bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Impairment of Frontal‐Executive Cognitive Function in African Americans with Cardiovascular Risk Factors
Authors: Pugh Kenneth G. , Kiely Dan K. , Milberg William P. , Lipsitz Lewis A. 
Published: September 2003

Objectives: To determine whether a summary cardiovascular risk score is associated with an increased risk of frontal‐executive cognitive impairment.Design: Cross‐sectional study.Setting: Subjects were recruited from senior centers, senior housing complexes, and communities in the Boston metropolitan area.Participants: Forty‐three predominantly female elderly African Americans.Measurements: Cardiovascular risk factors were assessed during an interview and clinical examination. For each subject, the total number of cardiovascular (CV) risk factors was summed to compute a CV risk score. A battery of neuropsychological tests was administered that examined memory, visuospatial abilities, and frontal‐executive functions. Cognitive test scores were transformed into domain‐specific (memory, visuospatial, frontal‐executive) composite z scores. Cognitive impairment for each composite z score was defined as performance less than the median for the study group. Multivariate logistic regression was used to examine the relationship between the CV risk score and the risk for cognitive impairment in the three cognitive domains of interest.Results: After controlling for age and education, the CV risk score was associated only with frontal‐executive cognitive impairment (odds ratio (OR)=2.44, 95% confidence interval (CI)=1.06–5.65). The CV risk score was not associated with the risk of memory (OR=1.30, 95% CI=0.64–2.67) or visuospatial impairment (OR=1.49, 95% CI=0.66–3.36). Greater CV risk scores were associated with an increased likelihood of having frontal‐executive cognitive impairment.Conclusion: CV risk factors may exert a specific deleterious effect on frontal‐executive cognitive abilities as opposed to memory or visuospatial functions. Associated executive dysfunction may compromise the ability of patients with CV risk factors to comply with recommendations for risk reduction.
Vascular Disease and Cognitive Function: Evidence from the Whitehall II Study
Authors: Singh‐Manoux Archana , Britton Annie R. , Marmot Michael 
Published: September 2003

Objectives: To test the hypothesis of an inverse association between indicators of vascular disease and cognitive function in the general, stroke‐free population.Design: A longitudinal, British civil service–based cohort study. Measures of vascular disease examined were prevalent at baseline or traced over a median of 11 years, between Phases 1 (1985–1988) and 5 (1997–1999) of data collection. Cognitive function was assessed at Phase 5 of data collection.Setting: Twenty London‐based Civil Service departments.Participants: Four thousand one hundred forty‐one men and 1,681 women, aged 46 to 68 when tested for cognitive function.Measurements: A battery of cognitive tests consisting of: memory test, Alice Heim 4, Mill‐Hill, phonemic, and semantic fluency.Results: The occurrence of angina pectoris (P<.001), myocardial infarction (P=.02), all coronary heart disease (P<.001), and intermittent claudication (P=.004) was associated with poor cognitive function. These effects were independent of age and socioeconomic status. The association between indicators of vascular disease and cognitive function applied to the entire range of cognitive function measures examined in the study.Conclusion: The findings support the view that vascular disease is predictive of poor cognitive function in the general population. The fact that presence of vascular disease was associated with diminished cognitive function even in a relatively young cohort has implications for the management of vascular disease.
Training Caregivers to Change the Sleep Hygiene Practices of Patients with Dementia: The NITE‐AD Project
Authors: McCurry Susan M. , Gibbons Laura E. , Logsdon Rebecca G. , Vitiello Michael , Teri Linda 
Published: September 2003

Objectives: To examine the feasibility of training caregivers to implement sleep hygiene recommendations in dementia patients.Design: A randomized, controlled trial.Setting: Community.Participants: Twenty‐two community‐dwelling patients with Alzheimer's disease (AD) and their family caregivers.Interventions: All participants received written materials describing age‐ and dementia‐related changes in sleep and standard principles of good sleep hygiene. Caregivers in active treatment (n=10) also received specific recommendations about setting up and implementing a sleep hygiene program for the dementia patient. Control subjects (n=12) received general dementia education and caregiver support.Measurements: Success implementing sleep hygiene recommendations was measured using daily log reports to calculate the percentage of days that caregivers reported that patients met individualized sleep scheduling, daytime‐napping, and walking goals.Results: Caregivers in active treatment were more successful in setting goals related to sleep scheduling and increasing daytime activity than control caregivers who received written materials only. Among patients who were candidates for sleep hygiene changes, active treatment subjects were also significantly (P<.01) more likely than controls to maintain a consistent bedtime (83% vs 38% of days attempted) and a consistent rising time (96% vs 59%), to nap less during the day (70% vs 28%), and to walk daily (86% vs 7%).Conclusion: This study provides evidence that sleep hygiene interventions are feasible with community‐dwelling AD patients. Caregivers were able to help patients change sleep scheduling, napping, and walking routines, but clinicians who recommend sleep hygiene changes for their dementia patients should be aware that many caregivers need active assistance setting up and implementing a sleep hygiene program. Simply providing caregivers with education is often insufficient.
It's Still Caveat, Inventor
Authors: Udell Gerald G. 
Published: September 2003

Independent inventors are major contributors to industrial innovation and provide an important source of new products to industry. However, they are more often abused than appreciated by the marketplace. In addition, they frequently lack the skills, knowledge and resources either to translate their inventions into innovations or to transfer them effectively to others.In this article, Gerald G. Udell describes the invention development and commercialization services available to independent inventors. He places particular emphasis on the growing problem of ineffectual and perhaps fraudulent invention marketing and promotion in the United States.
Intrinsic Macrolide Resistance in
Mycobacterium smegmatis
Is Conferred by a Novel
erm
Gene,
erm
(38)
Authors: Nash Kevin A. 
Published: September 2003

ABSTRACT

High-level, acquired macrolide resistance in mycobacteria is conferred by mutation within the 23S rRNA gene. However, several mycobacteria are naturally resistant to macrolides, including the
Mycobacterium smegmatis
group and
Mycobacterium tuberculosis
complex. Thus, the aim of this study was to characterize this resistance. Intrinsic macrolide resistance in
M. smegmatis
was inducible and showed cross-resistance to lincosamides but not to streptogramin B (i.e., ML resistance). A similar phenotype was found with
Mycobacterium microti
and macrolide-resistant
Mycobacterium fortuitum
. A search of the DNA sequence data for
M. smegmatis
strain mc
2
155 identified a novel
erm
gene,
erm
(38), and expression analysis showed that
erm
(38) RNA levels increased >10-fold after a 2-h incubation with macrolide. Inducible ML resistance was not expressed by an
erm
(38) knockout mutant, and complementation of this mutant with intact
erm
(38) in
trans
resulted in high-level ML resistance (e.g., clarithromycin MIC of >512 μg/ml). Thus, the results indicate that
erm
(38) confers the intrinsic ML resistance of
M. smegmatis
. Southern blot analysis with an
erm
(38)-specific probe indicated that a similar gene may be present in macrolide-resistant
M. fortuitum
. This finding, with the presence of the
erm
(37) gene (Rv1988) in the
M. tuberculosis
complex, suggests that such genes are widespread in mycobacteria with intrinsic macrolide resistance.
Antibiotic-Dependent Induction of
Pseudomonas putida
DOT-T1E TtgABC Efflux Pump Is Mediated by the Drug Binding Repressor TtgR
Authors: Terán Wilson , Felipe Antonia , Segura Ana , Rojas Antonia , Ramos Juan-Luis , Gallegos María-Trinidad 
Published: September 2003

ABSTRACT

Pseudomonas putida
is well known for its metabolic capabilities, but recently, it has been shown to exhibit resistance to a wide range of antibiotics. In
P. putida
DOT-T1E, the TtgABC efflux pump, which has a broad substrate specificity, extrudes antibiotics such as ampicillin, carbenicillin, tetracycline, nalidixic acid, and chloramphenicol. We have analyzed the expression of the
ttgABC
efflux pump operon and its regulatory gene,
ttgR
, in response to several structurally unrelated antibiotics at the transcriptional level and investigated the role of the TtgR protein in this process.
ttgABC
and
ttgR
are expressed in vivo at a moderate basal level, which increases in the presence of hydrophobic antibiotics like chloramphenicol and tetracycline. In vitro experiments show that, in the absence of inducers, TtgR binds to a palindromic operator site which overlaps both
ttgABC
and
ttgR
promoters and dissociates from it in the presence of chloramphenicol and tetracycline. These results suggest that the TtgR repressor is able to bind to structurally different antibiotics, which allows induction of TtgABC multidrug efflux pump expression in response to these antimicrobial agents. This is the first case in which the expression of a drug transporter of the resistance-nodulation-division family has been shown to be regulated directly by antibiotics.
Antimony Uptake Systems in the Protozoan Parasite
Leishmania
and Accumulation Differences in Antimony-Resistant Parasites
Authors: Brochu Christian , Wang Jingyu , Roy Gaétan , Messier Nadine , Wang Xiao-Yan , Saravia Nancy G. , Ouellette Marc 
Published: September 2003

ABSTRACT

The first line drug against leishmaniasis consists of pentavalent antimony [Sb(V)], but there is general belief that the active form of the metal is the trivalent form [Sb(III)]. In this study, we have quantified the accumulation of Sb(V) and Sb(III) in
Leishmania
by using inductively coupled plasma mass spectrometry. The accumulation was studied in three
Leishmania
species at various life stages, sensitive or resistant to antimony. Both Sb(III) and Sb(V) are accumulated in promastigote and amastigote parasites, but through competition experiments with arsenite, we found that the routes of entry of Sb(V) and Sb(III) are likely to differ in
Leishmania
. The level of accumulation of either Sb(III) or Sb(V), however, was not correlated with the susceptibility of wild-type
Leishmania
cells to antimony. This suggests that other factors may also be implicated in the mode of action of the drugs. In contrast to metal susceptibility, resistance to Sb(III) correlated well with decreased antimony accumulation. This phenotype was energy dependent and highlights the importance of transport systems in drug resistance of this protozoan parasite.
Multilaboratory Comparison of Proficiencies in Susceptibility Testing of
Helicobacter pylori
and Correlation between Agar Dilution and E Test Methods
Authors: Best L. M. , Haldane D. J. M. , Keelan M. , Taylor D. E. , Thomson A. B. R. , Loo V. , Fallone C. A. , Lyn P. , Smaill F. M. , Hunt R. , Gaudreau C. , Kennedy J. , Alfa M. , Pelletier R. , Veldhuyzen van Zanten S. J. O. 
Published: September 2003

ABSTRACT

Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain
Helicobacter pylori
ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (
www.Helicobactercanada.org
). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log
2
dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log
2
dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin- and metronidazole-susceptible and -resistant strains of
H. pylori
93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.
Antifungal Susceptibility Survey of 2,000 Bloodstream
Candida
Isolates in the United States
Authors: Ostrosky-Zeichner Luis , Rex John H. , Pappas Peter G. , Hamill Richard J. , Larsen Robert A. , Horowitz Harold W. , Powderly William G. , Hyslop Newton , Kauffman Carol A. , Cleary John , Mangino Julie E. , Lee Jeannette 
Published: September 2003

ABSTRACT

Candida
bloodstream isolates (
n
= 2,000) from two multicenter clinical trials carried out by the National Institute of Allergy and Infectious Diseases Mycoses Study Group between 1995 and 1999 were tested against amphotericin B (AMB), flucytosine (5FC), fluconazole (FLU), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), caspofungin (CFG), micafungin (MFG), and anidulafungin (AFG) using the NCCLS M27-A2 microdilution method. All drugs were tested in the NCCLS-specified RPMI 1640 medium except for AMB, which was tested in antibiotic medium 3. A sample of isolates was also tested in RPMI 1640 supplemented to 2% glucose and by using the diluent polyethylene glycol (PEG) in lieu of dimethyl sulfoxide for those drugs insoluble in water. Glucose supplementation tended to elevate the MIC, whereas using PEG tended to decrease the MIC. Trailing growth occurred frequently with azoles. Isolates were generally susceptible to AMB, 5FC, and FLU. Rates of resistance to ITR approached 20%. Although no established interpretative breakpoints are available for the candins (CFG, MFG, and AFG) and the new azoles (VOR and POS), they all exhibited excellent antifungal activity, even for those strains resistant to the other aforementioned agents.
Clinical Isolates of
Streptococcus pneumoniae
with Different Susceptibilities to Ceftriaxone and Cefotaxime
Authors: Karlowsky James A. , Jones Mark E. , Draghi Deborah C. , Sahm Daniel F. 
Published: September 2003

ABSTRACT

Ceftriaxone and cefotaxime are extended-spectrum cephalosporins previously demonstrated to possess very similar in vitro activities against
Streptococcus pneumoniae
. Anecdotal reports of isolates with divergent in vitro susceptibilities to ceftriaxone and cefotaxime have been published. To determine the prevalence of pneumococcal isolates with divergent ceftriaxone and cefotaxime susceptibilities, we tested 1,000 clinical isolates collected by U.S. laboratories in 2001-2002 by broth microdilution and E-test. The percentages of isolates susceptible to ceftriaxone and cefotaxime were significantly different by both broth microdilution (98.6 and 96.6%, respectively;
P
< 0.05) and E-test (98.3 and 95.8%;
P
< 0.001). The differences observed were due solely to the activities of the two agents against penicillin-resistant isolates. Twenty-six of 188 penicillin-resistant isolates (13.8%) demonstrated different ceftriaxone and cefotaxime MIC interpretative phenotypes when tested by broth microdilution; 18 isolates were concurrently ceftriaxone susceptible and cefotaxime intermediate, 6 were ceftriaxone intermediate and cefotaxime resistant, and 2 were ceftriaxone susceptible and cefotaxime resistant (1.1% of penicillin-resistant isolates; 0.2% of all isolates tested). Sixteen of the 26 isolates (65%) were from southern U.S. states. The 26 isolates had serogroups and serotypes (6, 9, 14, 19, and 23) commonly associated with penicillin-resistant isolates;
Sma
I pulsed-field gel electrophoresis identified 18 isolates (69%) dispersed among five subtype groups and 8 isolates that were unrelated to any of the other isolates. We conclude that certain isolates of penicillin-resistant pneumococci are less susceptible to cefotaxime than to ceftriaxone and that these isolates are not the result of the spread of a single clone. Whether such isolates have increased in prevalence over time remains unknown.
In Vitro Activities of New Antifungal Agents against
Chaetomium
spp. and Inoculum Standardization
Authors: Serena Carolina , Ortoneda Montserrat , Capilla Javier , Pastor F. Javier , Sutton Deanna A. , Rinaldi Michael G. , Guarro Josep 
Published: September 2003

ABSTRACT

Chaetomium
is an unusual etiological agent of human infections, but the mortality rate among immunocompromised patients is considerably greater than that among nonimmunocompromised individuals. We investigated the in vitro antifungal susceptibilities to novel antifungal agents of 19 strains belonging to three species of
Chaetomium
which have been involved in human infections, i.e.,
Chaetomium globosum
,
C. atrobrunneum
, and
C. nigricolor
, and one strain of the closely related species
Achaetomium strumarium
. A modification of the NCCLS reference microdilution method (M38-A) was used to evaluate the in vitro activities of ravuconazole, voriconazole, albaconazole, and micafungin. Micafungin was not active at all, while the geometric mean MICs and minimum effective concentrations of the three triazoles were less than 0.5 and 0.4 μg/ml, respectively.
Cyclic AMP Signaling Pathway Modulates Susceptibility of
Candida
Species and
Saccharomyces cerevisiae
to Antifungal Azoles and Other Sterol Biosynthesis Inhibitors
Authors: Jain Pooja , Akula Indira , Edlind Thomas 
Published: September 2003

ABSTRACT

Azoles are widely used antifungals; however, their efficacy is compromised by fungistatic activity and selection of resistant strains during treatment. Recent studies demonstrated roles for the protein kinase C and calcium signaling pathways in modulating azole activity. Here we explored a role for the signaling pathway mediated by cyclic AMP (cAMP), which is synthesized by the regulated action of adenylate cyclase (encoded by
CDC35
in
Candida albicans
and
CYR1
in
Saccharomyces cerevisiae
) and cyclase-associated protein (encoded by
CAP1
and
SRV2
, respectively). Relative to wild-type strains,
C. albicans
and
S. cerevisiae
strains mutated in these genes were hypersusceptible to fluconazole (>4- to >16-fold-decreased 48-h MIC), itraconazole (>8- to >64-fold), or miconazole (16- to >64-fold). Similarly, they were hypersusceptible to terbinafine and fenpropimorph (2- to >16-fold), which, like azoles, inhibit sterol biosynthesis. Addition of cAMP to the medium at least partially reversed the hypersusceptibility of Ca-
cdc35
and Sc-
cyr1
-
2
mutants. An inhibitor of mammalian adenylate cyclase, MDL-12330A, was tested in combination with azoles; a synergistic effect was observed against azole-susceptible and -resistant strains of
C. albicans
and five of six non-
C. albicans Candida
species. Analysis of cAMP levels after glucose induction in the presence and absence of MDL-12330A confirmed that it acts by inhibiting cAMP synthesis in yeast. RNA analysis suggested that a defect in azole-dependent upregulation of the multidrug transporter gene
CDR1
contributes to the hypersusceptibility of the Ca-
cdc35
mutant. Our results implicate cAMP signaling in the yeast azole response; compounds similar to MDL-12330A may be useful adjuvants in azole therapy.
Inhibition of Gene Expression inEscherichia coliby Antisense Phosphorodiamidate Morpholino Oligomers
Authors: Geller B. L. , Deere J. D. , Stein D. A. , Kroeker A. D. , Moulton H. M. , Iversen P. L. 
Published: September 2003

ABSTRACTAntisense phosphorodiamidate morpholino oligomers (PMOs) were tested for the ability to inhibit gene expression inEscherichia coli.PMOs targeted to either a myc-luciferase reporter gene product or 16S rRNA did not inhibit luciferase expression or growth. However, in a strain with defective lipopolysaccharide (lpxAmutant), which has a leaky outer membrane, PMOs targeted to the myc-luciferase or acyl carrier protein (acpP) mRNA significantly inhibited their targets in a dose-dependent response. A significant improvement was made by covalently joining the peptide (KFF)3KC to the end of PMOs. In strains with an intact outer membrane, (KFF)3KC-myc PMO inhibited luciferase expression by 63%. A second (KFF)3KC-PMO conjugate targeted tolacImRNA induced β-galactosidase in a dose-dependent response. The end of the PMO to which (KFF)3KC is attached affected the efficiency of target inhibition but in various ways depending on the PMO. Another peptide-lacI PMO conjugate was synthesized with the cationic peptide CRRRQRRKKR and was found not to induce β-galactosidase. We conclude that the outer membrane ofE. coliinhibits entry of PMOs and that (KFF)3KC-PMO conjugates are transported across both membranes and specifically inhibit expression of their genetic targets.
Uptake of Nitrobenzylthioinosine and Purine β-
l
-Nucleosides by Intracellular
Toxoplasma gondii
Authors: Al Safarjalani Omar N. , Naguib Fardos N. M. , el Kouni Mahmoud H. 
Published: September 2003

ABSTRACT

Intracellular
Toxoplasma gondii
grown in human foreskin fibroblast cells transported nitrobenzylthioinosine {NBMPR; 6-[(4-nitrobenzyl)mercapto]-9-β-
d
-ribofuranosylpurine}, an inhibitor of nucleoside transport in mammalian cells, as well as the nonphysiological β-
l
-enantiomers of purine nucleosides, β-
l
-adenosine, β-
l
-deoxyadenosine, and β-
l
-guanosine. The β-
l
-pyrimidine nucleosides, β-
l
-uridine, β-
l
-cytidine, and β-
l
-thymidine, were not transported. The uptake of NBMPR and the nonphysiological purine nucleoside β-
l
-enantiomers by the intracellular parasites also implies that
Toxoplasma
-infected cells can transport these nucleosides. In sharp contrast, under the same conditions, uninfected fibroblast cells did not transport NBMPR or any of the unnatural β-
l
-nucleosides. β-
d
-Adenosine and dipyridamole, another inhibitor of nucleoside transport, inhibited the uptake of NBMPR and β-
l
-stereoisomers of the purine nucleosides by intracellular
Toxoplasma
and
Toxoplasma
-infected cells. Furthermore, infection with a
Toxoplasma
mutant deficient in parasite adenosine/purine nucleoside transport reduced or abolished the uptake of β-
d
-adenosine, NBMPR, and purine β-
l
-nucleosides. Hence, the presence of the
Toxoplasma
adenosine/purine nucleoside transporters is apparently essential for the uptake of NBMPR and purine β-
l
-nucleosides by intracellular
Toxoplasma
and
Toxoplasma
-infected cells. These results also demonstrate that, in contrast to the mammalian nucleoside transporters, the
Toxoplasma
adenosine/purine nucleoside transporter(s) lacks stereospecificity and substrate specificity in the transport of purine nucleosides. In addition, infection with
T. gondii
confers the properties of the parasite's purine nucleoside transport on the parasitized host cells and enables the infected cells to transport purine nucleosides that were not transported by uninfected cells. These unique characteristics of purine nucleoside transport in
T. gondii
may aid in the identification of new promising antitoxoplasmic drugs.