bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving oral healthcare: improving the quality of life for patients after a stroke
Authors: Tran Phuong , Mannen Jana 
Published: August 2009

ABSTRACTWith the increase in the elderly population, the prevalence of systemic diseases such as strokes and heart attacks will also increase. Persons who have had a stroke will be more susceptible to mistreatment, neglect, abuse, and aspiration pneumonia. The expansion of the elderly population will make the training of professional healthcare workers and other auxiliaries extremely important. Quality of life can be maintained if poor oral health is reduced through better daily oral hygiene practices. Informing others about the known association between oral health and systemic diseases will increase the awareness of the need for good oral hygiene in order to reduce the risk of systemic diseases. Healthcare professionals must also be able to recognize, document, and report to Adult Protective Services suspected abuse such as physical and dental neglect. The networking of healthcare providers with Adult Protective Services and other professional disciplines will provide a collaborative approach to assure successful integration of healthcare protocols for the elderly population.
β‐Defensin 1 haplotype associated with postoperative endophthalmitis
Authors: Carter James G. , West Stephanie K. , Painter Sally , Haynes Richard J. , Churchill Amanda J. 
Published: August 2009

Acta Ophthalmol. 2010: 88: 786–790Abstract.Purpose:  Endophthalmitis is a rare but sight‐threatening complication of intraocular surgery. β‐Defensins are antimicrobial peptides that appear to be important components of the ocular immune response. We propose that variation in defensin genes may alter susceptibility to endophthalmitis.Methods:  Post‐cataract endophthalmitis patients (n = 28) and post‐cataract controls (n = 75) were recruited and DNA samples extracted. The β‐defensin 1 gene (DEFB1) was screened for single‐nucleotide polymorphisms (SNPs) using bidirectional sequencing. Case–control statistical assessment was undertaken for both the individual polymorphic loci observed and combined haplotypes using PHASE software.Results:  We identified 19 SNPs and observed strong linkage disequilibrium within the gene. We found that the three‐SNP haplotype −688C/−44C/−20A was associated strongly with endophthalmitis [odds ratio (OR) = 8.88 (1.74, 45.42), corrected p = 0.0095]. Furthermore, we uncovered several trends, including increased prevalence of the −44CC genotype in the endophthalmitis group.Conclusion:  We have shown previously that the −44CC SNP genotype was present in a single case of bilateral endophthalmitis. In this study, we found this genotype to be more common in the endophthalmitis group and a mini‐haplotype including this SNP was associated strongly with endophthalmitis. There is functional evidence that this genetic profile decreases transcription of the β‐defensin 1 peptide and could therefore reduce the innate ocular immune defence.
Ocular blood flow and oxygen delivery to the retina in primary open‐angle glaucoma patients: the addition of dorzolamide to timolol monotherapy
Authors: Siesky Brent , Harris Alon , Kagemann Larry , Stefansson Einar , McCranor Lynne , Miller Brian , Bwatwa Jeremiah , Regev Guy , Ehrlich Rita 
Published: August 2009

AbstractPurpose:  To assess the effects of adding dorzolamide to timolol monotherapy on ocular haemodynamics and retinal oxygen saturation in patients with primary open‐angle glaucoma (POAG).Methods:  Twenty‐four patients (12 healthy, 12 with POAG) were treated with dorzolamide/timolol combination (DT) versus timolol maleate 0.5% twice daily in a randomized, crossover, double‐blind study conducted over a period of 18 months. Patients received each treatment for 8 months then crossed over to the other treatment after a 1‐month washout and second baseline. Goldmann applanation tonometry, Heidelberg retinal flowmetry (HRF), colour Doppler imaging (CDI) and retinal photographic oximetry were performed at each visit.Results:  DT significantly reduced intraocular pressure (IOP) in both glaucomatous [right eye (OD) −13.15%, left eye (OS) −14.43%; p < 0.036] and non‐glaucomatous (OD −12.4%, OS −13.88%; p < 0.039) patients compared to timolol after 8 months of treatment. DT significantly reduced the number of zero blood flow pixels in the superior (−39.72%; p < 0.014) and inferior (−51.44%; p < 0.008) retina in the non‐glaucomatous group and inferior retina in the glaucomatous group (−55.38%, p < 0.006). The continuation of timolol monotherapy from baseline did not change (p < 0.05) any measured parameter and neither treatment had a significant effect (p < 0.05) on retinal oximetry or CDI parameters.Conclusion:  The addition of dorzolamide to timolol monotherapy decreases IOP and increases retinal blood flow in the superficial retinal vasculature in both glaucomatous and healthy patients following 8 months of treatment. The combination of increased retinal blood flow with consistent oxygen saturation may potentially increase oxygen delivery to the retina.
Comparison of Methods To Test Antibiotic Combinations against Heterogeneous Populations of Multiresistant
Pseudomonas aeruginosa
from Patients with Acute Infective Exacerbations in Cystic Fibrosis
Authors: Foweraker Juliet E. , Laughton Christian R. , Brown Derek F. , Bilton Diana 
Published: August 2009

ABSTRACT

Multiresistant
Pseudomonas aeruginosa
isolates can chronically infect patients with cystic fibrosis. Acute infective exacerbations are treated with combinations of two antipseudomonal antibiotics. Patients may respond clinically even if the bacteria are resistant, possibly due to antimicrobial synergy. The challenge for testing for synergy in vitro is that there is no standardized method, and the antibiotic susceptibility in a population of
P. aeruginosa
isolates in a single sputum sample can vary. We therefore compared (i) antibiotic combinations with different examples of resistant bacteria from the same sputum sample and (ii) the results of synergy testing by different methods. Antibiotic synergy was tested by using resistant
P. aeruginosa
isolates recovered from sputum samples taken just before the start of treatment for an acute infective exacerbation. Several examples of each morphotype of
P. aeruginosa
were tested by cidal checkerboard, time-kill curve, and multiple-combination bactericidal testing. The isolates were typed by pulsed-field gel electrophoresis (PFGE). The results were compared with the clinical and microbiological responses to 14 days of antibiotic treatment. Forty-four resistant isolates from nine patients were tested. Some
P. aeruginosa
isolates with the same morphotype and PFGE pulsotype had different results by synergy testing. There was a poor correlation between the results of the different methods of synergy testing, and no one method would have predicted the response to treatment in all patients. The in vitro effects of antibiotic combinations against different isolates from the same sputum sample can vary, and the results depend on the methodology used. The role of combination testing for the treatment of antibiotic-resistant
P. aeruginosa
in acute exacerbations of chronic infection in patients with cystic fibrosis needs to be reviewed.
Penetration of Colistin into Cerebrospinal Fluid
Authors: Markantonis S. L. , Markou N. , Fousteri M. , Sakellaridis N. , Karatzas S. , Alamanos I. , Dimopoulou E. , Baltopoulos G. 
Published: August 2009

ABSTRACT
Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with the exception of one patient with an external ventriculostomy. CSF-to-serum ratios (0.051 to 0.057) for all study patients coincided at all sampling times. The low level (5%) of penetration suggests inadequate bactericidal colistin concentrations in the CSF.
Tooth-Binding Micelles for Dental Caries Prevention
Authors: Chen Fu , Liu Xin-Ming , Rice Kelly C. , Li Xue , Yu Fang , Reinhardt Richard A. , Bayles Kenneth W. , Wang Dong 
Published: August 2009

ABSTRACTMaintenance of the effective local concentration of antimicrobials on the tooth surface is critical for the management of cariogenic bacteria in the oral cavity. We report on the design of a simple tooth-binding micellar drug delivery platform that would effectively bind to tooth surfaces. To achieve tooth-binding ability, the chain termini of biocompatible Pluronic copolymers were modified with a biomineral-binding moiety (i.e., alendronate). The micelles formulated with this polymer were shown to be able to swiftly (<1 min) bind to hydroxyapatite (HA; a model tooth surface) and gradually release the encapsulated model antimicrobial (farnesol). These tooth-binding micelles were negatively charged and had an average effective hydrodynamic diameter of less than 100 nm. In vitro biofilm inhibition studies demonstrated that the farnesol-containing tooth-binding micelles were able to provide significantly stronger inhibition ofStreptococcus mutansUA159 biofilm formation on HA discs than the untreated blank control micelles (P< 0.0001). Upon further optimization, this delivery platform could provide an effective tool for caries prevention and treatment.
IS
CR2
, Another Vehicle for
bla
VEB
Gene Acquisition
Authors: Poirel Laurent , Mugnier Pauline D. , Toleman Mark A. , Walsh Timothy R. , Rapoport Melina J. , Petroni Alejandro , Nordmann Patrice 
Published: August 2009

ABSTRACT

The expanded-spectrum β-lactamase (ESBL) gene
bla
VEB-1
, identified worldwide in
Enterobacteriaceae
and
Pseudomonas aeruginosa
, is associated with either class 1 integrons or repeated elements. We report here the first association of
bla
VEB-1a
with the insertion sequence IS
CR2
in six
Acinetobacter
species isolates recovered from Argentina. That genetic structure was likely at the origin of the mobilization of this ESBL gene.
A Ser29Leu Substitution in the Cytosine Deaminase Fca1p Is Responsible for Clade-Specific Flucytosine Resistance in
Candida dubliniensis
Authors: McManus Brenda A. , Moran Gary P. , Higgins Judy A. , Sullivan Derek J. , Coleman David C. 
Published: August 2009

ABSTRACT

The population structure of the opportunistic yeast pathogen
Candida dubliniensis
is composed of three main multilocus sequence typing clades (clades C1 to C3), and clade C3 predominantly consists of isolates from the Middle East that exhibit high-level resistance (MIC
50
≥ 128 μg/ml) to the fungicidal agent flucytosine (5FC). The close relative of
C. dubliniensis
,
C. albicans
, also exhibits clade-specific resistance to 5FC, and resistance is most commonly mediated by an Arg101Cys substitution in the
FUR1
gene encoding uracil phosphoribosyltransferase. Broth microdilution assays with fluorouracil (5FU), the toxic deaminated form of 5FC, showed that both 5FC-resistant and 5FC-susceptible
C. dubliniensis
isolates exhibited similar 5FU MICs, suggesting that the
C. dubliniensis
cytosine deaminase (Fca1p) encoded by
C. dubliniensis FCA1
(Cd
FCA1
) may play a role in mediating
C. dubliniensis
clade-specific 5FC resistance. Amino acid sequence analysis of the Cd
FCA1
open reading frame (ORF) identified a homozygous Ser29Leu substitution in all 12 5FC-resistant isolates investigated which was not present in any of the 9 5FC-susceptible isolates examined. The tetracycline-inducible expression of the Cd
FCA1
ORF from a 5FC-susceptible
C. dubliniensis
isolate in two separate 5FC-resistant clade C3 isolates restored susceptibility to 5FC, demonstrating that the Ser29Leu substitution was responsible for the clade-specific 5FC resistance and that the 5FC resistance encoded by
FCA1
genes with the Ser29Leu transition is recessive. Quantitative real-time PCR analysis showed no significant difference in Cd
FCA1
expression between 5FC-susceptible and 5FC-resistant isolates in either the presence or the absence of subinhibitory concentrations of 5FC, suggesting that the Ser29Leu substitution in the Cd
FCA1
ORF is the sole cause of 5FC resistance in clade C3
C. dubliniensis
isolates.
New Approach for Drug Susceptibility Testing: Monitoring the Stress Response of Mycobacteria
Authors: Rieder Ronald J. , Zhao Zhihui , Zavizion Boris 
Published: August 2009

ABSTRACT

Methods currently used for in vitro drug susceptibility testing are based on the assessment of bacterial growth-related processes. This reliance on cellular reproduction leads to prolonged incubation times, particularly for slowly growing organisms such as mycobacteria. A new rapid phenotypic method for the drug susceptibility testing of mycobacteria is described. The method is based on the detection of the physiological stress developed by susceptible mycobacterial cells in the presence of an antimicrobial compound. The induced stress was quantified by differential monitoring of the dielectric properties of the bacterial suspension, an easily measurable electronic property. The data presented here characterize the stress developed by
Mycobacterium tuberculosis
cells treated with rifampin (rifampicin), isoniazid, ethambutol, and pyrazinamide. Changes in the dielectric-based profiles of the drug-treated bacteria revealed the respective susceptibilities in near real time, and the susceptibilities were well correlated with conventional susceptibility test data.
Pulmonary Epithelial Lining Fluid Concentrations after Use of Systemic Amphotericin B Lipid Formulations
Authors: Weiler Stefan , Falkensammer Gerda , Hammerer-Lercher Angelika , Anliker Markus , Vogelsinger Helene , Joannidis Michael , Dunzendorfer Stefan , Stein Markus , Bellmann Romuald 
Published: August 2009

ABSTRACT

Amphotericin B (AMB) concentrations were determined in pulmonary epithelial lining fluid (ELF) of 44 critically ill patients, who were receiving treatment with liposomal AMB (LAMB) (
n
= 11), AMB colloidal dispersion (ABCD) (
n
= 28), or AMB lipid complex (ABLC) (
n
= 5). Mean AMB levels (± standard errors of the means) in ELF amounted to 1.60 ± 0.58, 0.38 ± 0.07, and 1.29 ± 0.71 μg/ml in LAMB-, ABCD-, and ABLC-treated patients, respectively (differences are not significant).
Radiolabeled Antibodies to
Bacillus anthracis
Toxins Are Bactericidal and Partially Therapeutic in Experimental Murine Anthrax
Authors: Rivera Johanna , Nakouzi Antonio S. , Morgenstern Alfred , Bruchertseifer Frank , Dadachova Ekaterina , Casadevall Arturo 
Published: August 2009

ABSTRACT

Bacillus anthracis
is a powerful agent for use in biological warfare, and infection with the organism is associated with a high rate of mortality, underscoring the need for additional effective therapies for anthrax. Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver a microbicidal radioactive nuclide to a site of infection. RIT has proven therapeutic in experimental models of viral, bacterial, and fungal infections; but it is not known whether this approach can successfully employ toxin binding monoclonal antibodies (MAbs) for diseases caused by toxigenic bacteria. Indirect immunofluorescence studies with MAbs to protective antigen (MAbs 7.5G γ2b and 10F4 γ1) and lethal factor (MAb 14FA γ2b) revealed the surface expression of toxins on bacterial cells. Scatchard analysis of MAbs revealed high binding constants and numerous binding sites on the bacterial surface. To investigate the microbicidal properties of these MAbs, our group radiolabeled MAbs with either
188
Re or
213
Bi. In vitro,
213
Bi was more efficient than
188
Re in mediating microbicidal activity against
B. anthracis
. The administration of MAbs [
213
Bi]10F4 γ1 and [
213
Bi]14FA γ2b prolonged the survival of A/JCr mice infected with
B. anthracis
Sterne bacterial cells but not
B. anthracis
Sterne spores. These results indicate that RIT with MAbs that target
B. anthracis
toxin components can be used to treat experimental anthrax infection and suggest that toxigenic bacteria may be targeted with radiolabeled MAbs.
Kinetics of the Natural, Humoral Immune Response toSalmonella entericaSerovar Typhi in Kathmandu, Nepal
Authors: Pulickal Anoop S. , Gautam Samir , Clutterbuck Elizabeth A. , Thorson Stephen , Basynat Buddha , Adhikari Neelam , Makepeace Katherine , Rijpkema Sjoerd , Borrow Ray , Farrar Jeremy J. , Pollard Andrew J. 
Published: August 2009

ABSTRACTTyphoid fever is a major public health problem in developing countries, conservatively estimated to occur in 17 million cases and be responsible for 200,000 deaths annually. We investigated the acquisition of natural immunity toSalmonella entericaserovar Typhi in a region where typhoid is endemic by testing sera from an age-stratified sample of 210 healthy participants in Kathmandu, Nepal, for bactericidal activity towardS. Typhi and for anti-Vi capsular polysaccharide antibodies. Bactericidal titers in children were significantly lower than those in newborns and adults (P< 0.0001). Anti-S. Typhi bactericidal geometric mean titers were age dependent, increasing 10-fold during childhood. Anti-Vi polysaccharide antibody geometric mean concentrations were also lower in children than in adults. Data presented here indicate the possibility of a relationship between low levels of bactericidal activity towardS. Typhi in serum and susceptibility to disease, as observed for other polysaccharide-encapsulated bacteria. Bactericidal antibody may be a marker of protective immunity againstS. Typhi.
Nondividing but Metabolically Active Gamma-IrradiatedBrucella melitensisIs Protective against VirulentB. melitensisChallenge in Mice
Authors: Magnani D. M. , Harms J. S. , Durward M. A. , Splitter G. A. 
Published: August 2009

ABSTRACTBrucellaspp. are gram-negative bacteria that cause the most frequent zoonotic disease worldwide, with more than 500,000 human infections yearly; however, no human vaccine is currently available. As with other intracellular organisms, cytotoxic mechanisms against infected cells are thought to have an important role in controlling infection and mediating long-term immunity. Live attenuated strains developed for use in animals elicit protection but retain unacceptable levels of virulence. Thus, the optimal design for a brucellosis vaccine requires a nonliving vaccine that confers effective immunity. Historically, inactivation methods such as chemical or heat treatment successfully impairBrucellareproductive capacity; nevertheless, metabolically inactive vaccines (subunit or killed) present very limited efficacy. Hence, we hypothesized that bacterial metabolism plays a major role in creating the proper antigenic and adjuvant properties required for efficient triggering of protective responses. Here, we demonstrate that inactivation ofBrucella melitensisby gamma-irradiation inhibited its replication capability and yet retained live-Brucellaprotective features. IrradiatedBrucellapossessed metabolic and transcriptional activity, persisted in macrophages, generated antigen-specific cytotoxic T cells, and protected mice against virulent bacterial challenge, without signs of residual virulence. In conclusion, pathogen metabolic activity has a positive role in shaping protective responses, and the generation of inactivated and yet metabolically active microbes is a promising strategy for safely vaccinating against intracellular organisms such asB. melitensis.
Francisella tularensis
Induces Extensive Caspase-3 Activation and Apoptotic Cell Death in the Tissues of Infected Mice
Authors: Wickstrum Jason R. , Bokhari Sirosh M. , Fischer Jeffrey L. , Pinson David M. , Yeh Hung-Wen , Horvat Rebecca T. , Parmely Michael J. 
Published: August 2009

ABSTRACT

Although
Francisella tularensis
subsp.
tularensis
is known to cause extensive tissue necrosis, the pathogenesis of tissue injury has not been elucidated. To characterize cell death in tularemia, C57BL/6 mice were challenged by the intranasal route with type A
F. tularensis
, and the pathological changes in infected tissues were characterized over the next 4 days. At 3 days postinfection, well-organized inflammatory infiltrates developed in the spleen and liver following the spread of infection from the lungs. By the next day, extensive cell death, characterized by the presence of pyknotic cells containing double-strand DNA breaks, was apparent throughout these inflammatory foci. Cell death was not mediated by activated caspase-1, as has been reported for cells infected with other
Francisella
subspecies. Mouse macrophages and dendritic cells that had been stimulated with type A
F. tularensis
did not release interleukin-18 in vitro, a response that requires the activation of procaspase-1. Dying cells within type A
F. tularensis
-infected tissues expressed activated caspase-3 but very little activated caspase-1. When caspase-1-deficient mice were challenged with type A
F. tularensis
, pathological changes, including extensive cell death, were similar to those seen in infected wild-type mice. In contrast, type A
F. tularensis
-infected caspase-3-deficient mice showed much less death among their F4/80
+
spleen cells than did infected wild-type mice, and they retained the ability to express tumor necrosis factor alpha and inducible NO synthase. These findings suggest that type A
F. tularensis
induces caspase-3-dependent macrophage apoptosis, resulting in the loss of potentially important innate immune responses to the pathogen.
Mouse Eosinophils Possess Potent Antibacterial Properties In Vivo
Authors: Linch Stefanie N. , Kelly Ann M. , Danielson Erin T. , Pero Ralph , Lee James J. , Gold Jeffrey A. 
Published: August 2009

ABSTRACTEosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils, suggesting that these leukocytes may participate in the recognition and killing of viruses and bacteria. However, the significance of this role in the innate immune response to bacterial infection is largely unknown. Here we report a novel role for eosinophils as antibacterial defenders in the host response. Isolated mouse eosinophils possessed antipseudomonal properties in vitro. In vivo, interleukin-5 transgenic mice, which have profound eosinophilia, demonstrated improved clearance ofPseudomonas aeruginosaintroduced into the peritoneal cavity. The findings of improved bacterial clearance following adoptive transfer of eosinophils, and impaired bacterial clearance in mice with a congenital eosinophil deficiency, established that this effect was eosinophil specific. The data presented also demonstrate that eosinophils mediate this antibacterial effect in part through the release of cationic secondary granule proteins. Specifically, isolated eosinophil granules had antibacterial properties in vitro, and administration of eosinophil granule extracts significantly improved bacterial clearance in vivo. These data suggest a potent yet underappreciated antibacterial role for eosinophils in vivo, specifically for eosinophil granules. Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.