bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retracted: Mathematical relationships and their consequences between rat pulse waveform parameters and blood pressure during decreasing NO bioavailability
Authors: Misak Anton , Kristek Frantisek , Tomasova Lenka , Grman Marian , Ondriasova Elena , Krizanova Olga , Ondrias Karol 
Published: November 2016

New Findings
What is the central question of this study?
We wanted to find out whether the relationship between rat arterial pulse waveform (APW) parameters and blood pressure could be described by known mathematical functions and find mathematical parameters for conditions of hypertension resulting from decreased NO bioavailability.

What is the main finding and its importance?
We found mathematical functions and their parameters that approximate the relationships of 12 APW parameters to systolic and diastolic blood pressure in conditions of decreased NO bioavailability. The results may assign APW parameters to decreased NO bioavailability, which may have predictive or diagnostic value.

Information obtained from the arterial pulse waveform (APW) is useful for characterization of the cardiovascular system in particular (patho)physiological conditions. Our goal was to find out whether the relationships between rat APW parameters could be described by simple mathematical functions and to find mathematical parameters for conditions of hypertension resulting from decreased NO bioavailability. Therefore, we explored details of 14 left carotid APW parameters of anaesthetized male Wistar rats and mathematically characterized their relationship to systolic and diastolic blood pressure (BP) in conditions of a gradual reduction in NO bioavailability after administration of l‐NAME. The right jugular vein of anaesthetized Wistar rats was cannulated for l‐NAME administration. The left carotid artery was cannulated to detect the APW at high resolution. Here, we show the time‐dependent parallel changes of 14 APW parameters before and after i.v. administration of l‐NAME and present mathematical functions that approximate the relationships of 12 APW parameters to systolic and diastolic BP. Some APW parameters had minor (e.g. heart rate) or biphasic dependence on BP (e.g. relative level of the maximum rate of ventricular pressure decrease (dP/dtmin)), but all relationships, within a particular range of BP, could be approximated by known regression functions, as a linear function (e.g. pulse BP), exponential decay (e.g. relative level of the maximum rate of ventricular pressure increase (dP/dtmax)), exponential growth (systolic area), exponential rise to a maximum (relative augmentation index) or sigmoid function (e.g. increase of relative level of dP/dtmin). The mathematical functions may assign APW parameters to decreased NO bioavailability. This may have predictive or diagnostic value.
Strategies for CT tissue segmentation for Monte Carlo calculations in nuclear medicine dosimetry
Authors: Braad P. E. N. , Andersen T. , Hansen S. B. , Høilund‐Carlsen P. F. 
Published: November 2016

Purpose:CT images are used for patient specific Monte Carlo treatment planning in radionuclide therapy. The authors investigated the impact of tissue classification, CT image segmentation, and CT errors on Monte Carlo calculated absorbed dose estimates in nuclear medicine.Methods:CT errors as a function of patient size, CT reconstruction, and tube current modulation methods were assessed in a phantom experiment on a clinical CT system. The impact of tissue segmentation methods and CT number variations on EGSnrc Monte Carlo calculated absorbed dose distributions was assessed for 99mTc and 131I in the ICRP/ICRU male phantom and in a patient PET/CT‐scanned with 124I prior to radioiodine therapy.Results:CT number variations <20 HU were obtained for whole‐body CT examinations at effective CT doses ∼2 mSv. Monte Carlo calculated absorbed doses depended on both the number of media types and accurate calibration of the CT number‐to‐density conversion ramp. Tissue segmentation by a 13‐tissue CT conversion ramp, calibrated by a stoichiometric method, resulted in low (<4%) dose errors in selected organs for both isotopes.Conclusions:A calibrated CT scanner specific conversion ramp is required for accurate patient specific dosimetry in nuclear medicine. Accurate dosimetry was obtained with a 13‐tissue ramp that included five different bone types.
An efficient method to determine double Gaussian fluence parameters in the eclipse™ proton pencil beam model
Authors: Shen Jiajian , Liu Wei , Stoker Joshua , Ding Xiaoning , Anand Aman , Hu Yanle , Herman Michael G. , Bues Martin 
Published: November 2016

Purpose:To find an efficient method to configure the proton fluence for a commercial proton pencil beam scanning (PBS) treatment planning system (TPS).Methods:An in‐water dose kernel was developed to mimic the dose kernel of the pencil beam convolution superposition algorithm, which is part of the commercial proton beam therapy planning software, eclipse™ (Varian Medical Systems, Palo Alto, CA). The field size factor (FSF) was calculated based on the spot profile reconstructed by the in‐house dose kernel. The workflow of using FSFs to find the desirable proton fluence is presented. The in‐house derived spot profile and FSF were validated by a direct comparison with those calculated by the eclipse TPS. The validation included 420 comparisons of the FSFs from 14 proton energies, various field sizes from 2 to 20 cm and various depths from 20% to 80% of proton range.Results:The relative in‐water lateral profiles between the in‐house calculation and the eclipse TPS agree very well even at the level of 10−4. The FSFs between the in‐house calculation and the eclipse TPS also agree well. The maximum deviation is within 0.5%, and the standard deviation is less than 0.1%.Conclusions:The authors’ method significantly reduced the time to find the desirable proton fluences of the clinical energies. The method is extensively validated and can be applied to any proton centers using PBS and the eclipse TPS.
The Loop 2 Region of Ribosomal Protein uS5 Influences Spectinomycin Sensitivity, Translational Fidelity, and Ribosome Biogenesis
Authors: Kamath Divya , Gregory Steven T. , O'Connor Michael 
Published: November 2016

ABSTRACT

Ribosomal protein uS5 is an essential component of the small ribosomal subunit that is involved in subunit assembly, maintenance of translational fidelity, and the ribosome's response to the antibiotic spectinomycin. While many of the characterized uS5 mutations that affect decoding map to its interface with uS4, more recent work has shown that residues distant from the uS4-uS5 interface can also affect the decoding process. We targeted one such interface-remote area, the loop 2 region (residues 20 to 31), for mutagenesis in
Escherichia. coli
and generated 21 unique mutants. A majority of the loop 2 alterations confer resistance to spectinomycin and affect the fidelity of translation. However, only a minority show altered rRNA processing or ribosome biogenesis defects.
Echinocandin Resistance in Candida Species Isolates from Liver Transplant Recipients
Authors: Prigent Gwénolé , Aït-Ammar Nawel , Levesque Eric , Fekkar Arnaud , Costa Jean-Marc , El Anbassi Sarra , Foulet Françoise , Duvoux Christophe , Merle Jean-Claude , Dannaoui Eric , Botterel Françoise 
Published: November 2016

ABSTRACT

Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in
Candida
spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of
Candida
isolates to echinocandins were tested by Etest and the EUCAST reference method. Isolates were analyzed by
FKS
sequencing and genotyped based on microsatellites or multilocus sequence typing (MLST) profiles. Ninety-four patients were included, and 39 patients were colonized or infected and treated with echinocandin. Echinocandin resistance appeared in 3 (8%) of the treated patients within 1 month of treatment. One patient was colonized by resistant
Candida glabrata
, one by resistant
Candida dubliniensis
, and one by resistant
Candida albicans
. Molecular analysis found three mutations in
FKS2
HS1 (F659S, S663A, and D666E) for
C. glabrata
and one mutation in
FKS1
HS1 (S645P) for
C. dubliniensis
and
C. albicans
. Susceptible and resistant isolates belonged to the same genotype. To our knowledge, this is the first study on echinocandin resistance in
Candida
spp. in a liver transplant population. Most resistant isolates were found around/in digestive sites, perhaps due to lower diffusion of echinocandin in these sites. This work documents the risk of emergence of resistance to echinocandin, even after short-term treatment.
High Prevalence of Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations in Patients with a First Episode of Pneumocystis Pneumonia in Santiago, Chile, and Clinical Response to Trimethoprim-Sulfamethoxazole Therapy
Authors: Ponce Carolina A. , Chabé Magali , George Claudio , Cárdenas Alejandra , Durán Luisa , Guerrero Julia , Bustamante Rebeca , Matos Olga , Huang Laurence , Miller Robert F. , Vargas Sergio L. 
Published: November 2016

ABSTRACT

Mutations in the dihydropteroate synthase (DHPS) gene of
Pneumocystis jirovecii
are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for
Pneumocystis
pneumonia (PCP). The prevalence of
Pneumocystis
DHPS mutations was examined in
Pneumocystis
isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.
Emergence of Colistin Resistance Gene
mcr-1
in Cronobacter sakazakii Producing NDM-9 and in Escherichia coli from the Same Animal
Authors: Liu Bao-Tao , Song Feng-Jing , Zou Ming , Hao Zhi-Hui , Shan Hu 
Published: November 2016

ABSTRACT

We report the presence of
mcr-1
in
Escherichia coli
and carbapenem-resistant
Cronobacter sakazakii
from the same diseased chicken. The
mcr-1
gene linked with IS
Apl1
was located on two different IncI2 plasmids, including one multidrug plasmid in
E. coli
, whereas
fosA3-bla
NDM-9
was on an IncB/O plasmid in
C. sakazakii
. The development of the
fosA3-bla
NDM-9
resistance region was mediated by IS
26
. The colocation of
mcr-1
or
bla
NDM-9
with other resistance genes will accelerate the dissemination of the two genes.
Chromosomal Amplification of the
bla
OXA-58
Carbapenemase Gene in a Proteus mirabilis Clinical Isolate
Authors: Girlich Delphine , Bonnin Rémy A. , Bogaerts Pierre , De Laveleye Morgane , Huang Daniel T. , Dortet Laurent , Glaser Philippe , Glupczynski Youri , Naas Thierry 
Published: November 2016

ABSTRACT

Horizontal gene transfer may occur between distantly related bacteria, thus leading to genetic plasticity and in some cases to acquisition of novel resistance traits
. Proteus mirabilis
is an enterobacterial species responsible for human infections that may express various acquired β-lactam resistance genes, including different classes of carbapenemase genes. Here we report a
Proteus mirabilis
clinical isolate (strain 1091) displaying resistance to penicillin, including temocillin, together with reduced susceptibility to carbapenems and susceptibility to expanded-spectrum cephalosporins. Using biochemical tests, significant carbapenem hydrolysis was detected in
P. mirabilis
1091. Since PCR failed to detect acquired carbapenemase genes commonly found in
Enterobacteriaceae
, we used a whole-genome sequencing approach that revealed the presence of
bla
OXA-58
class D carbapenemase gene, so far identified only in
Acinetobacter
species. This gene was located on a 3.1-kb element coharboring a
bla
AmpC
-like gene. Remarkably, these two genes were bracketed by putative XerC-XerD binding sites and inserted at a XerC-XerD site located between the terminase-like small- and large-subunit genes of a bacteriophage. Increased expression of the two
bla
genes resulted from a 6-time tandem amplification of the element as revealed by Southern blotting. This is the first isolation of a clinical
P. mirabilis
strain producing OXA-58, a class D carbapenemase, and the first description of a XerC-XerD-dependent insertion of antibiotic resistance genes within a bacteriophage. This study revealed a new role for the XerC-XerD recombinase in bacteriophage biology.
Pharmacokinetics of the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection
Authors: Antwi Sampson , Yang Hongmei , Enimil Anthony , Sarfo Anima M. , Gillani Fizza S. , Ansong Daniel , Dompreh Albert , Orstin Antoinette , Opoku Theresa , Bosomtwe Dennis , Wiesner Lubbe , Norman Jennifer , Peloquin Charles A. , Kwara Awewura 
Published: November 2016

ABSTRACT

Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC
0–8
), maximum concentration (
C
max
), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age
Z
scores (
P
< 0.05). Rifampin, pyrazinamide, and ethambutol median body weight-normalized CL/F values were significantly higher, whereas the plasma AUC
0–8
values were lower, in the coinfected children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC
0–8
for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)
β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity
Authors: Hasim Sahar , Allison David P. , Retterer Scott T. , Hopke Alex , Wheeler Robert T. , Doktycz Mitchel J. , Reynolds Todd B. 
Published: November 2016

ABSTRACT

Candida albicans
is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of
C. albicans
is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of
C. albicans
by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the
cho1
Δ/Δ and
kre5
Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the
cho1
Δ/Δ and
kre5
Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the
kre5
Δ/Δ mutant, decreased for the
cho1
Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.
NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice
Authors: Bast Antje , Kubis Helen , Holtfreter Birte , Ribback Silvia , Martin Heiner , Schreiner Helen C. , Dominik Malte J. , Breitbach Katrin , Dombrowski Frank , Kocher Thomas , Steinmetz Ivo 
Published: November 2016

ABSTRACT

Aggregatibacter actinomycetemcomitans
is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal
A. actinomycetemcomitans
infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of
A. actinomycetemcomitans
-induced periodontitis. NADPH oxidase-deficient (gp91
phox
knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with
A. actinomycetemcomitans
and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection,
A. actinomycetemcomitans
persisted at significantly higher levels in the murine oral cavities of infected gp91
phox
KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91
phox
KO mice. Only infected gp91
phox
KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control
A. actinomycetemcomitans
infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.
Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus
Authors: Chan Liana C. , Chaili Siyang , Filler Scott G. , Miller Lloyd S. , Solis Norma V. , Wang Huiyuan , Johnson Colin W. , Lee Hong K. , Diaz Luis F. , Yeaman Michael R. 
Published: November 2016

ABSTRACTStaphylococcus aureusis the leading cause of skin and skin structure infections (SSSI). The high frequency of recurring SSSI due toS. aureus, including methicillin-resistantS. aureus(MRSA) strains, despite high titers of specific antibodies and circulating T cells, implies that traditional adaptive immunity imparts incomplete protection. We hypothesized that innate immune memory contributes to the protective host defense against recurring MRSA infection. To test this hypothesis, SSSI was induced in wild-type andrag1−/−mice in the BALB/c and C57BL/6 backgrounds. Prior infection (priming) of wild-type andrag1−/−mice of either background afforded protection against repeat infection, as evidenced by reduced abscess severities and decreased CFU densities compared to those in naive controls. Interestingly, protection was greater on the previously infected flank than on the naive flank for wild-type andrag1−/−mice. For wild-type mice, protective efficacy corresponded to increased infiltration of neutrophils (polymorphonuclear leukocytes [PMN]), macrophages (MΦ), Langerin+dendritic cells (LDC), and natural killer (NK) cells. Protection was associated with the induction of interleukin-17A (IL-17A), IL-22, and gamma interferon (IFN-γ) as well as the antimicrobial peptides CRAMP and mβD-3. Priming also protectedrag1−/−mice against recurring SSSI, with increased MΦ and LDC infiltration and induction of IL-22, CRAMP, and mβD-3. These findings suggest that innate immune memory, mediated by specific cellular and molecular programs, likely contributes to the localized host defense in recurrent MRSA SSSI. These insights support the development of targeted immunotherapeutic strategies to address the challenge of MRSA infection.