bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of the Open Barbell and Tendo Weightlifting Analyzer Systems Versus the Optotrak Certus 3D Motion-Capture System for Barbell Velocity
Authors: Goldsmith Jacob A. , Trepeck Cameron , Halle Jessica L. , Mendez Kristin M. , Klemp Alex , Cooke Daniel M. , Haischer Michael H. , Byrnes Ryan K. , Zoeller Robert F. , Whitehurst Michael , Zourdos Michael C. 
Published: October 2018

Purpose: To examine the validity of 2 linear position transducers, the Tendo Weightlifting Analyzer System (TWAS) and Open Barbell System (OBS), compared with a criterion device, the Optotrak Certus 3-dimensional motion-capture system (OC3D). Methods: A total of 25 men (age, 25 [3] y; height, 174.0 [6.7] cm; body mass, 89.0 [14.7] kg; squat 1-repetition maximum [1RM], 175.8 [34.7] kg) with ≥2 y of resistance-training experience completed a back 1RM and 1 set to failure at 70% of 1RM. Average concentric velocity (ACV) and peak concentric velocity (PCV) were recorded by all 3 devices during the final warm-up set, all 1RM attempts, and every repetition during the 70% set. Results: In total, 575 samples were obtained. Bland–Altman plots, mountain plots, a 1-way analysis of variance, SEM, and intraclass correlation coefficients were used to analyze validity. The analysis of variance showed no difference (P = .089) between devices for ACV. However, for PCV, TWAS was significantly different (ie, inaccurate) from OC3D (P < .001) and OBS (P = .001), but OBS was similar (P = .412) to OC3D. For ACV, intraclass correlation coefficients were higher for OBS than for TWAS. Bland–Altman plots showed agreement for ACV for both devices against OC3D but large limits of agreement for PCV for both devices. Mountain plots showed valid ACV for both devices, however, but slightly greater ACV and PCV accuracy with OBS than TWAS. Conclusions: Both devices may provide valid ACV measurements, but some metrics suggest more accurate ACV with OBS vs TWAS. For PCV, neither device is particularly accurate; however, OBS seems to be more accurate than TWAS.
Recent Ankle Injury, Sport Participation Level, and Tests of Proprioception
Authors: Steinberg Nili , Adams Roger , Ayalon Moshe , Dotan Nadav , Bretter Shiri , Waddington Gordon 
Published: October 2018

Objective: Assessing the effects of ankle injury and sport participation level on ankle proprioceptive sensitivity using a joint position reproduction (JPR) test and an inversion movement extent discrimination test. Design: Cross-sectional. Setting: Biomechanics lab. Participants: Forty-five student athletes ages 21–30 (mean = 24.8 y). Main Outcome Measures: Participants were tested for ankle inversion sensitivity using 2 devices; movement reproduction error was obtained from JPR in a non-weight-bearing (N-WB) state at 10° and 15° of inversion, and an ankle proprioceptive sensitivity score was obtained from the active movement extent discrimination apparatus (AMEDA), representing the ability to differentiate 5 inversion movement extents between 10.5° and 14.5°, with testing in both N-WB and weight-bearing (WB) states. Results: For the 34 athletes with no ankle injury in the previous 12 months, the sensitivity scores achieved on the AMEDA were significantly higher (P < .01) than those for the 11 athletes with ankle injury, and the injury effect was significantly greater in WB (P = .01). In JPR testing, the 2.96° error of reproduction for athletes with no recent ankle injury was not significantly different from the 3.36° error for those with ankle injury (P = .46). Correlation of current sport participation level with JPR showed less error for higher-level performers (r = .49, P = .001) but no significant relationship to WB or N-WB AMEDA scores (both P > .61). WB AMEDA scores were significantly higher for athletes who had competed at a higher level of sport competition when <18 years old (r = −.57, P < .001). Conclusions: Previous ankle sprains affected proprioceptive scores on the WB AMEDA and N-WB AMEDA tests, indicating the sensitivity of the AMEDA movement discrimination test to the effects of ankle injury. The correlation between JPR scores and current level of sport participation suggests the sensitivity of the JPR test to current ankle use.
Mutations in Topoisomerase IV and DNA Gyrase of
Staphylococcus aureus
: Novel Pleiotropic Effects on Quinolone and Coumarin Activity
Authors: Fournier Bénédicte , Hooper David C. 
Published: October 2018

ABSTRACT

Previous studies have shown that topoisomerase IV and DNA gyrase interact with quinolones and coumarins in different ways. The MICs of coumarins (novobiocin and coumermycin) for MT5, a
Staphylococcus aureus nov
mutant, are higher than those for wild-type strains. Sequencing the
gyrB
gene encoding one subunit of the DNA gyrase revealed the presence of a double mutation likely to be responsible for this resistance: at codon 102 (Ile to Ser) and at codon 144 (Arg to Ile). For single-step
flqA
mutant MT5224c9, previously selected on ciprofloxacin, the fluoroquinolone MIC was higher and the coumarin MIC was lower than those for its parent, MT5. Sequencing the
grlB
and
grlA
genes of topoisomerase IV of MT5224c9 showed a single Asn-470-to-Asp mutation in GrlB. Genetic outcrosses by transformation with chromosomal DNA and introduction of plasmids carrying either the wild-type or the mutated
grlB
gene indicated that this mutation causes both increased MICs of fluoroquinolones and decreased MICs of coumarins and that the mutant
grlB
allele is codominant for both phenotypes with multicopy alleles. Integration of these plasmids into the chromosome confirmed the codominance of fluoroquinolone resistance, but
grlB
+
appeared dominant over
grlB
(Asp-470) for coumarin resistance. Finally, the
gyrA
(Leu-84) mutation previously described as silent for fluoroquinolone resistance increased the MIC of nalidixic acid, a nonfluorinated quinolone. Combining the
grlA
(Phe-80) and
grlB
(Asp-470) mutations with this
gyrA
mutation also had differing effects. The findings indicate that alterations in topoisomerases may have pleiotropic effects on different classes of inhibitors as well as on inhibitors within the same class. A full understanding of drug action and resistance at the molecular level must take into account both inhibitor structure-activity relationships and the effects of different classes of topoisomerase mutants.
The Lantibiotic Mersacidin Inhibits Peptidoglycan Synthesis by Targeting Lipid II
Authors: Brötz Heike , Bierbaum Gabriele , Leopold Klaus , Reynolds Peter E. , Sahl Hans-Georg 
Published: October 2018

ABSTRACT

The lantibiotic mersacidin exerts its bactericidal action by inhibition of peptidoglycan biosynthesis. It interferes with the membrane-associated transglycosylation reaction; during this step the ultimate monomeric peptidoglycan precursor, undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)-GlcNAc (lipid II) is converted into polymeric nascent peptidoglycan. In the present study we demonstrate that the molecular basis of this inhibition is the interaction of mersacidin with lipid II. The adsorption of [
14
C]mersacidin to growing cells, as well as to isolated membranes capable of in vitro peptidoglycan synthesis, was strictly dependent on the availability of lipid II, and antibiotic inhibitors of lipid II formation strongly interfered with this binding. Direct evidence for the interaction was provided by studies with isolated lipid II. [
14
C]mersacidin associated tightly with [
14
C]lipid II micelles; the complex was stable even in the presence of 1% sodium dodecyl sulfate. Furthermore, the addition of isolated lipid II to the culture broth efficiently antagonized the bactericidal activity of mersacidin. In contrast to the glycopeptide antibiotics, complex formation does not involve the C-terminal
d
-alanyl–
d
-alanine moiety of the lipid intermediate. Thus, the interaction of mersacidin with lipid II apparently occurs via a binding site which is not targeted by any antibiotic currently in use.
Comparison of the Efficacies of Three Fluoroquinolone Antimicrobial Agents, Given as Continuous or Pulsed-Water Medication, againstEscherichia coliInfection in Chickens
Authors: Charleston Bryan , Gate John J. , Aitken Ingrid A. , Stephan Bernd , Froyman Robrecht 
Published: October 2018

ABSTRACTThis study compared the efficacy of continuous or pulsed-water medication with enrofloxacin, danofloxacin, and sarafloxacin in eight groups of 90 chicks each by using an infectious bronchitis virus-Escherichia colimodel of colisepticemia. The model produced lesions of typical those occurring in birds with severe colisepticemia; for the infected, nonmedicated birds the mortality was 43.5% and the morbidity was 89%, 17.8% of birds had severe lesions, and the birds had a mean air sac lesion score of 2.58. This experiment showed that continuous dosing and pulsed dosing are clinically equivalent. However, for all fluoroquinolones studied, there was a trend for the continuously mediated birds to have lower mortality and less severe disease than birds receiving pulsed doses. Compared with infected, nonmedicated controls, only birds continuously medicated with enrofloxacin had a significantly lower morbidity (32%), and only birds medicated with enrofloxacin and danofloxacin (continuous and pulsed treatments) had significantly lower mortality (6.7 and 11.0% and 16.8 and 19.2% for continuous and pulsed treatments with enrofloxacin and danofloxacin, respectively). A significantly lower proportion of birds only in the groups medicated with enrofloxacin had severe lesions (for birds receiving continuous and pulsed treatments, 2.2 and 6.7%, respectively). Birds medicated with any of the three fluoroquinolones (continuous and pulsed treatments) except pulsed-water treatment with sarafloxacin had significantly reduced mean air sac lesion scores compared with the scores for nonmedicated birds (air sac lesion scores, 0.60 and 0.83, 1.38 and 1.63, and 1.80 and 2.05 for birds receiving continuous and pulsed treatments with enrofloxacin, danofloxacin, and sarafloxacin, respectively). The performance of the birds that survived the challenge or that recovered after receiving medication was not compromised compared to the performance of noninfected birds. Enrofloxacin was more efficacious than either danofloxacin or sarafloxacin for the treatment of colisepticemia in chickens by medication in drinking water. Similarly, danofloxacin appeared to be more effective than sarafloxacin in treating colisepticemia.
Efficacies of KY62 against
Leishmania amazonensis
and
Leishmania donovani
in Experimental Murine Cutaneous Leishmaniasis and Visceral Leishmaniasis
Authors: Al-Abdely Hail M. , Graybill John R. , Bocanegra Rosie , Najvar Laura , Montalbo Eleanor , Regen Steven L. , Melby Peter C. 
Published: October 2018

ABSTRACT

Current therapy for leishmaniasis is unsatisfactory because parenteral antimonial salts and pentamidine are associated with significant toxicity and failure rates. We examined the efficacy of KY62, a new, water-soluble, polyene antifungal, against cutaneous infection with
Leishmania amazonensis
and against visceral infection with
Leishmania donovani
in susceptible BALB/c mice. Mice were infected with
L. amazonensis
promastigotes in the ear pinna and in the tail and were treated with KY62 or amphotericin B. The cutaneous lesions showed a remarkable response to therapy with KY62 at a dose of 30 mg per kg of body weight per day. At this dose, the efficacy of KY62 was equivalent to or better than that of amphotericin B at 1 to 5 mg/kg/day. Mice infected intravenously with 10
7
L. donovani
promastigotes and treated with KY62 showed a 4-log reduction in the parasite burden in the liver and spleen compared to untreated mice. These studies indicate potent activity of KY62 against experimental cutaneous leishmaniasis caused by
L. amazoniensis
and against experimental visceral leishmaniasis caused by
L. donovani
.
Haemophilus ducreyi
Is Susceptible to Protegrin
Authors: Fortney Kate , Totten Patricia A. , Lehrer Robert I. , Spinola Stanley M. 
Published: October 2018

ABSTRACT

Protegrins, potent antimicrobial peptides found in porcine leukocytes, have activity against the sexually transmitted pathogens
Neisseria gonorrhoeae
,
Chlamydia trachomatis
, and human immunodeficiency virus type 1. We tested synthetic protegrin 1 (PG-1) for activity against nine isolates of
Haemophilus ducreyi
, the etiologic agent of chancroid. The test organisms included CIP 542 (the type strain), 35000HP (a human-passaged variant of 35000), 35000HP-RSM2 (an isogenic
d
-
glycero
-
d
-
manno
-heptosyltransferase mutant of 35000HP), and six clinical isolates. The isolates were epidemiologically unrelated, represented three
Hin
dIII ribotypes, and had varying antimicrobial resistance patterns. In bactericidal assays, five isolates were rapidly killed by synthetic PG-1. In radial diffusion assays, all nine isolates were exquisitely sensitive to PG-1. These data highlight the potential of protegrins for development as topical agents to prevent many sexually transmitted diseases, including chancroid.
Treatment of Vancomycin-Resistant
Enterococcus faecium
with RP 59500 (Quinupristin-Dalfopristin) Administered by Intermittent or Continuous Infusion, Alone or in Combination with Doxycycline, in an In Vitro Pharmacodynamic Infection Model with Simulated Endocardial Vegetations
Authors: Aeschlimann Jeffrey R. , Zervos Marcus J. , Rybak Michael J. 
Published: October 2018

ABSTRACT

Quinupristin-dalfopristin is a streptogramin antibiotic combination with activity against vancomycin-resistant
Enterococcus faecium
(VREF), but emergence of resistance has been recently reported. We studied the activity of quinupristin-dalfopristin against two clinical strains of VREF (12311 and 12366) in an in vitro pharmacodynamic model with simulated endocardial vegetations (SEVs) to determine the potential for resistance selection and possible strategies for prevention. Baseline MICs/minimal bactericidal concentrations (μg/ml) for quinupristin-dalfopristin, quinupristin, dalfopristin, and doxycycline were 0.25/2, 64/>512, 4/512, and 0.125/8 for VREF 12311 and 0.25/32, 128/>512, 2/128, and 0.25/16 for VREF 12366, respectively. Quinupristin-dalfopristin regimens had significantly less activity against VREF 12366 than VREF 12311. An 8-μg/ml simulated continuous infusion was the only bactericidal regimen with time to 99.9% killing = 90 hours. The combination of quinupristin-dalfopristin every 8 h with doxycycline resulted in more killing compared to either drug alone. Quinupristin-dalfopristin-resistant mutants (MICs, 4 μg/ml; resistance proportion, ∼4 × 10
−4
) emerged during the quinupristin-dalfopristin monotherapies for both VREF strains. Resistance was unstable in VREF 12311 and stable in VREF 12366. The 8-μg/ml continuous infusion or addition of doxycycline to quinupristin-dalfopristin prevented the emergence of resistance for both strains over the 96-h test period. These findings replicated the development of resistance reported in humans and emphasized bacterial factors (drug susceptibility, high inoculum, organism growth phase) and infectious conditions (penetration barriers) which could increase chances for clinical resistance. The combination of quinupristin-dalfopristin with doxycycline and the administration of quinupristin-dalfopristin as a high-dose continuous infusion warrant further study to determine their potential clinical utility.
In Vitro Activity of the Echinocandin Antifungal Agent LY303,366 in Comparison with Itraconazole and Amphotericin B against
Aspergillus
spp
Authors: Oakley Karen L. , Moore Caroline B. , Denning David W. 
Published: October 2018

ABSTRACT

LY303,366 (LY) is a novel derivative of the echinocandin class of antifungal agents. The in vitro activities of LY, itraconazole (ITZ), and amphotericin B (AMB) were assessed against 60
Aspergillus
isolates, including 35 isolates of
A. fumigatus
, eight isolates of
A. terreus
, eight isolates of
A. flavus
, eight isolates of
A. niger
and one isolate of
A. nidulans
. Four
A. fumigatus
isolates were resistant to ITZ. Susceptibility testing for all drugs was performed with a broth microdilution procedure. LY was tested in two media: antibiotic medium 3 (AM3) and Casitone with 2% glucose (CAS) with an inoculum of 2 × 10
3
spores/ml. ITZ and AMB were tested in RPMI 1640 with 2% glucose with an inoculum of 1 × 10
6
spores/ml. All tests were incubated at 37°C for 48 h. A novel end point was used to determine a minimal effective concentration (MEC) for LY, i.e., almost complete inhibition of growth save a few tiny spherical colonies attached to the microplate. MICs were measured for ITZ and AMB with a no-growth end point. Ranges and geometric mean (GM) MECs were from 0.0018 to >0.5 and 0.0039 mg/liter and from 0.0018 to >0.5 and 0.008 mg/liter for LY in AM3 and LY in CAS, respectively. Differences between species were apparent, with
A. flavus
being significantly less susceptible to LY than any other species tested with both media (
P
≤ 0.05). Ranges and GM MICs were from 0.125 to >16 and 0.7 mg/liter for ITZ and from 0.25 to 16 and 1.78 mg/liter for AMB. Minimal fungicidal concentrations (MFCs) were also determined for all drugs. GM MFCs were 0.018, 0.09, 19.76, and 12.64 mg/liter for LY in AM3, LY in CAS, ITZ, and AMB, respectively. LY in AM3 and LY in CAS were fungicidal for 86.7 and 68% of isolates, respectively (98% killing). In comparison, ITZ and AMB were fungicidal for 35 and 70% of isolates, respectively (99.99% killing). A reproducibility study was performed on 20% of the isolates. For 12 isolates retested, the MEC or MIC was the same or was within 1 dilution of the original value for 11, 11, 10, and 9 isolates for LY in AM3, LY in CAS, ITZ, and AMB, respectively. In conclusion, LY seems to be a promising antifungal agent with excellent in vitro activity against
Aspergillus
spp.
Explaining the Bias in the 23S rRNA Gene Mutations Associated with Clarithromycin Resistance in Clinical Isolates of
Helicobacter pylori
Authors: Debets-Ossenkopp Y. J. , Brinkman A. B. , Kuipers E. J. , Vandenbroucke-Grauls C. M. J. E. , Kusters J. G. 
Published: October 2018

ABSTRACT

A single point mutation in the 23S rRNA gene of
Helicobacter pylori
is known to confer resistance to clarithromycin. Most prevalent among clarithromycin-resistant clinical
H. pylori
isolates are the mutations from A-2142 to G and A-2143 to G in the 23S rRNA gene. The bias in the 23S rRNA gene mutations conferring clarithromycin resistance may result from the higher MIC, stability of resistance, and growth rate found for the strains with the above-mentioned mutations.
Nitazoxanide, a Potential Drug for Eradication of
Helicobacter pylori
with No Cross-Resistance to Metronidazole
Authors: Mégraud Francis , Occhialini Alessandra , Rossignol Jean François 
Published: October 2018

ABSTRACT

Nitazoxanide, a thiazolide compound, and its desacetyl derivative, tizoxanide, have antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. Because the treatment of
Helicobacter pylori
infection may be jeopardized by metronidazole resistance, nitazoxanide and tizoxanide were tested in vitro against these bacteria. The MICs of these two compounds were determined by agar dilution and were compared to those of metronidazole. Exposure to subinhibitory concentrations of nitazoxanide was also carried out by the method of Szybalski (W. Szybalski and V. Bryson, J. Bacteriol. 64:489–499, 1952). The MICs of nitazoxanide and tizoxanide for 103 strains ranged from 0.25 to 8 μg/ml, with the MIC at which 50% of strains are inhibited (MIC
50
) being 1 μg/ml and the MIC
90
being 4 μg/ml, and no resistant strain was detected, whereas strains resistant to metronidazole were detected. When 10 strains were successively subcultured on medium containing nitazoxanide, no significant change in the MICs of this compound was observed. A pilot study of nitazoxanide for the treatment of
H. pylori
infection was carried out with 86 patients in association with 20 mg of omeprazole. An eradication rate of 83% (95% confidence interval, 64% to 94%) was obtained in a per-protocol analysis in the group receiving 1 g of nitazoxanide orally twice daily, and a few side effects were observed. The failures could not be explained by the selection of resistant strains since the MICs of nitazoxanide were similar for six pairs of isolates (proven to be the same strain by random amplified polymorphic DNA analysis in four cases) cultured before and after the treatment failure. Nitazoxanide exhibits good antimicrobial activity against
H. pylori
without the problem of acquired resistance which is encountered with metronidazole and has been demonstrated to have a satisfactory effect in a dose-ranging pilot study. It is therefore a good candidate to be included in treatment regimens aimed at the eradication of
H. pylori
.
Comparative Efficacy Evaluation of Dicationic Carbazole Compounds, Nitazoxanide, and Paromomycin against
Cryptosporidium parvum
Infections in a Neonatal Mouse Model
Authors: Blagburn Byron L. , Drain Kathryn L. , Land Tracey M. , Kinard Rachel G. , Moore P. Hutton , Lindsay David S. , Patrick Donald A. , Boykin David W. , Tidwell Richard R. 
Published: October 2018

ABSTRACT

The efficacies of dicationic carbazole compounds, nitazoxanide (NTZ), and paromomycin were evaluated against the AUCp1 isolate of
Cryptosporidium parvum
by using a neonatal mouse model. Compounds were solubilized or suspended in deionized water and administered orally by gavage to neonatal mice at a constant dose rate on days 0 to 5 (treatment started on day 0). Dose rates varied for individual carbazole compounds but ranged from 0.65 to 20 mg/kg of body weight. NTZ was tested at 100 and 150 mg/kg, and paromomycin was tested at 50 mg/kg. Efficacies were determined by comparing numbers of oocysts present in treated versus control mice at necropsy examination on day 6. Demonstrable efficacy was observed for several carbazole compounds, based on significant reductions in the numbers of oocysts recovered from treated mice versus control mice. Compounds 1, 7, and 10 (19.0 mg/kg) reduced oocyst passage in treated mice to less than 5% of that in control mice. Treatment with compounds 6, 8, and 9 (17.0 mg/kg) resulted in reductions of oocyst output to less than 10% of that in controls. Although they were not comparable in efficacy to compounds 1, 6, 7, 8, 9, and 10, treatment with other carbazole compounds resulted in statistically significant reductions in oocyst output in treated versus control mice. Compound 1 retained efficacy resulted in reduction of oocyst output to approximately 6% of that in controls when the dose was reduced to 5 mg/kg. Further reductions in the dose rate resulted in considerable reductions in anticryposporidial activity. Likewise, the efficacies of compounds 9 and 10 were reduced substantially when the doses were lowered to one-half the screening dose. Paromomycin yielded excellent activity (reduction of oocyst output to <2% of that in controls) at a dose of 50 mg/kg. NTZ yielded moderate efficacy as powder and injectable formulations administered at 100 mg/kg orally (reduction of oocyst output to 42 and 26% of that in controls, respectively). Oral administration of the injectable formulation of NTZ at a dose of 150 mg/kg resulted in improved efficacy (oocyst output, <5% of that in controls).