bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fe‐Mg interdiffusion profiles in rimmed forsterite grains in the Allende matrix: Time–temperature constraints for the parent body metamorphism
Authors: Cuvillier Priscille , Leroux Hugues , Jacob Damien , Hirel Pierre 
Published: August 2015

AbstractThe Allende matrix is dominated by micron‐sized lath‐shaped fayalitic olivine grains with a narrow compositional range (Fa40–50). Fayalitic olivines also occur as rims around forsterite grains in chondrules and isolated forsterite fragments in the matrix or as veins cross‐cutting the grains. Allende is a type 3 CV carbonaceous chondrite having experienced a moderate thermal metamorphism. There is therefore a strong chemical disequilibrium between the large forsterite grains and the fayalite‐rich fine‐grained matrix. Chemical gradients at interfaces are poorly developed and thus not accessible using conventional techniques. Here, we used analytical transmission electron microscopy to study the microstructure of the fayalite‐rich matrix grains and interfaces with forsterite fragments. We confirm that fayalitic grains in the matrix and fayalitic rims around forsterite fragments have the same properties, suggesting a common origin after the accretion of the parent body of Allende. Composition profiles at the rim/forsterite interfaces exhibit a plateau in the rim (typically Fa45), a compositional jump of 10 Fa% at the interface, and a concentration gradient in the forsterite grain. Whatever the studied forsterite grain or whatever the nature of the interface, the Fe‐Mg profiles in forsterite grains have the same length of about 1.5 μm. This strongly suggests that the composition profiles were formed by solid‐state diffusion during the thermal metamorphism episode. Time–temperature couples associated with the diffusion process during thermal metamorphism are deduced from profile modeling. Considering the uncertainties on the diffusion coefficient value, we found that the peak temperature in Allende is ranging from 425 to 505 °C.
Analytical Model for Viscous Wall Dampers
Authors: Hejazi F. , Shoaei M. Dalili , Tousi A. , Jaafar M. S. 
Published: August 2015

AbstractBy now, many civil engineering researchers have extensively studied the application of earthquake energy dissipation systems in seismic‐resistant buildings. Earthquake energy dissipation systems play an important role in enhancing the sustainability of structures against seismic excitation. Frame buildings are strengthened by installing damper devices as supplemental structural members. This article presents the finite‐element‐based development of an analytical model for a viscous wall damper (VWD) device, an alternative to other earthquake energy dissipation systems, which can diminish the effect of earthquakes on structures and improve the seismic performance of multistory buildings subjected to ground motion. The constitutive law of VWDs has been formulated and integrated to develop a finite element model of VWD compatible with the reinforced concrete (RC) structure analytical model. Then, the finite element algorithm has been developed for inelastic analysis of RC buildings equipped with VWD devices capable of detecting damage to both structural members and damper connections under dynamic loading. Based on the developed system, the special finite element program was codified and verified by applying it to a real model of a RC building with supplementary VWD devices. Influence of VWDs on seismic performance of the RC building during earthquake excitation was evaluated. The proposed analytical model for VWD is verified by using experimental test data and analysis result proved that this energy dissipation system succeeds by substantially diminishing and dissipating a structure's induced seismic responses. Also the parametric study indicated that the damping coefficient is very effective on performance of VWD.
WRKY40 and WRKY6 act downstream of the green leaf volatile E‐2‐hexenal in Arabidopsis
Authors: Mirabella Rossana , Rauwerda Han , Allmann Silke , Scala Alessandra , Spyropoulou Eleni A. , de Vries Michel , Boersma Maaike R. , Breit Timo M. , Haring Michel A. , Schuurink Robert C. 
Published: August 2015

SummaryPlants are known to be responsive to volatiles, but knowledge about the molecular players involved in transducing their perception remains scarce. We study the response of Arabidopsis thaliana to E‐2‐hexenal, one of the green leaf volatiles (GLV) that is produced upon wounding, herbivory or infection with pathogens. We have taken a transcriptomics approach to identify genes that are induced by E‐2‐hexenal, but not by defence hormones or other GLVs. Furthermore, by studying the promoters of early E‐2‐hexenal‐induced genes we determined that the only statistically enriched cis‐element was the W‐box motif. Since members of the plant‐specific family of WRKY transcription factors act in trans on this cis‐element, we focused on WRKY6, 40 and 53 that were most strongly induced by E‐2‐hexenal. Root elongation of Arabidopsis seedlings of the wrky40 wrky6 double mutant was much less inhibited than in wt plants, similar to the E‐2‐hexenal‐responsive mutant her1, which is perturbed in γ‐amino butyric acid (GABA) metabolism. The induction of several of the E‐2‐hexenal‐specific genes was much higher in the wrky40, wrky6 or wrky40 wrky6 mutants, including GAD4, a glutamate decarboxylase that catalyzes the formation of GABA from glutamate. In conclusion, WRKY6 and 40 seem to act as important players transducing E‐2‐hexenal perception.
The Effectiveness of Clinically Indicated Replacement of Peripheral Intravenous Catheters: An Evidence Review With Implications for Clinical Practice
Authors: Morrison Kimberly , Holt Karyn E. 
Published: August 2015

ABSTRACTBackgroundCurrent clinical guidelines from the Centers for Disease Control and Prevention (CDC; 2011) state that peripheral intravenous catheters are to be replaced every 72–96 hr to prevent infection and phlebitis in the adult patient. It is unclear whether this practice reduces the incidence of phlebitis or other infections.AimThe aim of this study was to examine levels I and II evidence to determine if replacing peripheral intravenous catheters only when clinically indicated compared to every 72–96 hr increases the adult patient's risk for infection or phlebitis.MethodsThe following patient or population, intervention, comparison, outcome question was used to search the literature databases PubMed, ClinicalKey, ProQuest, Ovid SP, and CINAHL: In the adult patient requiring a peripheral vascular catheter (P), does replacing the catheter only when clinically indicated (I) compared to replacing the catheter every 72–96 hr (C) increase the occurrence of phlebitis and infection (O)? A set of specific search criteria along with critical appraisal tools was used to identify relative studies.ResultsFour level II randomized controlled trials with no less than 155 subjects, and two level I meta‐analyses reviewing a total of 13 research studies indicated that the replacement of peripheral intravenous catheters only when clinically indicated does not increase patient risk of phlebitis or infection when compared to the current practice of routine replacement between 72 and 96 hr in the adult patient population.Linking Evidence to ActionThe current practice of replacing peripheral intravenous catheters every 72–96 hr does not decrease the incidence of phlebitis or infection when compared to replacing catheters when clinically indicated in the adult population. By translating this research into current practice, healthcare costs and nursing care time will decrease, and unnecessary invasive procedures would be eliminated thereby increasing patient safety and satisfaction.
How Robust Are Malaria Parasite Clearance Rates as Indicators of Drug Effectiveness and Resistance?
Authors: Hastings Ian M. , Kay Katherine , Hodel Eva Maria 
Published: August 2015

ABSTRACT
Artemisinin-based combination therapies (ACTs) are currently the first-line drugs for treating uncomplicated falciparum malaria, the most deadly of the human malarias. Malaria parasite clearance rates estimated from patients' blood following ACT treatment have been widely adopted as a measure of drug effectiveness and as surveillance tools for detecting the presence of potential artemisinin resistance. This metric has not been investigated in detail, nor have its properties or potential shortcomings been identified. Herein, the pharmacology of drug treatment, parasite biology, and human immunity are combined to investigate the dynamics of parasite clearance following ACT. This approach parsimoniously recovers the principal clinical features and dynamics of clearance. Human immunity is the primary determinant of clearance rates, unless or until artemisinin killing has fallen to near-ineffective levels. Clearance rates are therefore highly insensitive metrics for surveillance that may lead to overconfidence, as even quite substantial reductions in drug sensitivity may not be detected as lower clearance rates. Equally serious is the use of clearance rates to quantify the impact of ACT regimen changes, as this strategy will plausibly miss even very substantial increases in drug effectiveness. In particular, the malaria community may be missing the opportunity to dramatically increase ACT effectiveness through regimen changes, particularly through a switch to twice-daily regimens and/or increases in artemisinin dosing levels. The malaria community therefore appears overreliant on a single metric of drug effectiveness, the parasite clearance rate, that has significant and serious shortcomings.
Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness
Authors: Kay Katherine , Hodel Eva Maria , Hastings Ian M. 
Published: August 2015

ABSTRACT

There is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 10
12
parasites, while the standard dosing regimens allow approximately 1 in 10
10
parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 10
17
parasites if the dose is extended or split; theoretically, this increase in drug killing appears to be more than sufficient to restore failing ACT efficacy. One of the most widely used dosing regimens, artemether-lumefantrine, already successfully employs a twice-daily dosing regimen, and we argue that twice-daily dosing should be incorporated into all ACT regimen design considerations as a simple and effective way of ensuring the continued long-term effectiveness of ACTs.
Evaluation of Gallium Citrate Formulations against a Multidrug-Resistant Strain of Klebsiella pneumoniae in a Murine Wound Model of Infection
Authors: Thompson Mitchell G. , Truong-Le Vu , Alamneh Yonas A. , Black Chad C. , Anderl Jeff , Honnold Cary L. , Pavlicek Rebecca L. , Abu-Taleb Rania , Wise Matthew C. , Hall Eric R. , Wagar Eric J. , Patzer Eric , Zurawski Daniel V. 
Published: August 2015

ABSTRACT

Skin and soft tissue infections (SSTIs) are a common occurrence in health care facilities with a heightened risk for immunocompromised patients.
Klebsiella pneumoniae
has been increasingly implicated as the bacterial agent responsible for SSTIs, and treatment can be challenging as more strains become multidrug resistant (MDR). Therefore, new treatments are needed to counter this bacterial pathogen. Gallium complexes exhibit antimicrobial activity and are currently being evaluated as potential treatment for bacterial infections. In this study, we tested a topical formulation containing gallium citrate (GaCi) for the treatment of wounds infected with
K. pneumoniae
. First, the MIC against
K. pneumoniae
ranged from 0.125 to 2.0 μg/ml GaCi. After this
in vitro
efficacy was established, two topical formulations with GaCi (0.1% [wt/vol] and 0.3% [wt/vol]) were tested in a murine wound model of MDR
K. pneumoniae
infection. Gross pathology and histopathology revealed
K. pneumoniae
-infected wounds appeared to close faster with GaCi treatment and were accompanied by reduced inflammation compared to those of untreated controls. Similarly, quantitative indications of infection remediation, such as reduced weight loss and wound area, suggested that treatment improved outcomes compared to those of untreated controls. Bacterial burdens were measured 1 and 3 days following inoculation, and a 0.5 to 1.5 log reduction of CFU was observed. Lastly, upon scanning electron microscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings compared to those of untreated controls. These results suggest that with more preclinical testing, a topical application of GaCi may be a promising alternative treatment strategy for
K. pneumoniae
SSTI.
N
-Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans
Authors: Lackner Michaela , Binder Ulrike , Reindl Martin , Gönül Beyhan , Fankhauser Hannes , Mair Christian , Nagl Markus 
Published: August 2015

ABSTRACT

N
-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against
Scedosporium
and
Lomentospora
, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of
Scedosporium apiospermum
,
Scedosporium boydii
, and
Lomentospora prolificans
(formerly
Scedosporium prolificans
) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log
10
reduction in CFU after 4 h and a 4- to >6-log
10
reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of
Galleria mellonella
infected with 1.0 × 10
7
conidia of
S. apiospermum
and
S. boydii
died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different
Scedosporium
and
Lomentospora
species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.
Use of a Combination Biomarker Algorithm To Identify Medical Intensive Care Unit Patients with Suspected Sepsis at Very Low Likelihood of Bacterial Infection
Authors: Han Jennifer H. , Nachamkin Irving , Coffin Susan E. , Gerber Jeffrey S. , Fuchs Barry , Garrigan Charles , Han Xiaoyan , Bilker Warren B. , Wise Jacqueleen , Tolomeo Pam , Lautenbach Ebbing ,   for the Prevention Epicenters Program of the Centers for Disease ControlPrevention
Published: August 2015

ABSTRACT
Sepsis remains a diagnostic challenge in the intensive care unit (ICU), and the use of biomarkers may help in differentiating bacterial sepsis from other causes of systemic inflammatory syndrome (SIRS). The goal of this study was to assess test characteristics of a number of biomarkers for identifying ICU patients with a very low likelihood of bacterial sepsis. A prospective cohort study was conducted in a medical ICU of a university hospital. Immunocompetent patients with presumed bacterial sepsis were consecutively enrolled from January 2012 to May 2013. Concentrations of nine biomarkers (α-2 macroglobulin, C-reactive protein [CRP], ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) were determined at baseline and at 24 h, 48 h, and 72 h after enrollment. Performance characteristics were calculated for various combinations of biomarkers for discrimination of bacterial sepsis from other causes of SIRS. Seventy patients were included during the study period; 31 (44%) had bacterial sepsis, and 39 (56%) had other causes of SIRS. PCT and CRP values were significantly higher at all measured time points in patients with bacterial sepsis. A number of combinations of PCT and CRP, using various cutoff values and measurement time points, demonstrated high negative predictive values (81.1% to 85.7%) and specificities (63.2% to 79.5%) for diagnosing bacterial sepsis. Combinations of PCT and CRP demonstrated a high ability to discriminate bacterial sepsis from other causes of SIRS in medical ICU patients. Future studies should focus on the use of these algorithms to improve antibiotic use in the ICU setting.
Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays
Authors: Vera Omaira , Brelas de Brito Paula , Albrecht Letusa , Martins-Campos Keillen Monick , Pimenta Paulo F. P. , Monteiro Wuelton M. , Lacerda Marcus V. G. , Lopes Stefanie C. P. , Costa Fabio T. M. 
Published: August 2015

ABSTRACT

Significant progress toward the control of malaria has been achieved, especially regarding
Plasmodium falciparum
infections. However, the unique biology of
Plasmodium vivax
hampers current control strategies. The early appearance of
P. vivax
gametocytes in the peripheral blood and the impossibility of culturing this parasite are major drawbacks. Using blood samples from 40
P. vivax
-infected patients, we describe here a methodology to purify viable gametocytes and further infect anophelines. This method opens new avenues to validate transmission-blocking strategies.
Pharmacokinetic Modeling of Lamivudine and Zidovudine Triphosphates Predicts Differential Pharmacokinetics in Seminal Mononuclear Cells and Peripheral Blood Mononuclear Cells
Authors: Dumond Julie B. , Yang Kuo H. , Kendrick Racheal , Reddy Y. Sunila , Kashuba Angela D. M. , Troiani Luigi , Bridges Arlene S. , Fiscus Susan A. , Forrest Alan , Cohen Myron S. 
Published: August 2015

ABSTRACT

The male genital tract is a potential site of viral persistence. Therefore, adequate concentrations of antiretrovirals are required to eliminate HIV replication in the genital tract. Despite higher zidovudine (ZDV) and lamivudine (3TC) concentrations in seminal plasma (SP) than in blood plasma (BP) (SP/BP drug concentration ratios of 2.3 and 6.7, respectively), we have previously reported lower relative intracellular concentrations of their active metabolites, zidovudine triphosphate (ZDV-TP) and lamivudine triphosphate (3TC-TP), in seminal mononuclear cells (SMCs) than in peripheral blood mononuclear cells (PBMCs) (SMC/PBMC drug concentration ratios of 0.36 and 1.0, respectively). Here, we use population pharmacokinetic (PK) modeling-based methods to simultaneously describe parent and intracellular metabolite PK in blood, semen, and PBMCs and SMCs. From this model, the time to steady state in each matrix was estimated, and the results indicate that the PK of 3TC-TP and ZDV-TP in PBMCs are different from the PK of the two in SMCs and different for the two triphosphates. We found that steady-state conditions in PBMCs were achieved within 2 days for ZDV-TP and 3 days for 3TC-TP. However, steady-state conditions in SMCs were achieved within 2 days for ZDV-TP and 2 weeks for 3TC-TP. Despite this, or perhaps because of it, ZDV-TP in SMCs does not achieve the surrogate 50% inhibitory concentration (IC
50
) (as established for PBMCs, assuming SMC IC
50
= PBMC IC
50
) at the standard 300-mg twice-daily dosing. Mechanistic studies are needed to understand these differences and to explore intracellular metabolite behavior in SMCs for other nucleoside analogues used in HIV prevention, treatment, and cure.
Potent
In Vitro
Antiproliferative Synergism of Combinations of Ergosterol Biosynthesis Inhibitors against Leishmania amazonensis
Authors: de Macedo-Silva S. T. , Visbal G. , Urbina J. A. , de Souza W. , Rodrigues J. C. F. 
Published: August 2015

ABSTRACT

Leishmaniases comprise a spectrum of diseases caused by protozoan parasites of the
Leishmania
genus. Treatments available have limited safety and efficacy, high costs, and difficult administration. Thus, there is an urgent need for safer and more-effective therapies. Most trypanosomatids have an essential requirement for ergosterol and other 24-alkyl sterols, which are absent in mammalian cells. In previous studies, we showed that
Leishmania amazonensis
is highly susceptible to aryl-quinuclidines, such as E5700, which inhibit squalene synthase, and to the azoles itraconazole (ITZ) and posaconazole (POSA), which inhibit C-14α-demethylase. Herein, we investigated the antiproliferative, ultrastructural, and biochemical effects of combinations of E5700 with ITZ and POSA against
L. amazonensis
. Potent synergistic antiproliferative effects were observed against promastigotes, with fractional inhibitory concentration (FIC) ratios of 0.0525 and 0.0162 for combinations of E5700 plus ITZ and of E5700 plus POSA, respectively. Against intracellular amastigotes, FIC values were 0.175 and 0.1125 for combinations of E5700 plus ITZ and E5700 plus POSA, respectively. Marked alterations of the ultrastructure of promastigotes treated with the combinations were observed, in particular mitochondrial swelling, which was consistent with a reduction of the mitochondrial transmembrane potential, and an increase in the production of reactive oxygen species. We also observed the presence of vacuoles similar to autophagosomes in close association with mitochondria and an increase in the number of lipid bodies. Both growth arrest and ultrastructural/biochemical alterations were strictly associated with the depletion of the 14-desmethyl endogenous sterol pool. These results suggest the possibility of a novel combination therapy for the treatment of leishmaniasis.
In Vitro
Activities of Eight Antifungal Drugs against a Global Collection of Genotyped Exserohilum Isolates
Authors: Chowdhary Anuradha , Hagen Ferry , Curfs-Breuker Ilse , Madrid Hugo , de Hoog G. Sybren , Meis Jacques F. 
Published: August 2015

ABSTRACT

The
in vitro
susceptibilities of 24 worldwide
Exserohilum
isolates belonging to 10 species from human and environmental sources were determined for eight antifungal drugs. The strains were characterized by internal transcribed spacer (ITS) sequencing and amplified fragment length polymorphism fingerprinting. Posaconazole had the lowest geometric mean MIC (0.16 μg/ml), followed by micafungin (0.21 μg/ml), amphotericin B (0.24 μg/ml), itraconazole (0.33 μg/ml), voriconazole (0.8 μg/ml), caspofungin (1.05 μg/ml), isavuconazole (1.38 μg/ml), and fluconazole (15.6 μg/ml).