loads, percentages of CD4+T cells, and lipid profiles after switching from a twice-daily to a once-daily regimen of LPV/r in experienced children. For this purpose, LPV concentrations, viral loads, CD4+T cells, and biochemistry data were measured in routine therapeutic drug monitoring procedures in 45 children and adolescents. Thirty-six children were switched to the QD regimen. Nine children on the BID or QD regimen were added for pharmacokinetic-study purposes only. The QD trough concentrations (Ctrough) of lopinavir in plasma were significantly lower than those observed with the BID regimen (P< 0.0001), but the 24-h exposure levels were not significantly lower with the QD than with the BID regimen (P= 0.09). Among 34 evaluable patients who switched from the BID to the QD regimen, the virological efficacy of LPV/r appeared to differ (P< 0.001), with 74% and 57% of viral loads, respectively, being <50 copies/ml (mean follow-up times, 33 and 20 months). Among 22 patients with stable virological control before the switch, 12 experienced either failure or blip (one observation of detectable viral load between two observations of undetectable viral load) after the switch. The change from the BID to the QD regimen did not result in significant differences in CD4+T cell percentages or total cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels. The switch from the BID to the QD LPV/r regimen led to equivalent exposure and lowerCtroughvalues and resulted in lower levels of virological control in these antiretroviral-experienced children.
Superoxide Dismutases Are Involved in Candida albicans Biofilm Persistence against Miconazole
Authors: Bink Anna , Vandenbosch Davy , Coenye Tom , Nelis Hans , Cammue Bruno P. A. , Thevissen Karin 
Published: July 2011

ABSTRACT

We investigated the cellular mechanisms responsible for the occurrence of miconazole-tolerant persisters in
Candida albicans
biofilms. Miconazole induced about 30% killing of sessile
C. albicans
cells at 75 μM. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2%. Since miconazole induces reactive oxygen species (ROS) in sessile
C. albicans
cells, we focused on a role for superoxide dismutases (Sods) in persistence and found the expression of Sod-encoding genes in sessile
C. albicans
cells induced by miconazole compared to the expression levels in untreated sessile
C. albicans
cells. Moreover, addition of the superoxide dismutase inhibitor
N
,
N
′-diethyldithiocarbamate (DDC) to
C. albicans
biofilms resulted in an 18-fold reduction of the miconazole-tolerant persister fraction and in increased endogenous ROS levels in these cells. Treatment of biofilms of
C. albicans
clinical isolates with DDC resulted in an 18-fold to more than 200-fold reduction of their miconazole-tolerant persister fraction. To further confirm the important role for Sods in
C. albicans
biofilm persistence, we used a Δ
sod4
Δ
sod5
mutant lacking Sods 4 and 5. Biofilms of the Δ
sod4
Δ
sod5
mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels compared to biofilms of the isogenic wild type (WT). In conclusion, the occurrence of miconazole-tolerant persisters in
C. albicans
biofilms is linked to the ROS-detoxifying activity of Sods. Moreover, Sod inhibitors can be used to potentiate the activity of miconazole against
C. albicans
biofilms.
Multicenter Evaluation of a New DNA Microarray for Rapid Detection of Clinically Relevant
bla
Genes from β-Lactam-Resistant Gram-Negative Bacteria
Authors: Bogaerts Pierre , Hujer Andrea M. , Naas Thierry , de Castro Roberta Rezende , Endimiani Andrea , Nordmann Patrice , Glupczynski Youri , Bonomo Robert A. 
Published: July 2011

ABSTRACT

A new commercial low-density microarray which identifies common extended-spectrum β-lactamase plasmid-mediated cephalosporinase genes, as well as carbapenemase (
bla
KPC
and
bla
NDM
) genes, was evaluated. We tested 207 clinical and reference/collection isolates of the
Enterobacteriaceae
possessing different
bla
genes. Overall, the sensitivity and specificity of the microarray were 100% for the detection of the plasmid-mediated
bla
AmpC
,
bla
KPC
, and
bla
NDM
genes using
bla
gene sequencing as the reference method.
In Vitro
Antibacterial Activity of NB-003 against Propionibacterium acnes
Authors: Pannu J. , McCarthy A. , Martin A. , Hamouda T. , Ciotti S. , Ma L. , Sutcliffe J. , Baker J. R. 
Published: July 2011

ABSTRACT

NB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections.
In vitro
susceptibility of
Propionibacterium acnes
to NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against all
P. acnes
isolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC
90
s/minimum bactericidal concentrations (MBC
90
s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 μg/ml, respectively. In the presence of 50% sebum, the MIC
90
s/MBC
90
s of NB003 and BPOs increased to 128/1,024 and 400/1,600 μg/ml, respectively. The MIC
90
s/MBC
90
s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC
90
s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC
90
s/MBC
90
s of 128/256 μg/ml for NB003 and 214/428 μg/ml for BPO. The addition of EDTA enhanced the
in vitro
efficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16- and >256-fold decrease in MIC
90
and MBC
90
, yielding a more potent MIC
90
/MBC
90
of ≤1/<1 μg/ml. The kinetics of bactericidal activity of NB-003 against
P. acnes
were compared to those of a commercially available product of BPO. Electron micrographs of
P. acnes
treated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance of
P. acnes
revealed no stably resistant mutant strains.
A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives
Authors: Burger-Kentischer Anke , Finkelmeier Doris , Keller Petra , Bauer Jörg , Eickhoff Holger , Kleymann Gerald , Abu Rayyan Walid , Singh Anurag , Schröppel Klaus , Lemuth Karin , Wiesmüller Karl-Heinz , Rupp Steffen 
Published: July 2011

ABSTRACT

Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (
S
)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (
S
)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic
Candida
yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules.
Targeted Disruption of Nonribosomal Peptide Synthetase
pes3
Augments the Virulence of Aspergillus fumigatus
Authors: O'Hanlon Karen A. , Cairns Timothy , Stack Deirdre , Schrettl Markus , Bignell Elaine M. , Kavanagh Kevin , Miggin Sinéad M. , O'Keeffe Grainne , Larsen Thomas O. , Doyle Sean 
Published: July 2011

ABSTRACT

Nonribosomal peptide synthesis (NRPS) is a documented virulence factor for the opportunistic pathogen
Aspergillus fumigatus
and other fungi. Secreted or intracellularly located NRP products include the toxic molecule gliotoxin and the iron-chelating siderophores triacetylfusarinine C and ferricrocin. No structural or immunologically relevant NRP products have been identified in the organism. We investigated the function of the largest gene in
A. fumigatus
, which encodes the NRP synthetase Pes3 (AFUA_5G12730), by targeted gene deletion and extensive phenotypic analysis. It was observed that in contrast to other NRP synthetases, deletion of
pes3
significantly increases the virulence of
A. fumigatus
, whereby the
pes3
deletion strain (
A. fumigatus
Δpes3
) exhibited heightened virulence (increased killing) in invertebrate (
P
< 0.001) and increased fungal burden (
P
= 0.008) in a corticosteroid model of murine pulmonary aspergillosis. Complementation restored the wild-type phenotype in the invertebrate model. Deletion of
pes3
also resulted in increased susceptibility to the antifungal, voriconazole (
P
< 0.01), shorter germlings, and significantly reduced surface β-glucan (
P
= 0.0325). Extensive metabolite profiling revealed that Pes3 does not produce a secreted or intracellularly stored NRP in
A. fumigatus
. Macrophage infections and histological analysis of infected murine tissue indicate that
Δpes3
heightened virulence appears to be mediated by aberrant innate immune recognition of the fungus. Proteome alterations in
A. fumigatus
Δ
pes3
strongly suggest impaired germination capacity. Uniquely, our data strongly indicate a structural role for the Pes3-encoded NRP, a finding that appears to be novel for an NRP synthetase.
The Neogene drainage history of south-central Idaho
Authors: Link Paul K. , Hodges Mary K.V. 
Published: July 2011

Abstract
Study of the distribution of the age-populations of detrital zircons in the Snake River system suggest that specific stream systems can be identified based on the detrital-zircon age-population signature (“barcode”) of ancient and Holocene sand deposits. Detrital zircon studies can be used on regional and local scales to determine changes in drainage patterns using both surface and subsurface data.
Regional study of drainage patterns using detrital zircons found in Neogene strata of Idaho and southwest Montana suggest northeastward late Miocene to Holocene migration of the Continental Divide from the western side of the Pioneer Mountains to the current position in southwest Montana. Specifically, mixed populations of recycled Proterozoic detrital zircons that define the Wood River drainage are not found in the western Snake River Plain until after 7 Ma. Late Miocene eastward drainage from the central Snake River Plain to southwest Montana is suggested by 9–12 Ma detrital zircons found in fluvial strata less than 6 million years old, of the Sixmile Creek Formation
Basalt eruptions of the Eastern Snake River Plain during the Pliocene and Pleistocene also caused drainage diversion. Detrital zircons in Pliocene sands from coreholes at Wendell and Mountain Home Air Force Base contain Big Lost River zircon provenance, suggesting that during the Pliocene, the Big Lost River flowed west along the central Snake River Plain.
Late Pliocene and early Pleistocene basaltic volcanoes and rhyolite dome eruptions resulted in volcanic highlands, the Axial Volcanic Zone of the eastern Snake River Plain and the northwest-trending Arco Volcanic Rift Zone (which includes Craters of the Moon volcanic center). The development of these volcanic highlands disrupted the ancestral drainage of the Pliocene Big Lost River system, confining it to the Big Lost Trough, a volcanically dammed basin of internal drainage on the Idaho National Laboratory.
After the Big Lost Trough was cut off from the main Snake River, basalt eruptions, local subsidence, and climate controlled the courses of the rivers that flowed into it. Detrital-zircon populations in core samples reveal the provenance of specific sand beds from the Big or Little Lost River systems.
Middle Cryogenian (“Sturtian”) Pocatello Formation
Authors: Keeley Joshua A. , Link Paul K. 
Published: July 2011

Abstract
Detailed mapping along the east face of Oxford Ridge in the southern Bannock Range, southeast Idaho determines the stratigraphic placement and lateral extent of strata in the Scout Mountain Member of the Neoproterozoic Pocatello Formation. The lower “transitional unit” overlies the Bannock Volcanic Member and consists of 70 m of massive diamictite with argillitic and vesicular basaltic clasts up to cobble size intercalated with thin metabasalt and hyaloclastite units. Overlying the transitional unit is a 150–190-m-thick, massive, brown-green to purple sandy diamictite with dominantly quartzose cobble clasts. Interbedded with this middle unit is a 60-m-thick epiclastic volcanic interval informally named the Oxford Mountain tuffite. An upper sandstone unit up to 100 m thick lies above the diamictite at the head of Fivemile Creek in the southern portion of the map area.
The volcanic interval contains plagioclase-phyric volcanic lithic sandstone, porphyritic volcanic lithic fragments and rounded cobbles in tuffaceous diamictite and a reworked stratified lapilli-tuff. It is interstratified with quartzose and volcanogenic diamictite and can be traced along 5.5 km of strike. On Oxford Mountain, laser ablation–inductively coupled plasma mass spectrometry U-Pb zircon ages presented here and additional sensitive high-resolution ion microprobe ages constrain the underlying Bannock Volcanic Member to be 717–686 Ma and require that the overlying Scout Mountain Member is younger than 685 Ma.
New descriptions of the cap dolostone and associated strata, Neoproterozoic Pocatello Formation, southeastern Idaho, USA
Authors: Dehler Carol M. , Anderson Kathleen , Nagy Robin 
Published: July 2011

Abstract
An ~90-m-thick interval of mixed siliciclastic-carbonate strata, including a cap dolostone unit, overlies diamictite of the upper Scout Mountain Member of the Pocatello Formation in the Fort Hall Mine area south of Portneuf Narrows, southeastern Idaho, and is ≤ ca. 665 Ma. Six facies comprise this interval: silty sandstone (reworked diamictite matrix), laminated dolomite, dolomite and sandstone, sandstone, dolomite-chip breccia, and argillite and limestone. Sedimentary structures and bedding geometries of facies indicate paleoenvironments ranging from below storm wave base to upper shoreface. The edgewise, mounded, and parallel-bedded dolomite-chip breccia indicates slope failure and reworking of the lower shoreface during large storms.
Facies relationships allow generalized division of these strata into three units. The lowermost unit, Unit A, comprises intimately interbedded laminated dolomite (“cap dolostone”), dolomite-chip breccia, and sandstone facies and is 17 m thick. Unit A apparently grades upward into Unit B, a 45-m-thick interval of the sandstone facies. Unit C, 28 m thick, rests sharply on Unit B, and comprises a basal laminated dolomite facies and the limestone and argillite facies. Units A and B may indicate a regressive wave-dominated coast that was influenced by large storms (highstand systems tract). Unit C indicates near storm wave base deposition and an overall deepening, as shown by dark argillite beds of the overlying upper member of the Pocatello Formation (transgressive systems tract).
δ13C and δ18O values from dolomite and limestone samples of Units A and C are similar to values from local, regional, and transglobal cap carbonate intervals. δ13C values range from −1.9 to −5.6‰ and δ18O values range from −10.2 to −17.4‰, with no systematic correlation between C- and O-isotope values. δ13C values are consistent with previously reported values from the Pocatello Formation and are similar to values from the alleged Marinoan Noonday Formation in Death Valley, California, and the Marinoan Maieberg Formation in Namibia.
Collective data from the cap dolostone and associated strata of the Pocatello Formation suggest protracted mixed siliciclastic-carbonate deposition on a stormdominated shelf at ca. 665 Ma.
Secondary hypertension: a condition not to be missed
Authors: Sukor Norlela 
Published: July 2011

ABSTRACT
Hypertension is a chronic disorder which often entails debilitating cardiovascular and renal complications. Hypertension mostly arises as a complex quantitative trait that is affected by varying combinations of genetic and environmental factors. Secondary hypertension has been encountered with increasing frequency. The common causes of secondary hypertension include renal parenchymal disease, renal artery stenosis, primary aldosteronism, phaeochromocytoma, and Cushing’s syndrome. The detection of a secondary cause is of the utmost importance because it provides an opportunity to convert an incurable disease into a potentially curable one. Early identification and treatment will provide a better opportunity for cure, prevent target organ damage, reduce socioeconomic burden and health expenditure associated with drug costs, and improve patients' quality of life. Hence, it is a condition not to be missed.
Synthetic Triterpenoid Cyano Enone of Methyl Boswellate Activates Intrinsic, Extrinsic, and Endoplasmic Reticulum Stress Cell Death Pathways in Tumor Cell Lines
Authors: Ravanan Palaniyandi , Sano Renata , Talwar Priti , Ogasawara Satoshi , Matsuzawa Shu-ichi , Cuddy Michael , Singh Sanjay K. , Rao G.S.R. Subba , Kondaiah Paturu , Reed John C. 
Published: July 2011

AbstractWe explored the effect of a novel synthetic triterpenoid compound cyano enone of methyl boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD50) values in 10 of 10 tumor cell lines tested. CEMB-induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using short interfering RNAs (siRNA), we show evidence that knockdown of caspase 8, DR4, Apaf-1, and Bid impairs CEMB-induced cell death. Similar to other proapoptotic synthetic triterpenoid compounds, CEMB-induced apoptosis involved endoplasmic reticulum stress, as shown by partial rescue of tumor cells by siRNA-mediated knockdown of expression of genes involved in the unfolded protein response such as IRE1α, PERK, and ATF6. Altogether, our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy. Mol Cancer Ther; 10(9); 1635–43. ©2011 AACR.
One-Year Outcomes of Cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry
Authors: Thomas Martyn , Schymik Gerhard , Walther Thomas , Himbert Dominique , Lefèvre Thierry , Treede Hendrik , Eggebrecht Holger , Rubino Paolo , Colombo Antonio , Lange Rüdiger , Schwarz; Rebecca R. , Wendler Olaf 
Published: July 2011

Background—
Transcatheter aortic valve implantation was developed to provide a therapeutic option for patients considered to be ineligible for, and to mitigate mortality and morbidity associated with, high-risk surgical aortic valve replacement.

Methods and Results—

The Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry was designed to assess initial post commercial clinical transcatheter aortic valve implantation results of the Edwards SAPIEN valve in consecutive patients in Europe. Cohort 1 consists of 1038 patients enrolled at 32 centers. One-year outcomes are presented. Patients with the transapical approach (n=575) suffered more comorbidities than transfemoral patients (n=463) with a significantly higher logistic EuroSCORE (29% versus 25.8%;
P
=0.007). These groups are different; therefore, outcomes cannot be directly compared. Total Kaplan Meier 1-year survival was 76.1% overall, 72.1% for transapical and 81.1% for transfemoral patients, and 73.5% of surviving patients were in New York Heart Association (NYHA) class I or II at 1 year. Combined transapical and transfemoral causes of death were cardiac in 25.1%, noncardiac in 49.2%, and unknown in 25.7%. Pulmonary complications (23.9%), renal failure (12.5%), cancer (11.4%), and stroke (10.2%) were the most frequent noncardiac causes of death. Multivariable analysis identified logistic EuroSCORE, renal disease, liver disease, and smoking as variables with the highest hazard ratios for 1-year mortality whereas carotid artery stenosis, hyperlipidemia, and hypertension were associated with lower mortality.

Conclusion—
The SOURCE Registry is the largest consecutively enrolled registry for transcatheter aortic valve implantation procedures. It demonstrates that with new transcatheter aortic techniques excellent 1-year survival in high-risk and inoperable patients is achievable and provides a benchmark against which future transcatheter aortic valve implantation cohorts and devices can be measured.
H11 Kinase/Heat Shock Protein 22 Deletion Impairs Both Nuclear and Mitochondrial Functions of STAT3 and Accelerates the Transition Into Heart Failure on Cardiac Overload
Authors: Qiu Hongyu , Lizano Paulo , Laure Lydie , Sui Xiangzhen , Rashed Eman , Park Ji Yeon , Hong Chull , Gao Shumin , Holle Eric , Morin Didier , Dhar Sunil K. , Wagner Thomas , Berdeaux Alain , Tian Bin , Vatner Stephen F. , Depre Christophe 
Published: July 2011

Background—
Cardiac overload, a major cause of heart failure, induces the expression of the heat shock protein H11 kinase/Hsp22 (Hsp22).

Methods and Results—
To determine the specific function of Hsp22 in that context, a knockout mouse model of Hsp22 deletion was generated. Although comparable to wild-type mice in basal conditions, knockout mice exposed to pressure overload developed less hypertrophy and showed ventricular dilation, impaired contractile function, increased myocyte length and accumulation of interstitial collagen, faster transition into heart failure, and increased mortality. Microarrays revealed that hearts from knockout mice failed to transactivate genes regulated by the transcription factor STAT3. Accordingly, nuclear STAT3 tyrosine phosphorylation was decreased in knockout mice. Silencing and overexpression experiments in isolated neonatal rat cardiomyocytes showed that Hsp22 activates STAT3 via production of interleukin-6 by the transcription factor nuclear factor-κB. In addition to its transcriptional function, STAT3 translocates to the mitochondria where it increases oxidative phosphorylation. Both mitochondrial STAT3 translocation and respiration were also significantly decreased in knockout mice.

Conclusions—
This study found that Hsp22 represents a previously undescribed activator of both nuclear and mitochondrial functions of STAT3, and its deletion in the context of pressure overload in vivo accelerates the transition into heart failure and increases mortality.