bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship Between Fundamental Movement Skills and Physical Self-Perception Among Adolescent Girls
Authors: Rogers Vaimanino , Barnett Lisa M. , Lander Natalie 
Published: October 2018

This study aimed to explore the relationship between fundamental movement skills (FMS) and multiple levels of physical self-perception among early adolescent girls. The Victorian FMS Teachers’ Manual was used to measure actual FMS. Perceptions were measured using the Physical Self-Perception Profile and the Perceived Movement Skill Competence Scale. Pearson’s correlations assessed the association between FMS and each level of physical self-perception. General linear models, adjusting for potential confounders, were conducted to explore the relationship between FMS and multiple levels of physical self-perception. A total of 173 Australian girls (M = 12.48 years,SD = .34) had complete data. Results found positive moderate and significant associations between actual FMS and physical self-perception, perceived sports competence, and, to a lesser degree, perceived FMS. Actual and perceived object control skill were also moderately associated, but there was no association between actual and perceived locomotor skill. After adjusting for potential confounders, FMS remained a significant predictor of each level of perception in each model, except for locomotor skill. These findings are important for future intervention development to improve both actual and perceived FMS, particularly in object control skill, which has been identified as a predictor of subsequent physical activity.
Efficacy and Safety of a 10-Day Course of 400 or 600 Milligrams of Grepafloxacin Once Daily for Treatment of Acute Bacterial Exacerbations of Chronic Bronchitis: Comparison with a 10-Day Course of 500 Milligrams of Ciprofloxacin Twice Daily
Authors: Chodosh S. , Lakshminarayan S. , Swarz H. , Breisch S. 
Published: October 2018

ABSTRACT

A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis. At the end of treatment, clinical success (cure or improvement) was achieved for 93% (140 of 151), 88% (137 of 156), and 91% (145 of 160) of patients in the groups receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively (clinically evaluable population). At follow-up (14 to 28 days posttreatment), the clinical success rates were 87% (124 of 143), 81% (122 of 151), and 80% (123 of 154) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin, respectively. A total of 379 pathogens were isolated from 290 patients, with the most common isolates being
Moraxella catarrhalis
(21%),
Staphylococcus aureus
(20%),
Haemophilus influenzae
(18%), and
Streptococcus pneumoniae
(7%). For the evaluable population, successful bacteriologic response was obtained at the end of treatment for 96% (92 of 96), 98% (87 of 89), and 92% (82 of 90) of patients receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively, and was maintained in 86% (82 of 95), 88% (78 of 89), and 82% (69 of 84) of patients, respectively, at follow-up. All pretreatment
S. pneumoniae
isolates were susceptible to grepafloxacin, but two strains were resistant to ciprofloxacin. All treatments were well tolerated, with the most frequently reported drug-related adverse events being nausea, taste perversion, and headache. All drug-related adverse events in the grepafloxacin groups were mild or moderate in severity. This study demonstrates that 10-day courses of grepafloxacin given at 400 or 600 mg once daily were as effective, clinically and bacteriologically, as ciprofloxacin given at 500 mg twice daily for the treatment of acute bacterial exacerbations of chronic bronchitis.
Antibacterial Efficacy against an In Vivo
Salmonella typhimurium
Infection Model and Pharmacokinetics of a Liposomal Ciprofloxacin Formulation
Authors: Webb Murray S. , Boman Nancy L. , Wiseman David J. , Saxon Dawn , Sutton Kym , Wong Kim F. , Logan Patricia , Hope Michael J. 
Published: October 2018

ABSTRACT

The fluoroquinolone antibiotic ciprofloxacin has been encapsulated into large unilamellar vesicles (LUV) at efficiencies approaching 100%. Drug accumulation proceeded in response to a transmembrane gradient of methylammonium sulfate and occurred concomitantly with the efflux of methylamine. A mechanism for the encapsulation process is described. LUV composed of dipalmitoylphosphatidylcholine-cholesterol (DPPC/chol), distearoylphosphatidylcholine-cholesterol (DSPC/chol), or sphingomyelin-cholesterol (SM/chol) increased the circulation lifetime of ciprofloxacin after intravenous (i.v.) administration by >15-fold. The retention of ciprofloxacin in liposomes in the circulation decreased in the sequence SM/chol > DSPC/chol > DPPC/chol. Increased circulation lifetimes were associated with enhanced delivery of the drug to the livers, spleens, kidneys, and lungs of mice. Encapsulation of ciprofloxacin also conferred significant increases in the longevity of the drug in the plasma after intraperitoneal administration and in the lungs after intratracheal administration in comparison to free ciprofloxacin. The efficacy of a single i.v. administration of an SM/chol formulation of ciprofloxacin was measured in a
Salmonella typhimurium
infection model. At 20 mg of ciprofloxacin per kg of body weight, the encapsulated formulation resulted in 10
3
- to 10
4
-fold fewer viable bacteria in the livers and spleens of infected mice than was observed for animals treated with free ciprofloxacin. These results show the utility of liposomal encapsulation of ciprofloxacin in improving the pharmacokinetics, biodistribution, and antibacterial efficacy of the antibiotic. In addition, these formulations are well suited for i.v., intraperitoneal, and intratracheal or aerosol administration.
Sequencing of Gyrase and Topoisomerase IV Quinolone-Resistance-Determining Regions of
Chlamydia trachomatis
and Characterization of Quinolone-Resistant Mutants Obtained In Vitro
Authors: Dessus-Babus Sophie , Bébéar Cécile M. , Charron Alain , Bébéar Christiane , de Barbeyrac Bertille 
Published: October 2018

ABSTRACT

The L2 reference strain of
Chlamydia trachomatis
was exposed to subinhibitory concentrations of ofloxacin (0.5 μg/ml) and sparfloxacin (0.015 μg/ml) to select fluoroquinolone-resistant mutants. In this study, two resistant strains were isolated after four rounds of selection. The
C. trachomatis
mutants presented with high-level resistance to various fluoroquinolones, particularly to sparfloxacin, for which a 1,000-fold increase in the MICs for the mutant strains compared to the MIC for the susceptible strain was found. The MICs of unrelated antibiotics (doxycycline and erythromycin) for the mutant strains were identical to those for the reference strain. The gyrase (
gyrA
,
gyrB
) and topoisomerase IV (
parC
,
parE
) genes of the susceptible and resistant strains of
C. trachomatis
were partially sequenced. A point mutation was found in the
gyrA
quinolone-resistance-determining region (QRDR) of both resistant strains, leading to a Ser83→Ile substitution (
Escherichia coli
numbering) in the corresponding protein. The
gyrB
,
parC
, and
parE
QRDRs of the resistant strains were identical to those of the reference strain. These results suggest that in
C. trachomatis
, DNA gyrase is the primary target of ofloxacin and sparfloxacin.
Structure-In Vitro Activity Relationships of Pentamidine Analogues and Dication-Substituted Bis-Benzimidazoles as New Antifungal Agents
Authors: Del Poeta Maurizio , Schell Wiley A. , Dykstra Christine C. , Jones Susan , Tidwell Richard R. , Czarny Agnieszka , Bajic Miroslav , Bajic Marina , Kumar Arvind , Boykin David , Perfect John R. 
Published: October 2018

ABSTRACT

Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities against
Candida albicans
and
Cryptococcus neoformans
. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC
80
s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against
C. albicans
had an MIC
80
of ≤0.09 μg/ml, and the most potent compound against
C. neoformans
had an MIC
80
of 0.19 μg/ml. Selected compounds were also found to be active against
Aspergillus fumigatus
,
Fusarium solani
,
Candida
species other than
C. albicans
, and fluconazole-resistant strains of
C. albicans
and
C. neoformans
. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential.
Rifampin Concentrations in Various Compartments of the Human Brain: A Novel Method for Determining Drug Levels in the Cerebral Extracellular Space
Authors: Mindermann Thomas , Zimmerli Werner , Gratzl Otmar 
Published: October 2018

ABSTRACT

Antimicrobial therapy for brain infections is notoriously difficult because of the limited extent of knowledge about drug penetration into the brain. Therefore, we determined the penetration of rifampin into various compartments of the human brain, including the cerebral extracellular space (CES). Patients undergoing craniotomy for resection of primary brain tumors were given a standard dose of 600 mg of rifampin intravenously before the operation. A microdialysis probe (10 by 0.5 mm) was inserted into the cortex distantly from the resection and was perfused with two different rifampin solutions. Rifampin concentrations in the CES were calculated by the no-net-flux method. Intraoperatively, samples were taken from brain tumor tissue, perifocal tissue, and normal brain tissue in the case of pole resections. Rifampin concentrations in the various samples were determined by using a bioassay with
Sarcinea lutea
. In the various compartments, rifampin concentrations were highest within tumors (1.37 ± 1.34 μg/ml;
n
= 8), followed by the perifocal region (0.62 ± 0.67 μg/ml;
n
= 8), the CES (0.32 ± 0.11 μg/ml;
n
= 6), and normal brain tissue (0.29 ± 0.15 μg/ml;
n
= 7). Rifampin concentrations in brain tumors do not adequately reflect concentrations in normal brain tissue or in the CES. Rifampin concentrations in the CES, as determined by microdialysis, are the most reproducible, and the least scattered, of the values for all compartments evaluated. Rifampin concentrations in all compartments exceed the MIC for staphylococci and streptococci. However, CES concentrations may be below the MICs for some mycobacterial strains.
Mechanism of Fluconazole Resistance in
Candida krusei
Authors: Orozco Alison S. , Higginbotham Lindsey M. , Hitchcock Christopher A. , Parkinson Tanya , Falconer Derek , Ibrahim Ashraf S. , Ghannoum Mahmoud A. , Filler Scott G. 
Published: October 2018

ABSTRACT

The mechanisms of fluconazole resistance in three clinical isolates of
Candida krusei
were investigated. Analysis of sterols of organisms grown in the absence and presence of fluconazole demonstrated that the predominant sterol of
C. krusei
is ergosterol and that fluconazole inhibits 14α-demethylase in this organism. The 14α-demethylase activity in cell extracts of
C. krusei
was 16- to 46-fold more resistant to inhibition by fluconazole than was 14α-demethylase activity in cell extracts of two fluconazole-susceptible strains of
Candida albicans
. Comparing the carbon monoxide difference spectra of microsomes from
C. krusei
with those of microsomes from
C. albicans
indicated that the total cytochrome P-450 content of
C. krusei
is similar to that of
C. albicans
. The Soret absorption maximum in these spectra was located at 448 nm for
C. krusei
and at 450 nm for
C. albicans
. Finally, the fluconazole accumulation of two of the
C. krusei
isolates was similar to if not greater than that of
C. albicans
. Thus, there are significant qualitative differences between the 14α-demethylase of
C. albicans
and
C. krusei
. In addition, fluconazole resistance in these strains of
C. krusei
appears to be mediated predominantly by a reduced susceptibility of 14α-demethylase to inhibition by this drug.
Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase
Authors: Sudbeck Elise A. , Mao Chen , Vig Rakesh , Venkatachalam T. K. , Tuel-Ahlgren Lisa , Uckun Fatih M. 
Published: October 2018

ABSTRACT

Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1
H
)-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, <1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 μM.
Pharmacodynamic Evaluation of Factors Associated with the Development of Bacterial Resistance in Acutely Ill Patients during Therapy
Authors: Thomas Jennifer K. , Forrest Alan , Bhavnani Sujata M. , Hyatt Judith M. , Cheng Angela , Ballow Charles H. , Schentag Jerome J. 
Published: October 2018

ABSTRACTThe selection of bacterial resistance was examined in relationship to antibiotic pharmacokinetics (PK) and organism MICs in the patients from four nosocomial lower respiratory tract infection clinical trials. The evaluable database included 107 acutely ill patients, 128 pathogens, and five antimicrobial regimens. Antimicrobial pharmacokinetics were characterized by using serum concentrations, and culture and sensitivity tests were performed daily on tracheal aspirates to examine resistance. Pharmacodynamic (PD) models were developed to identify factors associated with the probability of developing bacterial resistance. Overall, in 32 of 128 (25%) initially susceptible cases resistance developed during therapy. An initial univariate screen and a classification and regression tree analysis identified the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (AUC0–24/MIC) as a significant predictor of the development of resistance (P< 0.001). The final PK/PD model, a variant of the Hill equation, demonstrated that the probability of developing resistance during therapy increased significantly when antimicrobial exposure was at an AUC0–24/MIC ratio of less than 100. This relationship was observed across all treatments and within all organism groupings, with the exception of β-lactamase-producing gram-negative organisms (consistent with type I β-lactamase producers) treated with β-lactam monotherapy. Combination therapy resulted in much lower rates of resistance than monotherapy, probably because all of the combination regimens examined had an AUC0–24/MIC ratio in excess of 100. In summary, the selection of antimicrobial resistance appears to be strongly associated with suboptimal antimicrobial exposure, defined as an AUC0–24/MIC ratio of less than 100.
Comparative In Vitro Activities and Postantibiotic Effects of the Oxazolidinone Compounds Eperezolid (PNU-100592) and Linezolid (PNU-100766) versus Vancomycin against
Staphylococcus aureus
, Coagulase-Negative Staphylococci,
Enterococcus faecalis
, and
Enterococcus faecium
Authors: Rybak Michael J. , Cappelletty Diane M. , Moldovan Tabitha , Aeschlimann Jeffrey R. , Kaatz Glenn W. 
Published: October 2018

ABSTRACT

The activities of the oxazolidinone antibacterial agents eperezolid (PNU-100592) and linezolid (PNU-100766) were compared with that of vancomycin against clinical isolates of methicillin-susceptible and -resistant
Staphylococcus aureus
(
n
= 200), coagulase-negative staphylococci (
n
= 100), and vancomycin-susceptible and -resistant
Enterococcus faecalis
and
Enterococcus faecium
(
n
= 50). Eperezolid and linezolid demonstrated good in vitro inhibitory activity, regardless of methicillin susceptibility for staphylococci (MIC at which 90% of the isolates are inhibited [MIC
90
] range, 1 to 4 μg/ml) or vancomycin susceptibility for enterococci (MIC
90
range, 1 to 4 μg/ml). In time-kill studies, eperezolid and linezolid were bacteriostatic in action. A postantibiotic effect of 0.8 ± 0.5 h was demonstrated for both eperezolid and linezolid against
S. aureus
,
S. epidermidis
,
E. faecalis
, and
E. faecium.
Role of ABC Transporters in Aureobasidin A Resistance
Authors: Ogawa Atsuko , Hashida-Okado Takashi , Endo Masahiro , Yoshioka Hirofumi , Tsuruo Takashi , Takesako Kazutoh , Kato Ikunoshin 
Published: October 2018

ABSTRACT

Aureobasidin A (AbA) has strong antifungal effects arising from an unusual mechanism. We show that AbA interacts with ATP-binding cassette (ABC) transporters in yeast and mammalian cells. We isolated a gene of
Saccharomyces cerevisiae
that conferred resistance to AbA when the gene was present in multiple copies. The gene was identical to
YOR1/YRS1
, which confers resistance to oligomycin, reveromycin, and organic anions, none of which have structures similar to that of AbA. We also isolated an
aur3
R
recessive mutant of
S. cerevisiae
with increased resistance to AbA. Northern hybridization showed that the
aur3
R
mutant expressed not only
YOR1
but also the ABC transporter-encoding gene
PDR5
at high levels. Genetic studies showed that the
aur3
R
mutant had a mutation in the
PDR1
gene, which encodes a transcriptional regulator of
PDR5
and
YOR1
. Analysis of a
yor1
disruptant of the
aur3/pdr1
mutant showed that both the functional
YOR1
gene and the mutation in
PDR1
were necessary for AbA resistance. These results suggest that
YOR1
is more important than
PDR5
for AbA resistance. We found in
Candida albicans
a novel gene whose sequence was similar to the sequence of
YOR1
in
S. cerevisiae
. The amino acid sequence of the
C. albicans YOR1
homolog showed no significant similarity to the sequences of
CDR1
and
CDR2
, which are ABC transporters of
C. albicans
. Furthermore, AbA inhibited the efflux of the anticancer agent vincristine through P glycoproteins in cancer cells with multidrug resistance.
In Vitro and In Vivo Antifungal Activity of Amphotericin B Lipid Complex: Are Phospholipases Important?
Authors: Swenson Christine E. , Perkins Walter R. , Roberts Patricia , Ahmad Imran , Stevens Rachel , Stevens David A. , Janoff Andrew S. 
Published: October 2018

ABSTRACT

Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin B complexed with the lipids
l
-α-dimyristoylphosphatidylcholine (DMPC) and
l
-α-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Active amphotericin B can be released from ABLC by exogenously added (snake venom, bacteria, or
Candida
-derived) phospholipases or by phospholipases derived from activated mammalian vascular tissue (rat arteries). Such extracellular phospholipases are capable of hydrolyzing the major lipid in ABLC. Mutants of
C. albicans
that were resistant to ABLC but not AmB-d in vitro were deficient in extracellular phospholipase activity, as measured on egg yolk agar or as measured by their ability to hydrolyze DMPC in ABLC. ABLC was nevertheless effective in the treatment of experimental murine infections produced by these mutants. Isolates of
Aspergillus
species, apparently resistant to ABLC in vitro (but susceptible to AmB-d), were also susceptible to ABLC in vivo. We suggest that routine in vitro susceptibility tests with ABLC itself as the test material may not accurately predict the in vivo activity of ABLC and that the enhanced therapeutic index of ABLC relative to that of AmB-d in vivo may be due, in part, to the selective release of active amphotericin B from the complex at sites of fungal infection through the action of fungal or host cell-derived phospholipases.
Characterization of the Antimonial Antileishmanial Agent Meglumine Antimonate (Glucantime)
Authors: Roberts William L. , McMurray Walter J. , Rainey Petrie M. 
Published: October 2018

ABSTRACT

Meglumine antimonate (Glucantime), a drug of choice for the treatment of leishmaniasis, is produced by the reaction of pentavalent antimony with
N
-methyl-
d
-glucamine, a carbohydrate derivative. We investigated the structure and composition of meglumine antimonate, which remain poorly understood, despite 50 years of use. Measurement of the antimony content of meglumine antimonate powder indicated a 1:1.37 molar ratio of antimony to
N
-methyl-
d
-glucamine. Osmolality measurements performed with meglumine antimonate solutions demonstrated an average of 1.43 antimony atoms per molecule of meglumine antimonate. The osmolality of a 1:10 dilution of stock meglumine antimonate increased by 45% over 8 days, suggesting hydrolysis to less complex species. A comparison of the proton nuclear magnetic resonance spectra of
N
-methyl-
d
-glucamine and meglumine antimonate revealed an increase in complexity in the latter but with all of the resonances of the former still being evident, consistent with the presence of coordination complexes between antimony and each of the
N
-methyl-
d
-glucamine hydroxyls. Fast atom bombardment and electrospray ionization mass spectrometry coupled with several derivatization procedures provided evidence that up to four
N
-methyl-
d
-glucamine hydroxyls are coordinated with each antimony. A series of oligomers were observed. The major moiety has a molecular mass of 507 atomic mass units and consists of NMG-Sb-NMG, where Sb represents antimony and NMG represents
N
-methyl-
d
-glucamine. Additional species containing up to four antimony atoms and five
N
-methyl-
d
-glucamine moieties and corresponding to the general form (NMG-Sb)

n

-NMG are also present. These results suggest that this agent is a complex mixture that exists in equilibrium in aqueous solution.
A New High-Level Gentamicin Resistance Gene,
aph(2")-Id
, in
Enterococcus
spp
Authors: Tsai Shane F. , Zervos Marcus J. , Clewell Don B. , Donabedian Susan M. , Sahm Daniel F. , Chow Joseph W. 
Published: October 2018

ABSTRACT

Enterococcus casseliflavus
UC73 is a clinical blood isolate with high-level resistance to gentamicin. DNA preparations from UC73 failed to hybridize with intragenic probes for
aac(6′)-Ie-aph(2")-Ia
and
aph(2")-Ic
. A 4-kb fragment from UC73 was cloned and found to confer resistance to gentamicin in
Escherichia coli
DH5α transformants. Nucleotide sequence analysis revealed the presence of a 906-bp open reading frame whose deduced amino acid sequence had a region with homology to the aminoglycoside-modifying enzyme APH(2")-Ic and to the C-terminal domain of the bifunctional enzyme AAC(6′)-APH(2"). The gene is designated
aph(2")-Id
, and its observed phosphotransferase activity is designated APH(2")-Id. A PCR-generated intragenic probe hybridized to the genomic DNA from 17 of 118 enterococcal clinical isolates (108 with high-level gentamicin resistance) from five hospitals. All 17 were vancomycin-resistant
Enterococcus faecium
isolates, and pulsed-field typing revealed three distinct clones. The combination of ampicillin plus either amikacin or neomycin exhibited synergistic killing against
E. casseliflavus
UC73. Screening and interpretation of high-level aminoglycoside resistance in enterococci may need to be modified to include detection of APH(2")-Id.