bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manganese‐52 positron emission tomography tracer characterization and initial results in phantoms and in vivo
Authors: Topping Geoffrey J. , Schaffer Paul , Hoehr Cornelia , Ruth Thomas J. , Sossi Vesna 
Published: March 2013

Purpose:Manganese(II) is employed as a contrast agent with magnetic resonance imaging (MRI) for study of neuronal activation in rats and mice. However, at the concentrations required for MRI, Mn may induce pharmacological or toxic effects. Positron emission tomography (PET) imaging of52MnCl2 at tracer doses has the potential to allow similar Mn studies as manganese‐enhanced MRI while providing quantitative results and avoiding toxic effects. In this work, 52MnCl2 is produced and characterized as a PET tracer in phantoms and in rats.Methods:52MnCl2 was produced by proton irradiation of natural Cr foil and separated by column chromatography. Images were acquired on a Siemens Focus 120 small animal PET scanner. Phantom images were acquired to assess uniformity, resolution, cascade background correction, and count rate linearity. Images of rats were also acquired after systemic and intracerebroventricular (ICV) administration of 52MnCl2 to investigate Mn(II) distribution in vivo.Results:Irradiation yield was 74.6 ± 8.5 kBq/μA min 52Mn at end of bombardment with initial specific activity of at least 3.5 MBq/nmol. 52Mn PET images show similar uniformity and resolution to 18F. 18F based detector efficiency normalization is adequate for 52Mn imaging. Subtraction of a rescaled random events distribution from sinogram data is effective for cascade correction of 52Mn PET data. After systemic injection, 52Mn appears in structures throughout the body of rats, including bones, liver, intestines, and the pituitary gland, but does not appear detectably throughout the brain. After ICV injection, 52Mn remains in the brain and spinal cord.Conclusions:52Mn is a promising tracer for small animal PET imaging, yielding image quality comparable to 18F. Potential applications include studies similar to Mn‐enhanced neuronal MRI, and in other organ systems including bones, spinal cord, and the digestive tract.
Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sitesa)
Authors: Zorlu Faruk , Dugel Gozde , Ozyigit Gokhan , Hurmuz Pervin , Cengiz Mustafa , Yildiz Ferah , Akyol Fadil , Gurkaynak Murat 
Published: March 2013

Purpose:The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations.Methods:The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotal skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA).Results:The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035–2.71 Gy) and 0.34 Gy (range, 0.066–3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03–0.159 Gy) and 0.05 Gy (range, 0.015–0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056–1.97 Gy) and 0.306 Gy (range, 0.065–2.25 Gy).Conclusions:Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.
Targeting Mycobacterium tuberculosis and Other Microbial Pathogens Using Improved Synthetic Antibacterial Peptides
Authors: Ramón-García Santiago , Mikut Ralf , Ng Carol , Ruden Serge , Volkmer Rudolf , Reischl Markus , Hilpert Kai , Thompson Charles J. 
Published: March 2013

ABSTRACT

The lack of effective therapies for treating tuberculosis (TB) is a global health problem. While
Mycobacterium tuberculosis
is notoriously resistant to most available antibiotics, we identified synthetic short cationic antimicrobial peptides that were active at low micromolar concentrations (less than 10 μM). These small peptides (averaging 10 amino acids) had remarkably broad spectra of antimicrobial activities against both bacterial and fungal pathogens and an indication of low cytotoxicity. In addition, their antimicrobial activities displayed various degrees of species specificity that were not related to taxonomy. For example,
Candida albicans
and
Staphylococcus aureus
were the best surrogates to predict peptide activity against
M. tuberculosis
, while
Mycobacterium smegmatis
was a poor surrogate. Principle component analysis of activity spectrum profiles identified unique features associated with activity against
M. tuberculosis
that reflect their distinctive amino acid composition; active peptides were more hydrophobic and cationic, reflecting increased tryptophan with compensating decreases in valine and other uncharged amino acids and increased lysine. These studies provide foundations for development of cationic antimicrobial peptides as potential new therapeutic agents for TB treatment.
Novel 16S rRNA Methyltransferase RmtH Produced by Klebsiella pneumoniae Associated with War-Related Trauma
Authors: O'Hara Jessica A. , McGann Patrick , Snesrud Erik C. , Clifford Robert J. , Waterman Paige E. , Lesho Emil P. , Doi Yohei 
Published: March 2013

ABSTRACT

Klebsiella pneumoniae
strain MRSN2404 was isolated from the chronic wound of a soldier who had been wounded in Iraq in 2006. The strain displayed very high MICs of all aminoglycosides, including arbekacin. A gene encoding a novel 16S rRNA methyltransferase, now designated RmtH, was identified. RmtH had 64% identity with RmtB1 and RmtB2.
rmtH
was bracketed by two copies of IS
CR2
, which may have played a role in its mobilization.
Activity of Halogeno-Thiazolides against Cryptosporidium parvum in Experimentally Infected Immunosuppressed Gerbils (Meriones unguiculatus)
Authors: Gargala Gilles , François Arnaud , Favennec Loïc , Rossignol Jean-François 
Published: March 2013

ABSTRACT

Nitazoxanide and three halogeno-thiazolides, RM-4850, RM-4865, and RM-5038, were tested against
Cryptosporidium parvum
in experimentally infected immunosuppressed Mongolian gerbils. Daily 400-mg/kg doses of the four test drugs for 5 to 8 consecutive days produced similar reductions of oocyst shedding. Using early-infected gerbils, a shorter 4-day treatment with RM-5038 reduced oocyst shedding by 95%, compared to 47% for nitazoxanide (
P
= 0.02), suggesting that RM-5038 is more effective than nitazoxanide under the experimental conditions used.
TEM-187, a New Extended-Spectrum β-Lactamase with Weak Activity in a Proteus mirabilis Clinical Strain
Authors: Corvec Stéphane , Beyrouthy Racha , Crémet Lise , Aubin Guillaume Ghislain , Robin Frédéric , Bonnet Richard , Reynaud Alain 
Published: March 2013

ABSTRACT

A
Proteus mirabilis
clinical strain (7001324) was isolated from urine sample of a patient hospitalized in a long-term-care facility. PCR and cloning experiments performed with this strain identified a novel TEM-type β-lactamase (TEM-187) differing by four amino acid substitutions (Leu21Phe, Arg164His, Ala184Val, and Thr265Met) from TEM-1. This characterization provides further evidence for the diversity of extended-spectrum β-lactamases (ESBL) produced by
P. mirabilis
and for their potential spread to other
Enterobacteriaceae
due to a lack of sensitive detection methods used in daily practice.
Early
In Vitro
and
In Vivo
Development of High-Level Daptomycin Resistance Is Common in Mitis Group Streptococci after Exposure to Daptomycin
Authors: García-de-la-Mària Cristina , Pericas Juan M. , del Río Ana , Castañeda Ximena , Vila-Farrés Xavier , Armero Yolanda , Espinal Paula A. , Cervera Carlos , Soy Dolors , Falces Carlos , Ninot Salvador , Almela Manel , Mestres Carlos A. , Gatell Jose M. , Vila Jordi , Moreno Asuncion , Marco Francesc , Miró Jose M. 
Published: March 2013

ABSTRACT

The development of high-level daptomycin resistance (HLDR; MIC of ≥256 mg/liter) after exposure to daptomycin has recently been reported in viridans group streptococcus (VGS) isolates. Our study objectives were as follows: to know whether
in vitro
development of HLDR after exposure to daptomycin was common among clinical isolates of VGS and
Streptococcus bovis
; to determine whether HLDR also developed during the administration of daptomycin to treat experimental endocarditis caused by the daptomycin-susceptible, penicillin-resistant
Streptococcus mitis
strain
S. mitis
351; and to establish whether combination with gentamicin prevented the development of HLDR
in vitro
and
in vivo. In vitro
studies were performed with 114 VGS strains (mitis group, 92; anginosus group, 10; mutans group, 8; and salivarius group, 4) and 54
Streptococcus bovis
strains isolated from 168 consecutive patients with infective endocarditis diagnosed between 1995 and 2010. HLDR was only observed after 24 h of exposure to daptomycin in 27% of the mitis group, including 27% of
S. mitis
isolates, 47% of
S. oralis
isolates, and 13% of
S. sanguis
isolates. In our experimental model, HLDR was detected in 7/11 (63%) and 8/12 (67%) isolates recovered from vegetations after 48 h of daptomycin administered at 6 mg/kg of body weight/24 h and 10 mg/kg/24 h, respectively.
In vitro
, time-kill experiments showed that daptomycin plus gentamicin was bactericidal against
S. mitis
351 at tested concentrations of 0.5 and 1 times the MIC and prevented the development of HLDR.
In vivo
, the addition of gentamicin at 1 mg/kg/8 h to both daptomycin arms prevented HLDR in 21 out of 23 (91%) rabbits. Daptomycin plus gentamicin was at least as effective as vancomycin plus gentamicin. In conclusion, HLDR develops rapidly and frequently
in vitro
and
in vivo
among mitis group streptococci. Combining daptomycin with gentamicin enhanced its activity and prevented the development of HLDR in most cases.
Activities of First-Choice Antimicrobials against Gamma Interferon-Treated Chlamydia trachomatis Differ in Hypoxia
Authors: Shima Kensuke , Klinger Matthias , Solbach Werner , Rupp Jan 
Published: March 2013

ABSTRACT

Gamma interferon (IFN-γ)-mediated host responses play a central role in resolving genital
Chlamydia trachomatis
infections but may also result in persistence of the pathogen, which shows reduced susceptibility to antimicrobials. The antichlamydial function of IFN-γ is oxygen dependent, and the efficacy of antimicrobials against
C. trachomatis
is reduced in a low-oxygen environment. In this study, we show that the antichlamydial efficacies of azithromycin and doxycycline differ in IFN-γ-treated cells under hypoxia.
Pharmacokinetic Interaction between Telaprevir and Methadone
Authors: van Heeswijk Rolf , Verboven Peter , Vandevoorde Ann , Vinck Petra , Snoeys Jan , Boogaerts Griet , De Paepe Els , Van Solingen-Ristea Rodica , Witek James , Garg Varun 
Published: March 2013

ABSTRACT

Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of
R-
and
S
-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound
R
-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (
C
min
), the maximum plasma concentration (
C
max
), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC
0–24
) for
R
-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC
0–24
ratio of
S
-methadone/
R
-methadone was not altered. The median unbound percentage of
R
-methadone increased by 26% in the presence of telaprevir. The
R
-methadone median (absolute) unbound
C
min
values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total
R
-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound
R
-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.)
Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels
Authors: Vieira Monica L. , Alvarez-Flores Miryam P. , Kirchgatter Karin , Romero Eliete C. , Alves Ivy J. , de Morais Zenaide M. , Vasconcellos Silvio A. , Chudzinski-Tavassi Ana M. , Nascimento Ana L. T. O. 
Published: March 2013

ABSTRACT

We have recently reported the ability of
Leptospira
to capture plasminogen (PLG) and generate plasmin (PLA) bound on the microbial surface in the presence of exogenous activators. In this work, we examined the effects of leptospiral PLG binding for active penetration through the endothelial cell barrier and activation. The results indicate that leptospires with PLG association or PLA activation have enhanced migration activity through human umbilical vein endothelial cell (HUVEC) monolayers compared with untreated bacteria.
Leptospira
cells coated with PLG were capable of stimulating the expression of PLG activators by HUVECs. Moreover, leptospires endowed with PLG or PLA promoted transcriptional upregulation matrix metalloprotease 9 (MMP-9). Serum samples from patients with confirmed leptospirosis showed higher levels of PLG activators and total MMP-9 than serum samples from normal (healthy) subjects. The highest level of PLG activators and total MMP-9 was detected with microscopic agglutination test (MAT)-negative serum samples, suggesting that this proteolytic activity stimulation occurs at the early stage of the disease. Furthermore, a gelatin zymography profile obtained for MMPs with serum samples from patients with leptospirosis appears to be specific to leptospiral infection because serum samples from patients with unrelated infectious diseases produced no similar degradation bands. Altogether, the data suggest that the
Leptospira
-associated PLG or PLA might represent a mechanism that contributes to bacterial penetration of endothelial cells through an activation cascade of events that enhances the proteolytic capability of the organism. To our knowledge, this is the first proteolytic activity associated with leptospiral pathogenesis described to date.
Vaccination with the Recombinant Major Outer Membrane Protein Elicits Antibodies to the Constant Domains and Induces Cross-Serovar Protection against Intranasal Challenge with Chlamydia trachomatis
Authors: Tifrea Delia F. , Ralli-Jain Pooja , Pal Sukumar , de la Maza Luis M. 
Published: March 2013

ABSTRACTTo determine the ability of the major outer membrane protein (MOMP) to elicit cross-serovar protection, groups of mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with recombinant MOMP (rMOMP) fromChlamydia trachomatisserovars D (UW-3/Cx), E (Bour), or F (IC-Cal-3) orChlamydia muridarumstrain Nigg II using CpG-1826 and Montanide ISA 720 VG as adjuvants. Negative-control groups were immunized i.m. and s.c. withNeisseria gonorrhoeaerecombinant porin B (Ng-rPorB) or i.n. with Eagle's minimal essential medium (MEM-0). Following vaccination, the mice developed antibodies not only against the homologous serovar but also against heterologous serovars. The rMOMP-vaccinated animals also mounted cell-mediated immune responses as assessed by a lymphoproliferative assay. Four weeks after the last immunization, mice were challenged i.n. with 104inclusion-forming units (IFU) ofC. muridarum. The mice were weighed for 10 days and euthanized, and the number of IFU in their lungs was determined. At 10 days postinfection (p.i.), mice immunized with the rMOMP ofC. muridarumorC. trachomatisD, E, or F had lost 4%, 6%, 8%, and 8% of their initial body weight, respectively, significantly different from the negative-control groups (Ng-rPorB, 13%; MEM-0, 19%;P< 0.05). The median number of IFU recovered from the lungs of mice immunized withC. muridarumrMOMP was 0.13 × 106. The median number of IFU recovered from mice immunized with rMOMP from serovars D, E, and F were 0.38 × 106, 7.56 × 106, and 11.94 × 106IFU, respectively. All the rMOMP-immunized animals had significantly less IFU than theNg-rPorB (40 × 106)- or MEM-0 (70 × 106)-immunized mice (P< 0.05). In conclusion, vaccination with rMOMP can elicit protection against homologous and heterologousChlamydiaserovars.
Does changing policy to disallow body checking reduce the risk of concussion in 11 and 12-year-old ice hockey players?
Authors: Emery C A , Macpherson A , Kang J , Hagel B , Black A , Romiti M , Meeuwisse W H 
Published: March 2013

ObjectiveThe objective of this study was to determine if the risk of concussion differed for non-elite Pee Wee ice hockey players (ages 11–12) in leagues where Body Checking (BC) is permitted (Alberta, Canada) versus leagues where policy no longer permits BC (Ontario, Canada).DesignCohort study.SettingCommunity ice rinks and sport medicine clinics during the 2011/12 season.ParticipantsForty-four teams from Alberta (n=658) and 32 from Ontario (n=258) participated. Players were from non-elite Pee Wee teams (lower 70% of divisions of play).Assessment of Risk FactorsNon-elite Pee Wee ice hockey leagues where BC is permitted (Alberta) compared to leagues where policy no longer permits BC (Ontario).Main Outcome MeasurementsPlayers with a suspected concussion were identified by a team therapist or safety designate and referred to a sport medicine physician.ResultsThere were 83 concussions (Incidence Proportion (IP)=12.61 (95% CI; 10.17 to 15.4)) in Alberta and 11 concussions (IP=4.26 (95% CI; 2.15 to 7.5)) in Ontario. The Concussion Risk Ratio was 2.96 (95% CI; 1.6 to 5.46). Overall, 76% of players identified with a concussion were assessed by a physician.ConclusionsThere was a 3-fold increased risk of concussion in non-elite Pee Wee ice hockey players in leagues where BC is permitted compared to a cohort where BC is no longer permitted. These findings have important implications for further BC policy change to reduce the public health burden of injury and concussion in youth ice hockey.AcknowledgementsThe University of Calgary Sport Injury Prevention Research Centre is one of the International Research Centres for Prevention of Injury and Protection of Athlete Health supported by the International Olympic Committee. We also acknowledge the support of Max Bell Foundation, Alberta Innovates Health Solutions and the Alberta Children's Hospital Institute for Child and Maternal Health (Alberta Children's Hospital Foundation).
Effectiveness of the particle repositioning maneuver for benign positional vertigo following traumatic brain injury
Authors: Ouchterlony Donna , Michalak Alicja , Topolovec-Vranic Jane , Rutka John A , Masanic Cheryl 
Published: March 2013

ObjectiveThe purpose of this pilot project was to explore the clinical presentation of benign positional vertigo (BPV) in patients with mild or moderate traumatic brain injury (TBI) and to determine if a non-invasive bedside intervention, the Particle Repositioning Maneuver (PRM) would be effective in treating BPV.DesignObservational, cohort prospective study, with repeated measures of three groups of patients diagnosed with TBI.SettingSubjects were recruited from an out-patient clinic specialising in the management of TBI in a large, urban, academic hospital.Participants56 subjects with mild to moderate TBI: 21 patients with BPV, 23 with non-specific dizziness, and 12 without any form of dizziness.InterventionPatients were assessed at baseline and at 1, 5, 9 weeks and 3 months post-enrollment. BPV was confirmed by the administration of the Dix-Hall Pike Maneuver to patients with dizziness at each assessment and those positive for BPV received PRM treatment.Outcome MeasuresDemographic and injury-related data were collected and the Dizziness Handicap Inventory (DHI) and Short-Form Health Survey (SF-36) were administered at each assessment. Mean difference in DHI scores between baseline and follow-ups were assessed.ResultsDHI scores were significantly reduced in the BPV group (20.6; p<0.01) and dizziness symptoms had resolved in 52% of patients. A significant improvement on the SF-36 physical component scores was found for the BPV group (increasing from 38.1 at baseline to 45.7 at 3 months; p<0.01)ConclusionsOur pilot study demonstrated both significantly improved dizziness symptoms and physical wellbeing for BPV patients who received PRM treatment.Competing interestsNone.
What factors increase the risk of concussion in elite youth ice hockey players?
Authors: Blake Tracy A , Kang Jian , Meeuwisse Willem H , Lemke Nicole , Schneider Kathryn J , Taylor Kirsten A , Emery Carolyn A 
Published: March 2013

ObjectiveTo examine the risk of concussion amongst elite youth male and female ice hockey players.DesignProspective cohort study.SettingCommunity ice rinks and sport medicine clinics.Participants764 Bantam (12–14 years) and Midget (15–17 years) ice hockey players. Assessment of Risk Factors: 743 players completed baseline SCAT2 testing (2011/2012 season). Age group, sex, previous concussion history, Total Symptoms Score (TSS), Balance Error Score (BES), Standardised Assessment of Concussion (SAC) Score and SCAT2 Total Score at baseline were evaluated as potential risk factors. Higher scores indicate greater impairment or symptoms.Main Outcome MeasurementsPlayers with a suspected concussion were assessed by a team therapist and referred to a sport medicine physician.ResultsMultivariate Poisson Regression analyses, adjusted for cluster by team, were used to estimate concussion risk ratios (RR). The RR for Bantam players with previous concussion history was 1.15 (95% CI 0.69 to 1.90) and for Midget players with previous concussion history was 2.83 (95% CI 1.69 to 4.72) compared to players in the same age group with no previous concussion history. The RR for players with baseline TSS and SCAT2 Total Score in the lowest 25%ile were 1.54 (95% CI 1.07 to 2.20) and 1.40 (95% CI 1.03 to 1.90), respectively, compared to those in the upper 75%ile. Sex, BES and SAC score were not predictive of concussion.ConclusionsThere is a greater risk of concussion in elite ice hockey players 15–17 years old with a previous history of concussion. Baseline TSS and SCAT2 Total Score in the lowest 25%ile are also predictive of concussion.AcknowledgementsThe University of Calgary Sport Injury Prevention Research Centre is one of the International Research Centres for Prevention of Injury and Protection of Athlete Health supported by the International Olympic Committee. We also acknowledge the support of Alberta Innovates Health Solutions, the Alberta Children's Hospital Institute for Child and Maternal Health (Alberta Children's Hospital Foundation) and Talisman Energy for their generous support.