bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Characterization of Heterogeneous Resistance to Imipenem in Invasive Nontypeable
Haemophilus influenzae
Isolates
Authors: Cerquetti Marina , Giufrè Maria , Cardines Rita , Mastrantonio Paola 
Published: July 2007

ABSTRACT

This study describes the first two reported invasive nontypeable
Haemophilus influenzae
(NTHI) isolates (strains 183 and 184) with heterogeneous resistance to imipenem. For both isolates, Etest showed imipenem MICs of ≥32 μg/ml. When the two strains were examined by the quantitative method of population analysis, both strain populations were heterogeneously resistant to imipenem and contained subpopulations growing in the presence of up to 32 μg of imipenem/ml at frequencies of 1.7 × 10
−5
and 1.5 × 10
−7
, respectively. By pulsed-field gel electrophoresis analysis, the two isolates appeared to be genetically closely related. The sequencing of the
ftsI
gene encoding penicillin-binding protein 3 (PBP 3) and comparison with the sequence of the imipenem-susceptible
H. influenzae
strain Rd identified a pattern of six amino acid substitutions shared between strains 183 and 184; an additional change was unique to strain 183. No relationship between mutations in the
dacB
gene encoding PBP 4 and imipenem resistance was found. The replacement of the
ftsI
gene in the imipenem-susceptible strain Rd (for which the MIC of imipenem is 0.38 to 1 μg/ml) with
ftsI
from strain 183 resulted in a transformant for which the MIC of imipenem ranged from 4 to 8 μg/ml as determined by Etest. The Rd/183 transformant population showed heterogeneous resistance to imipenem; it contained subpopulations growing in the presence of up to 32 μg of imipenem/ml at a frequency of 3.3 ×10
−8
. The presence of additional resistance mechanisms, such as the overexpression of the AcrAB efflux pump, was investigated and does not seem to be involved. These data indicate that the heterogeneous imipenem resistance phenotype of our NTHI clone depends largely on the PBP 3 amino acid substitutions. We speculated that bacterial regulatory networks may play a role in the control of the heterogeneous expression of the resistance phenotype.
Population Pharmacokinetics and Pharmacodynamics of Continuous versus Short-Term Infusion of Imipenem-Cilastatin in Critically Ill Patients in a Randomized, Controlled Trial
Authors: Sakka Samir G. , Glauner Anna K. , Bulitta Jürgen B. , Kinzig-Schippers Martina , Pfister Wolfgang , Drusano George L. , Sörgel Fritz 
Published: July 2007

ABSTRACTBeta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT>MIC) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by thefT>MICvalue of imipenem. In this prospective, randomized, controlled clinical study, patients received either a loading dose of 1 g/1 g imipenem and cilastatin (as a short-term infusion) at time zero, followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days (n= 10), or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days (total daily dose, 3 g/3 g;n= 10). Imipenem concentrations in plasma were determined by using a validated liquid chromatography-tandem mass spectrometry assay. A two-compartment open model was employed for population pharmacokinetic modeling. We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40%fT>MIC. The probability of target attainment by MIC for intermittent infusion was robust (>90%) up to MICs of 1 to 2 mg/liter. The corresponding value for continuous infusion was 2 to 4 mg/liter. Although all 20 patients had anfT>MICof 100%, 3 patients died. Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis. Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients.
Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo
Authors: Cai Xun-Zi , Yan Shi-Gui , Wu Hao-Bo , He Rong-Xin , Dai Xue-Song , Chen Hai-Xiang , Yan Rui-Jian , Zhao Xin-Hua 
Published: July 2007

ABSTRACT

This study sought to investigate the effect of delayed pulsed-wave ultrasound with low frequency on drug release from and the antimicrobial efficacy of vancomycin-loaded acrylic bone cement in vivo and the possible mechanism of this effect. After the implantation of cement and the inoculation of
Staphylococcus aureus
into the bilateral hips of rabbits, ultrasound (average intensity, 300 mW/cm
2
; frequency, 46.5 kHz; on/off ratio, 20 min/10 min) was applied to animals in the normal ultrasound group (UG
0-12
) from 0 through 12 h after surgery and to those in the delayed-ultrasound group (UG
12-24
) from 12 through 24 h after surgery. The control group (CG) was not exposed to ultrasound. Based on vancomycin concentrations in left hip cavities at projected time intervals, the amount of time during which the local drug concentration exceeded the MIC (
T
>MIC
) in UG
12-24
was significantly prolonged compared with that in either CG or UG
0-12
, and the ratios between the areas under the concentration-time curves over 24 h and the MIC for UG
0-12
and UG
12-24
were both increased compared with that for CG. The greatest reductions in bacterial densities in both right hip aspirates and right femoral tissues at 48 h were achieved with UG
12-24
. Local hemorrhage in rabbits of UG
0-12
during the 12-h insonation was more severe than that in rabbits of UG
12-24
. Of four variables, the
T
>MIC
and the bioacoustic effect were both identified as parameters predictive of the enhancement of the antimicrobial efficacy of cement by ultrasound. Sustained concentrations above the MIC replaced early high maximum concentrations and long-term subtherapeutic release of the drug, provided that ultrasound was not applied until local hemorrhage was relieved. The enhancement of the antimicrobial efficacy of cement by ultrasound may be attributed to the prolonged
T
>MIC
and the bioacoustic effect caused by ultrasound.
Activity of Colistin against Heteroresistant
Acinetobacter baumannii
and Emergence of Resistance in an In Vitro Pharmacokinetic/Pharmacodynamic Model
Authors: Tan Chun-Hong , Li Jian , Nation Roger L. 
Published: July 2007

ABSTRACT

Three clinically relevant intermittent regimens, and a continuous infusion, of colistin were simulated in an in vitro pharmacokinetic/pharmacodynamic model against two colistin-heteroresistant strains of
Acinetobacter baumannii
. Extensive initial killing was followed by regrowth as early as 6 h later; bacterial density in the 24- to 72-h period was within 1 log
10
CFU/ml of growth control. Population analysis profiles revealed extensive emergence of resistant subpopulations regardless of the colistin regimen.
Slc11a1, Formerly Nramp1, Is Expressed in Dendritic Cells and Influences Major Histocompatibility Complex Class II Expression and Antigen-Presenting Cell Function
Authors: Stober Carmel B. , Brode Sven , White Jacqueline K. , Popoff Jean-François , Blackwell Jenefer M. 
Published: July 2007

ABSTRACTSolute carrier family 11 member a1 (Slc11a1; formerlyNramp1) encodes a late endosomal/lysosomal protein/divalent cation transporter that regulates iron homeostasis in macrophages. During macrophage activation, Slc11a1 has multiple pleiotropic effects on gene regulation and function, including gamma interferon-induced class II expression and antigen-presenting cell function. The wild-type allele atSlc11a1has been associated with a bias in Th1 cell function in vivo, which is beneficial in resistance to infection against intracellular macrophage pathogens but detrimental in contributing to development of type 1 diabetes. The extent to which this depends on macrophage versus dendritic cell (DC) function is not known. Here we show that Slc11a1 is expressed in late endosomes and/or lysosomes of CD11c+DCs. DCs from mutant and congenic wild-type mice upregulate interleukin-12 (IL-12) and IL-10 mRNA in response to lipopolysaccharide (LPS) stimulation, but the ratio of IL-10 to IL-12 is higher in unstimulated DCs and DCs stimulated for 15 h with LPS from mutant mice than from wild-type mice. DCs from wild-type mice upregulate major histocompatibility complex class II in response to LPS more efficiently than DCs from mutant mice. Unstimulated DCs from wild-type and mutant mice present ovalbumin (OVA) peptide with an efficiency equivalent to that of an OVA-specific CD4 T-cell line, but DCs from wild-type mice are more efficient at processing and presenting OVA orLeishmaniaactivator of cell kinase (LACK) protein to OVA- and LACK-specific T cells. These data indicate that wild-type Slc11a1 expressed in DCs may play a role both in determining resistance to infectious disease and in susceptibility to autoimmune disease such as type 1 diabetes.
Contribution of a Novel Gene,
rpeA
, Encoding a Putative Autotransporter Adhesin to Intestinal Colonization by Rabbit-Specific Enteropathogenic
Escherichia coli
Authors: Leyton Denisse L. , Adams Louise M. , Kelly Michelle , Sloan Joan , Tauschek Marija , Robins-Browne Roy M. , Hartland Elizabeth L. 
Published: July 2007

ABSTRACT

Rabbit-specific enteropathogenic
Escherichia coli
(REPEC) is an attaching and effacing pathogen of young rabbits. Using signature-tagged mutagenesis, we identified several known colonization factors of REPEC as well as a gene predicted to encode a novel autotransporter protein. This novel gene was termed
rpeA
for
R
EPEC
p
lasmid-
e
ncoded
a
utotransporter.
Influence of the Cpx Extracytoplasmic-Stress-Responsive Pathway on
Yersinia
sp.-Eukaryotic Cell Contact
Authors: Carlsson Katrin E. , Liu Junfa , Edqvist Petra J. , Francis Matthew S. 
Published: July 2007

ABSTRACT

The extracytoplasmic-stress-responsive CpxRA two-component signal transduction pathway allows bacteria to adapt to growth in extreme environments. It controls the production of periplasmic protein folding and degradation factors, which aids in the biogenesis of multicomponent virulence determinants that span the bacterial envelope. This is true of the
Yersinia pseudotuberculosis
Ysc-Yop type III secretion system. However, despite using a second-site suppressor mutation to restore Yop effector secretion by yersiniae defective in the CpxA sensor kinase, these bacteria poorly translocated Yops into target eukaryotic cells. Investigation of this phenotype herein revealed that the expression of genes which encode several surface-located adhesins is also influenced by the Cpx pathway. In particular, the expression and surface localization of invasin, an adhesin that engages β1-integrins on the eukaryotic cell surface, are severely restricted by the removal of CpxA. This reduces bacterial association with eukaryotic cells, which could be suppressed by the ectopic production of CpxA, invasin, or RovA, a positive activator of
inv
expression. In turn, these infected eukaryotic cells then became susceptible to intoxication by translocated Yop effectors. In contrast, bacteria harboring an in-frame deletion of
cpxR
, which encodes the cognate response regulator, displayed an enhanced ability to interact with cell monolayers, as well as elevated
inv
and
rovA
transcription. This phenotype could be drastically suppressed by providing a wild-type copy of
cpxR
in
trans
. We propose a mechanism of
inv
regulation influenced by the direct negative effects of phosphorylated CpxR on
inv
and
rovA
transcription. In this fashion, sensing of extracytoplasmic stress by CpxAR contributes to productive
Yersinia
sp.-eukaryotic cell interactions.
Self-rescue swimming in cold water: the latest advice
Authors: Ducharme Michel B. , Lounsbury David S. 
Published: July 2007

According to the 2006 Canadian Red Cross Drowning Report, 2007 persons died of cold-water immersion in Canada between 1991 and 2000. These statistics indicate that prevention of cold-water immersion fatalities is a significant public health issue for Canadians. What should a person do after accidental immersion in cold water? For a long time, aquatic safety organizations and government agencies stated that swimming should not be attempted, even when a personal flotation device (PFD) is worn. The objective of the present paper is to present the recent scientific evidence making swimming a viable option for self-rescue during accidental cold-water immersion. Early studies in the 1960s and 1970s led to a general conclusion that “people are better off if they float still in lifejackets or hang on to wreckage and do not swim about to try to keep warm”. Recent evidence from the literature shows that the initial factors identified as being responsible for swimming failure can be either easily overcome or are not likely the primary contributors to swimming failure. Studies over the last decade reported that swimming failure might primarily be related not to general hypothermia, but rather to muscle fatigue of the arms as a consequence of arm cooling. This is based on the general observation that swimming failure developed earlier than did systemic hypothermia, and can be related to low temperature of the arm muscles following swimming in cold water. All of the above studies conducted in water between 10 and 14 °C indicate that people can swim in cold water for a distance ranging between about 800 and 1500 m before being incapacitated by the cold. The average swimming duration for the studies was about 47 min before incapacitation, regardless of the swimming ability of the subjects. Recent evidence shows that people have a very accurate idea about how long it will take them to achieve a given swimming goal despite a 3-fold overestimation of the absolute distance to swim. The subjects were quite astute at deciding their swimming strategy early in the immersion with 86% success, but after about 30 min of swimming or passive cooling, their decision-making ability became impaired. It would therefore seem wise to make one’s accidental immersion survival plan early during the immersion, directly after cessation of the cold shock responses. Additional recommendations for self-rescue are provided based on recent scientific evidence.
Development of Multiscale Biological Image Data Analysis: Review of 2006 International Workshop on Multiscale Biological Imaging, Data Mining and Informatics, Santa Barbara, USA (BII06)
Authors: Auer Manfred , Peng Hanchuan , Singh Ambuj 
Published: July 2007

Abstract
The 2006 International Workshop on Multiscale Biological Imaging, Data Mining and Informatics was held at Santa Barbara, on Sept 7–8, 2006. Based on the presentations at the workshop, we selected and compiled this collection of research articles related to novel algorithms and enabling techniques for bio- and biomedical image analysis, mining, visualization, and biology applications.
Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
Authors: Xiong Fu , Xiao Shaobo , Yu Meijuan , Li Wanyi , Zheng Hui , Shang Yanchang , Peng Funing , Zhao Cuiping , Zhou Wenliang , Chen Huanchun , Fang Liurong , Chamberlain Jeffrey S , Zhang Cheng 
Published: July 2007

Abstract

Background
Duchenne musclar dystrophy (DMD) is an X-linked recessive disease caused by mutations of dystrophin gene, there is no effective treatment for this disorder at present. Plasmid-mediated gene therapy is a promising therapeutical approach for the treatment of DMD. One of the major issues with plasmid-mediated gene therapy for DMD is poor transfection efficiency and distribution. The herpes simplex virus protein VP22 has the capacity to spread from a primary transduced cell to surrounding cells and improve the outcome of gene transfer. To improve the efficiency of plasmid-mediated gene therapy and investigate the utility of the intercellular trafficking properties of VP22-linked protein for the treatment for DMD, expression vectors for C-terminal versions of VP22-microdystrophin fusion protein was constructed and the VP22-mediated shuttle effect was evaluated both in vitro and in vivo.

Results
Our results clearly demonstrate that the VP22-microdystrophin fusion protein could transport into C2C12 cells from 3T3 cells, moreover, the VP22-microdystrophin fusion protein enhanced greatly the amount of microdystrophin that accumulated following microdystrophin gene transfer in both transfected 3T3 cells and in the muscles of dystrophin-deficient (mdx) mice.

Conclusion
These results highlight the efficiency of the VP22-mediated intercellular protein delivery for potential therapy of DMD and suggested that protein transduction may be a potential and versatile tool to enhance the effects of gene delivery for somatic gene therapy of DMD.
Low enrolment in Ugandan Community Health Insurance Schemes: underlying causes and policy implications
Authors: Basaza Robert , Criel Bart , Van der Stuyft Patrick 
Published: July 2007

Abstract
Background
Despite the promotion of Community Health Insurance (CHI) in Uganda in the second half of the 90's, mainly under the impetus of external aid organisations, overall membership has remained low. Today, some 30,000 persons are enrolled in about a dozen different schemes located in Central and Southern Uganda. Moreover, most of these schemes were created some 10 years ago but since then, only one or two new schemes have been launched. The dynamic of CHI has apparently come to a halt.

Methods
A case study evaluation was carried out on two selected CHI schemes: the Ishaka and the Save for Health Uganda (SHU) schemes. The objective of this evaluation was to explore the reasons for the limited success of CHI. The evaluation involved review of the schemes' records, key informant interviews and exit polls with both insured and non-insured patients.

Results
Our research points to a series of not mutually exclusive explanations for this under-achievement at both the demand and the supply side of health care delivery. On the demand side, the following elements have been identified: lack of basic information on the scheme's design and operation, limited understanding of the principles underlying CHI, limited community involvement and lack of trust in the management of the schemes, and, last but not least, problems in people's ability to pay the insurance premiums. On the supply-side, we have identified the following explanations: limited interest and knowledge of health care providers and managers of CHI, and the absence of a coherent policy framework for the development of CHI.

Conclusion
The policy implications of this study refer to the need for the government to provide the necessary legislative, technical and regulative support to CHI development. The main policy challenge however is the need to reconcile the government of Uganda's interest in promoting CHI with the current policy of abolition of user fees in public facilities.
Plasma lyso-phosphatidylcholine concentration is decreased in cancer patients with weight loss and activated inflammatory status
Authors: Taylor Lenka A. , Arends Jann , Hodina Arwen K. , Unger Clemens , Massing Ulrich 
Published: July 2007

Abstract

Background
It has been observed that ras-transformed cell lines in culture have a higher phosphatidylcholine (PC) biosynthesis rate as well as higher PC-degradation rate (increased PC-turnover) than normal cells. In correspondence to these findings, the concentrations of the PC-degradation product lyso-phosphatidylcholine (LPC) in cancer patients were found to be decreased. Our objective was the systematic investigation of the relationship between LPC and inflammatory and nutritional parameters in cancer patients. Therefore, plasma LPC concentrations were assessed in 59 cancer patients and related to nutritional and inflammatory parameters. To determine LPC in blood plasma we developed and validated a HPTLC method.

Results
Average plasma LPC concentration was 207 ± 59 μM which corresponds to the lower limit of the reported range in healthy subjects. No correlation between LPC and age, performance status, body mass index (BMI) or fat mass could be seen. However, LPC correlated inversely with plasma C-reactive protein (CRP) and whole blood hydrogen peroxides (HPO). Further, a negative correlation could be observed between LPC and whole body extra cellular fluid volume (ECF) as well as with relative change in body weight since cancer diagnosis.

Conclusion
In conclusion, LPC concentrations were decreased in cancer patients. LPC plasma concentrations correlated with weight loss and inflammatory parameters and, therefore, might be a general indicator of severity of malignant disease.
Relaxin family peptide receptors Rxfp1 and Rxfp2: mapping of the mRNA and protein distribution in the reproductive tract of the male rat
Authors: Filonzi Marcelo , Cardoso Laís C , Pimenta Maristela T , Queiróz Daniel BC , Avellar Maria CW , Porto Catarina S , Lazari Maria FM 
Published: July 2007

Abstract

Background
Relaxin is the endogenous ligand of the G-protein coupled receptor RXFP1, previously known as LGR7. In humans relaxin can also activate, but with lower affinity, the closely related receptor for the insulin-like peptide from Leydig cells, RXFP2, previously known as LGR8. The lack of relaxin impairs male fertility but the precise distribution and the function of relaxin receptors in the male reproductive tract is not known. We investigated the distribution of Rxfp1 and Rxfp2 in the reproductive tract of the male rat and the function of relaxin in the vas deferens, a tissue with high expression of both receptors.

Methods
The presence of mRNA for Rxfp1 and Rxfp2 was investigated in testes, cultured Sertoli cells, epididymis, vas deferens, seminal vesicle, prostate, and spermatozoa by RT-PCR and Southern blot. Protein expression in the testis, vas deferens, primary culture of Sertoli cells, and spermatozoa was assessed by immunohistochemistry and immunofluorescence. The role of relaxin in the vas deferens was evaluated by contractility studies and radioimmunoassay of cAMP production. The effect of relaxin on mRNA levels for metalloproteinase-7 was measured by Northern blot.

Results
Transcripts for Rxfp1 and Rxfp2 were present in almost all parts of the male reproductive tract, with high levels in testis and vas deferens. Both receptors were immunolocalized in late stage germ cells but not in mature spermatozoa, although mRNAs for both receptors were also present in mature spermatozoa. Rxfp1 but not Rxfp2 was detected in cultured Sertoli cells. Strong immunostaining for Rxfp1 and Rxfp2 was seen in muscular and epithelial layers of the vas deferens and in arteriolar walls. Relaxin did not affect contractility and cyclic AMP production of the vas deferens, but increased the levels of mRNA for metalloproteinase-7.

Conclusion
Rxfp1 and Rxfp2 are widely and similarly distributed throughout the male reproductive tract. Our results suggest that Rxfp1 on spermatids and Sertoli cells may be important in spermatogenesis. Relaxin in the vas deferens does not affect contractility, but may affect vascular compliance and collagen and matrix remodeling.