bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiofilm and Membrane-Damaging Potential of Cuprous Oxide Nanoparticles against Staphylococcus aureus with Reduced Susceptibility to Vancomycin
Authors: Singh Avinash , Ahmed Asar , Prasad Kashi N. , Khanduja Sonali , Singh Satyendra K. , Srivastava Janmejai K. , Gajbhiye Namdeo S. 
Published: August 2015

ABSTRACT

The antimicrobial effects of copper ions and salts are well known, but the effects of cuprous oxide nanoparticles (Cu
2
O-NPs) on staphylococcal biofilms have not yet been clearly revealed. The present study evaluated Cu
2
O-NPs for their antibacterial and antibiofilm activities against heterogeneous vancomycin-intermediate
Staphylococcus aureus
(hVISA) and vancomycin-intermediate
S. aureus
(VISA). Nanoscaled Cu
2
O, generated by solution phase technology, contained Cu
2
O octahedral nanoparticles. Field emission electron microscopy demonstrated particles with sizes ranging from 100 to 150 nm. Cu
2
O-NPs inhibited the growth of
S. aureus
and showed antibiofilm activity. The MICs and minimum biofilm inhibitory concentrations ranged from 625 μg/ml to 5,000 μg/ml and from 2,500 μg/ml to 10,000 μg/ml, respectively. Exposure of
S. aureus
to Cu
2
O-NPs caused leakage of the cellular constituents and increased uptake of ethidium bromide and propidium iodide. Exposure also caused a significant reduction in the overall vancomycin-BODIPY (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3
a
,4
a
-diaza-
s
-indacene] fluorescent dye) binding and a decrease in the viable cell count in the presence of 7.5% sodium chloride. Cu
2
O-NP toxicity assessment by hemolysis assay showed no cytotoxicity at 625 to 10,000 μg/ml concentrations. The results suggest that Cu
2
O-NPs exert their action by disruption of the bacterial cell membrane and can be used as effective antistaphylococcal and antibiofilm agents in diverse medical devices.
In Vitro
Interactions of Antifungal Agents and Tacrolimus against Aspergillus Biofilms
Authors: Gao Lujuan , Sun Yi 
Published: August 2015

ABSTRACT

Aspergillus
biofilms were prepared from
Aspergillus fumigatus
,
Aspergillus flavus
, and
Aspergillus terreus
via a 96-well plate-based method, and the combined antifungal activity of tacrolimus with azoles or amphotericin B against
Aspergillus
biofilms was investigated via a broth microdilution checkerboard technique system. Our results suggest that combinations of tacrolimus with voriconazole or amphotericin B have synergistic inhibitory activity against
Aspergillus
biofilms. However, combinations of tacrolimus with itraconazole or posaconazole exhibit no synergistic or antagonistic effects.
Dissemination of Carbapenemase-Producing Enterobacteriaceae and Pseudomonas aeruginosa in Romania
Authors: Dortet Laurent , Flonta Mirela , Boudehen Yves-Marie , Creton Elodie , Bernabeu Sandrine , Vogel Anaïs , Naas Thierry 
Published: August 2015

ABSTRACT

Fifteen carbapenemase-producing
Enterobacteriaceae
isolates and 12 carbapenemase-producing
Pseudomonas aeruginosa
isolates were recovered from patients hospitalized between August 2011 and March 2013 at the Hospital of Infectious Disease, Cluj-Napoca, Romania. One KPC-, nine NDM-1-, four OXA-48-, and one VIM-4-producing
Enterobacteriaceae
isolates along with 11 VIM-2-producing and one IMP-13-producing
P. aeruginosa
isolates were recovered from clinical samples. All carbapenemase genes were located on self-conjugative plasmids and were associated with other resistance determinants, including extended-spectrum β-lactamases and RmtC methylases.
Novel Insights into the Molecular Events Linking to Cell Death Induced by Tetracycline in the Amitochondriate Protozoan Trichomonas vaginalis
Authors: Huang Kuo-Yang , Ku Fu-Man , Cheng Wei-Hung , Lee Chi-Ching , Huang Po-Jung , Chu Lichieh Julie , Cheng Chih-Chieh , Fang Yi-Kai , Wu Hsueh-Hsia , Tang Petrus 
Published: August 2015

ABSTRACT

Trichomonas vaginalis
colonizes the human urogenital tract and causes trichomoniasis, the most common nonviral sexually transmitted disease. Currently, 5-nitroimidazoles are the only recommended drugs for treating trichomoniasis. However, increased resistance of the parasite to 5-nitroimidazoles has emerged as a highly problematic public health issue. Hence, it is essential to identify alternative chemotherapeutic agents against refractory trichomoniasis. Tetracycline (TET) is a broad-spectrum antibiotic with activity against several protozoan parasites, but the mode of action of TET in parasites remains poorly understood. The
in vitro
effect of TET on the growth of
T. vaginalis
was examined, and the mode of cell death was verified by various apoptosis-related assays. Next-generation sequencing-based RNA sequencing (RNA-seq) was employed to elucidate the transcriptome of
T. vaginalis
in response to TET. We show that TET has a cytotoxic effect on both metronidazole (MTZ)-sensitive and -resistant
T. vaginalis
isolates, inducing some features resembling apoptosis. RNA-seq data reveal that TET significantly alters the transcriptome via activation of specific pathways, such as aminoacyl-tRNA synthetases and carbohydrate metabolism. Functional analyses demonstrate that TET disrupts the hydrogenosomal membrane potential and antioxidant system, which concomitantly elicits a metabolic shift toward glycolysis, suggesting that the hydrogenosomal function is impaired and triggers cell death. Collectively, we provide
in vitro
evidence that TET is a potential alternative therapeutic choice for treating MTZ-resistant
T. vaginalis
. The in-depth transcriptomic signatures in
T. vaginalis
upon TET treatment presented here will shed light on the signaling pathways linking to cell death in amitochondriate organisms.
In Vivo
Formation of the Protein Disulfide Bond That Enhances the Thermostability of Diphosphomevalonate Decarboxylase, an Intracellular Enzyme from the Hyperthermophilic Archaeon Sulfolobus solfataricus
Authors: Hattori Ai , Unno Hideaki , Goda Shuichiro , Motoyama Kento , Yoshimura Tohru , Hemmi Hisashi 
Published: August 2015

ABSTRACT

In the present study, the crystal structure of recombinant diphosphomevalonate decarboxylase from the hyperthermophilic archaeon
Sulfolobus solfataricus
was solved as the first example of an archaeal and thermophile-derived diphosphomevalonate decarboxylase. The enzyme forms a homodimer, as expected for most eukaryotic and bacterial orthologs. Interestingly, the subunits of the homodimer are connected via an intersubunit disulfide bond, which presumably formed during the purification process of the recombinant enzyme expressed in
Escherichia coli
. When mutagenesis replaced the disulfide-forming cysteine residue with serine, however, the thermostability of the enzyme was significantly lowered. In the presence of β-mercaptoethanol at a concentration where the disulfide bond was completely reduced, the wild-type enzyme was less stable to heat. Moreover, Western blot analysis combined with nonreducing SDS-PAGE of the whole cells of
S. solfataricus
proved that the disulfide bond was predominantly formed in the cells. These results suggest that the disulfide bond is required for the cytosolic enzyme to acquire further thermostability and to exert activity at the growth temperature of
S. solfataricus
.

IMPORTANCE
This study is the first report to describe the crystal structures of archaeal diphosphomevalonate decarboxylase, an enzyme involved in the classical mevalonate pathway. A stability-conferring intersubunit disulfide bond is a remarkable feature that is not found in eukaryotic and bacterial orthologs. The evidence that the disulfide bond also is formed in
S. solfataricus
cells suggests its physiological importance.
Minimal Peptidoglycan (PG) Turnover in Wild-Type and PG Hydrolase and Cell Division Mutants of Streptococcus pneumoniae D39 Growing Planktonically and in Host-Relevant Biofilms
Authors: Boersma Michael J. , Kuru Erkin , Rittichier Jonathan T. , VanNieuwenhze Michael S. , Brun Yves V. , Winkler Malcolm E. 
Published: August 2015

ABSTRACT

We determined whether there is turnover of the peptidoglycan (PG) cell wall of the ovococcus bacterial pathogen
Streptococcus pneumoniae
(pneumococcus). Pulse-chase experiments on serotype 2 strain D39 radiolabeled with
N
-acetylglucosamine revealed little turnover and release of PG breakdown products during growth compared to published reports of PG turnover in
Bacillus subtilis
. PG dynamics were visualized directly by long-pulse–chase–new-labeling experiments using two colors of
f
luorescent

d

-
a
mino
a
cid (FDAA) probes to microscopically detect regions of new PG synthesis. Consistent with minimal PG turnover, hemispherical regions of stable “old” PG persisted in D39 and TIGR4 (serotype 4) cells grown in rich brain heart infusion broth, in D39 cells grown in chemically defined medium containing glucose or galactose as the carbon source, and in D39 cells grown as biofilms on a layer of fixed human epithelial cells. In contrast,
B. subtilis
exhibited rapid sidewall PG turnover in similar FDAA-labeling experiments. High-performance liquid chromatography (HPLC) analysis of biochemically released peptides from
S. pneumoniae
PG validated that FDAAs incorporated at low levels into pentamer PG peptides and did not change the overall composition of PG peptides. PG dynamics were also visualized in mutants lacking PG hydrolases that mediate PG remodeling, cell separation, or autolysis and in cells lacking the MapZ and DivIVA division regulators. In all cases, hemispheres of stable old PG were maintained. In PG hydrolase mutants exhibiting aberrant division plane placement, FDAA labeling revealed patches of inert PG at turns and bulge points. We conclude that growing
S. pneumoniae
cells exhibit minimal PG turnover compared to the PG turnover in rod-shaped cells.

IMPORTANCE
PG cell walls are unique to eubacteria, and many bacterial species turn over and recycle their PG during growth, stress, colonization, and virulence. Consequently, PG breakdown products serve as signals for bacteria to induce antibiotic resistance and as activators of innate immune responses.
S. pneumoniae
is a commensal bacterium that colonizes the human nasopharynx and opportunistically causes serious respiratory and invasive diseases. The results presented here demonstrate a distinct demarcation between regions of old PG and regions of new PG synthesis and minimal turnover of PG in
S. pneumoniae
cells growing in culture or in host-relevant biofilms. These findings suggest that
S. pneumoniae
minimizes the release of PG breakdown products by turnover, which may contribute to evasion of the innate immune system.
Health Care Utilization, Lifestyle, and Emotional Factors and Mammography Practices in the Childhood Cancer Survivor Study
Authors: Rosenberg Shoshana M. , Moskowitz Chaya S. , Ford Jennifer S. , Henderson Tara O. , Frazier A. Lindsay , Diller Lisa R. , Hudson Melissa M. , Stanton Annette L. , Chou Joanne F. , Smith Stephanie , Leisenring Wendy M. , Mertens Ann C. , Cox Cheryl L. , Nathan Paul C. , Krull Kevin R. , Robison Leslie L. , Oeffinger Kevin C. 
Published: August 2015

AbstractBackground: Women with a history of chest radiotherapy have an increased risk of breast cancer; however, many do not undergo annual recommended screening mammography. We sought to characterize the relationship between mammography and potentially modifiable factors, with the goal of identifying targets for intervention to improve utilization.Methods: Of 625 female participants sampled from the Childhood Cancer Survivor Study, who were treated with chest radiotherapy, 551 responded to a survey about breast cancer screening practices. We used multivariate Poisson regression to assess several lifestyle and emotional factors, health care practices, and perceived breast cancer risk, in relation to reporting a screening mammogram within the last two years.Results: Women who had a Papanicolaou test [prevalence ratio (PR): 1.77; 95% confidence interval (CI) 1.26–2.49], and who perceived their breast cancer risk as higher than the average woman were more likely to have had a mammogram (PR, 1.26; 95% CI, 1.09–1.46). We detected an attenuated effect of echocardiogram screening [PR, 0.70; 95% CI (0.52–0.95)] on having a mammogram among older women compared with younger women. Smoking, obesity, physical activity, coping, and symptoms of depression and somatization were not associated with mammographic screening.Conclusion: Our findings suggest that compliance with routine and risk-based screening can be an important indicator of mammography in childhood cancer survivors. In addition, there is a need to ensure women understand their increased breast cancer risk, as a means to encouraging them to follow breast surveillance guidelines.Impact: Screening encounters could be used to promote mammography compliance in this population. Cancer Epidemiol Biomarkers Prev; 24(11); 1699–706. ©2015 AACR.
Inactivation of Endothelial Small/Intermediate Conductance of Calcium‐Activated Potassium Channels Contributes to Coronary Arteriolar Dysfunction in Diabetic Patients
Authors: Liu Yuhong , Xie An , Singh Arun K. , Ehsan Afshin , Choudhary Gaurav , Dudley Samuel , Sellke Frank W. , Feng Jun 
Published: August 2015

Background

Diabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/intermediate (

SK
C

a
/

IK
C

a
) conductance of calcium‐activated potassium channels in diabetes‐related endothelial dysfunction.

Methods and Results

Coronary arterioles (80 to 150 μm in diameter) were dissected from discarded right atrial tissues of diabetic (glycosylated hemoglobin = 9.6±0.25) and nondiabetic patients (glycosylated hemoglobin 5.4±0.12) during coronary artery bypass graft surgery (n=8/group). In‐vitro relaxation response of precontracted arterioles was examined in the presence of the selective

SK
C

a
/

IK
C

a
activator
NS
309 and other vasodilatory agents. The channel density and membrane potential of diabetic and nondiabetic endothelial cells was measured by using the whole cell patch‐clamp technique. The protein expression and distribution of the

SK
C

a
/

IK
C

a
in the human myocardium and coronary arterioles was examined by Western blotting and immunohistochemistry. Our results indicate that diabetes significantly reduced the coronary arteriolar response to the

SK
C

a
/

IK
C

a
activator
NS
309 compared to the respective responses of nondiabetic vessels (
P
<0.05 versus nondiabetes). The relaxation response of diabetic arterioles to
NS
309 was prevented by denudation of endothelium (
P
=0.001 versus endothelium‐intact). Diabetes significantly decreased endothelial

SK
C

a
/

IK
C

a
currents and hyperpolarization induced by the

SK
C

a
/

IK
C

a
activator
NS
309 as compared with that of nondiabetics. There were no significant differences in the expression and distribution of

SK
C

a
/

IK
C

a
proteins in the coronary microvessels.

Conclusions

Diabetes is associated with inactivation of endothelial

SK
C

a
/

IK
C

a
channels, which may contribute to endothelial dysfunction in diabetic patients.
Acute Heart Failure and Atrial Fibrillation: Insights From the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND‐HF) Trial
Authors: Abualnaja Seraj , Podder Mohua , Hernandez Adrian F. , McMurray John J. V. , Starling Randall C. , O'Connor Christopher M. , Califf Robert M. , Armstrong Paul W. , Ezekowitz Justin A. 
Published: August 2015

Background

Patients with acute heart failure (
AHF
) frequently have atrial fibrillation (
AF
), but how this affects patient‐reported outcomes has not been well characterized.

Methods and Results

We examined dyspnea improvement and clinical outcomes in 7007 patients in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (
ASCEND
‐
HF
) trial. At baseline, 2677 (38.2%) patients had current or a history of
AF
and 4330 (61.8%) did not. Patients with a history of
AF
were older than those without (72 vs. 63 years) and had more comorbidities and a higher median left ventricular ejection fraction (31% vs. 27%,
P
<0.001). Compared to those without
AF
, patients with
AF
had a similar mean ventricular rate on admission (81 vs. 83 beats per minute [bpm];
P
=0.138) but a lower rate at discharge (75 vs. 78 bpm;
P
<0.001). There was no difference in dyspnea improvement between patients with and without
AF
at 6 hours (
P
=0.087), but patients with
AF
had less dyspnea improvement at 24 hours (
P
<0.001). Compared to patients without
AF
, patients with
AF
had a higher 30‐day all‐cause mortality rate (4.7% vs. 3.3%;
P
=0.005), a higher 30‐day
HF
rehospitalisation rate (7.2% vs. 5.3%;
P
=0.001), and a higher coprimary composite outcome of 30‐day death or readmission (11.6% vs. 8.6%;
P
<0.001). This difference persisted after adjustment for prognostic variables (adjusted odds ratio=1.19; (95% confidence interval, 1.02 to 1.38;
P
=0.029).

Conclusions

Among patients admitted to the hospital with
AHF
, current or a history of
AF
is associated with less dyspnea improvement and higher morbidity and mortality at 30‐days, compared to those not in
AF
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00475852.
Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome
Authors: Martínez Gonzalo J. , Robertson Stacy , Barraclough Jennifer , Xia Qiong , Mallat Ziad , Bursill Christina , Celermajer David S. , Patel Sanjay 
Published: August 2015

Background

Interleukin (
IL
)‐1β,
IL
‐18, and downstream
IL
‐6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the
NLRP
3 inflammasome, a cytosolic complex responsible for the production of
IL
‐1β and
IL
‐18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (
ACS
), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production.

Methods and Results

Forty
ACS
patients, 33 with stable coronary artery disease, and 10 controls, were included.
ACS
and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for
IL
‐1β,
IL
‐18, and
IL
‐6 using
ELISA
. In
ACS
patients, coronary sinus levels of
IL
‐1β,
IL
‐18, and
IL
‐6 were significantly higher than arterial and venous levels (
P
=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus‐arterial) gradients for
IL
‐1β,
IL
‐18, and
IL
‐6 were highest in
ACS
patients and lowest in controls (
P
=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in
ACS
patients by 40% to 88% (
P
=0.028, 0.032, and 0.032, for
IL
‐1β,
IL
‐18, and
IL
‐6, respectively).

Conclusions

ACS
patients exhibit increased local cardiac production of inflammatory cytokines. Short‐term colchicine administration rapidly and significantly reduces levels of these cytokines.
Long‐Term Antiplatelet Mono‐ and Dual Therapies After Ischemic Stroke or Transient Ischemic Attack: Network Meta‐Analysis
Authors: Xie Wuxiang , Zheng Fanfan , Zhong Baoliang , Song Xiaoyu 
Published: August 2015

Background
The latest guidelines do not make clear recommendations on the selection of antiplatelet therapies for long‐term secondary prevention of stroke. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and safety of long‐term antiplatelet therapies after ischemic stroke or transient ischemic attack.

Methods and Results
We performed a network meta‐analysis of randomized controlled trials to compare 11 antiplatelet therapies in patients with ischemic stroke or transient ischemic attack. In December 2014, we searched Medline, Embase, and the Cochrane Library database for trials. The search identified 24 randomized controlled trials including a total of 85 667 patients with antiplatelet treatments for at least 1 year. Cilostazol significantly reduced stroke recurrence in comparison with aspirin (odds ratio 0.66, 95% credible interval 0.44 to 0.92) and dipyridamole (odds ratio 0.57, 95% credible interval 0.34 to 0.95), respectively. Cilostazol also significantly reduced intracranial hemorrhage compared with aspirin, clopidogrel, terutroban, ticlopidine, aspirin plus clopidogrel, and aspirin plus dipyridamole. Aspirin plus clopidogrel could not significantly reduce stroke recurrence compared with monotherapies but caused significantly more major bleeding than all monotherapies except terutroban. The pooled estimates did not change materially in the sensitivity analyses of the primary efficacy outcome.

Conclusions
Long‐term monotherapy was a better choice than long‐term dual therapy, and cilostazol had the best risk–benefit profile for long‐term secondary prevention after stroke or transient ischemic attack. More randomized controlled trials in non–East Asian patients are needed to determine whether long‐term use of cilostazol is the best option for the prevention of recurrent stroke.
Lidar and Pressure Measurements of Inner-Surfzone Waves and Setup
Authors: Brodie K. L. , Raubenheimer B. , Elgar Steve , Slocum R. K. , McNinch J. E. 
Published: August 2015

AbstractObservations of waves and setup on a steep, sandy beach are used to identify and assess potential applications of spatially dense lidar measurements for studying inner-surf and swash-zone hydrodynamics. There is good agreement between lidar- and pressure-based estimates of water levels (r2 = 0.98, rmse = 0.05 m), setup (r2 = 0.92, rmse = 0.03 m), infragravity wave heights (r2 = 0.91, rmse = 0.03 m), swell–sea wave heights (r2 = 0.87, rmse = 0.07 m), and energy density spectra. Lidar observations did not degrade with range (up to 65 m offshore of the lidar) when there was sufficient foam present on the water surface to generate returns, suggesting that for narrow-beam 1550-nm light, spatially varying spot size, grazing angle affects, and linear interpolation (to estimate the water surface over areas without returns) are not large sources of error. Consistent with prior studies, the lidar and pressure observations indicate that standing infragravity waves dominate inner-surf and swash energy at low frequencies and progressive swell–sea waves dominate at higher frequencies. The spatially dense lidar measurements enable estimates of reflection coefficients from pairs of locations at a range of spatial lags (thus spanning a wide range of frequencies or wavelengths). Reflection is high at low frequencies, increases with beach slope, and decreases with increasing offshore wave height, consistent with prior studies. Lidar data also indicate that wave asymmetry increases rapidly across the inner surf and swash. The comparisons with pressure measurements and with theory demonstrate that lidar measures inner-surf waves and setup accurately, and can be used for studies of inner-surf and swash-zone hydrodynamics.