bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Antibacterial Coating on Orthopedic Wires To Eliminate Pin Tract Infections
Authors: Gil Dmitry , Shuvaev Sergey , Frank-Kamenetskii Anastasia , Reukov Vladimir , Gross Christopher , Vertegel Alexey 
Published: May 2017

ABSTRACT

Novel approaches to the prevention of microbial infections after the insertion of orthopedic external fixators are in great demand because of the extremely high incidence rates of such infections, which can reach up to 100% with longer implant residence times. Monolaurin is an antimicrobial agent with a known safety record that is broadly used in the food and cosmetic industries; however, its use in antimicrobial coatings of medical devices has not been studied in much detail. Here, we report the use of monolaurin as an antibacterial coating on external fixators for the first time. Monolaurin-coated Kirschner wires (K-wires) showed excellent antibacterial properties against three different bacterial strains, i.e., methicillin-sensitive
Staphylococcus aureus
(MSSA), methicillin-resistant
Staphylococcus aureus
(MRSA), and
Staphylococcus epidermidis
. Approximately 6.0-log reductions of both planktonic and adherent bacteria were achieved using monolaurin-coated K-wires, but monolaurin-coated K-wires did not show any observable cytotoxicity with mouse osteoblast cell cultures. Overall, monolaurin-coated K-wires could be promising as potent antimicrobial materials for orthopedic surgery.
Gepotidacin (GSK2140944)
In Vitro
Activity against Gram-Positive and Gram-Negative Bacteria
Authors: Flamm R. K. , Farrell D. J. , Rhomberg P. R. , Scangarella-Oman N. E. , Sader H. S. 
Published: May 2017

ABSTRACT

Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has
in vitro
activity against susceptible and drug-resistant pathogens. Reference
in vitro
methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for
Staphylococcus aureus
,
Streptococcus pneumoniae
, and
Escherichia coli
. Gepotidacin
in vitro
activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC
90
of gepotidacin for 50
S. aureus
(including methicillin-resistant
S. aureus
[MRSA]) and 50
S. pneumoniae
(including penicillin-nonsusceptible) isolates was 0.5 μg/ml, and for
E. coli
(
n
= 25 isolates), it was 4 μg/ml. Gepotidacin was bactericidal against
S. aureus
,
S. pneumoniae
, and
E. coli
, with MBC/MIC ratios of ≤4 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4× or 10× MIC at 24 h for all of the isolates.
S. aureus
regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to ≤4; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against
S. aureus
(≤0.6 h against MRSA and MSSA), and the PAE–sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5× MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5× MIC. These
in vitro
data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens.
Five-Year Summary of
In Vitro
Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)
Authors: Pfaller Michael A. , Mendes Rodrigo E. , Streit Jennifer M. , Hogan Patricia A. , Flamm Robert K. 
Published: May 2017

ABSTRACT

This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid
in vitro
activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against
Staphylococcus aureus
, inhibiting >99.9% of 3,031 isolates at ≤2 µg/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of
Streptococcus pneumoniae
, virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest <1% from 2011 to 2015. Staphylococci, especially
Staphylococcus epidermidis
, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of
cfr
among
Staphylococcus aureus
isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 µg/ml) to linezolid carried this transferrable gene (2011 to 2015). The
cfr
gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than
S. aureus
from 2011 to 2015. The
optrA
gene was noted in half (2/4) of the population of linezolid-nonsusceptible
Enterococcus faecalis
isolates from 2011 to 2015, while linezolid-nonsusceptible
Enterococcus faecium
isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms.
Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa
Authors: Zheng Zhaojun , Tharmalingam Nagendran , Liu Qingzhong , Jayamani Elamparithi , Kim Wooseong , Fuchs Beth Burgwyn , Zhang Rijun , Vilcinskas Andreas , Mylonakis Eleftherios 
Published: May 2017

ABSTRACT

The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrug-resistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36-residue α-helical cationic peptide derived from
Aedes aegypti
cecropin A, focusing on the common pathogen
Pseudomonas aeruginosa
. The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical
P. aeruginosa
isolates were 32 to 64 μg/ml, and its MICs versus other Gram-negative bacteria were 2 to 32 μg/ml. Importantly, cecropin A2 demonstrated synergistic activity against
P. aeruginosa
when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective
in vivo
in the
P. aeruginosa/Galleria mellonella
model (
P
< 0.001). We found that cecropin A2 bound to
P. aeruginosa
lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against
P. aeruginosa
in vitro
and
in vivo
, offering an alternative approach for the treatment of
P. aeruginosa
infections.
Novel Translation Initiation Regulation Mechanism in Escherichia coli ptrB Mediated by a 5′-Terminal AUG
Authors: Beck Heather J. , Janssen Gary R. 
Published: May 2017

ABSTRACT

Alternative translation initiation mechanisms, distinct from the Shine-Dalgarno (SD) sequence-dependent mechanism, are more prevalent in bacteria than once anticipated. Translation of
Escherichia coli
ptrB
instead requires an AUG triplet at the 5′ terminus of its mRNA. The 5′-terminal AUG (5′-uAUG) acts as a ribosomal recognition signal to attract ribosomes to the
ptrB
mRNA rather than functioning as an initiation codon to support translation of an upstream open reading frame.
ptrB
expression exhibits a stronger dependence on the 5′-uAUG than the predicted SD sequence; however, strengthening the predicted
ptrB
SD sequence relieves the necessity for the 5′-uAUG. Additional sequences within the
ptrB
5′ untranslated region (5′-UTR) work cumulatively with the 5′-uAUG to control expression of the downstream
ptrB
coding sequence (CDS), thereby compensating for the weak SD sequence. Replacement of 5′-UTRs from other mRNAs with the
ptrB
5′-UTR sequence showed a similar dependence on the 5′-uAUG for CDS expression, suggesting that the regulatory features contained within the
ptrB
5′-UTR are sufficient to control the expression of other
E. coli
CDSs. Demonstration that the 5′-uAUG present on the
ptrB
leader mRNA is involved in ribosome binding and expression of the downstream
ptrB
CDS revealed a novel form of translational regulation. Due to the abundance of AUG triplets at the 5′ termini of
E. coli
mRNAs and the ability of
ptrB
5′-UTR regulation to function independently of gene context, the regulatory effects of 5′-uAUGs on downstream CDSs may be widespread throughout the
E. coli
genome.

IMPORTANCE
As the field of synthetic biology continues to grow, a complete understanding of basic biological principles will be necessary. The increasing complexity of the synthetic systems highlights the gaps in our current knowledge of RNA regulation. This study demonstrates that there are novel ways to regulate canonical Shine-Dalgarno-led mRNAs in
Escherichia coli
, illustrating that our understanding of the fundamental processes of translation and RNA regulation is still incomplete. Even for
E. coli
, one of the most-studied model organisms, genes with translation initiation mechanisms that do not fit the canonical Shine-Dalgarno sequence paradigm are being revealed. Uncovering diverse mechanisms that control translational expression will allow synthetic biologists to finely tune protein production of desired gene products.
The Long Hunt for
pssR
—Looking for a Phospholipid Synthesis Transcriptional Regulator, Finding the Ribosome
Authors: Bartoli J. , My L. , Belmudes Lucid , Couté Yohann , Viala J. P. , Bouveret E. 
Published: May 2017

ABSTRACT

The phospholipid (PL) composition of bacterial membranes varies as a function of growth rate and in response to changes in the environment. While growth adaptation can be explained by biochemical feedback in the PL synthesis pathway, recent transcriptome studies have revealed that the expression of PL synthesis genes can also be tuned in response to various stresses. We previously showed that the BasRS two-component pathway controls the expression of the diacylglycerol kinase gene,
dgkA
, in
Escherichia coli
(A. Wahl, L. My, R. Dumoulin, J. N. Sturgis, and E. Bouveret, Mol Microbiol, 80:1260–1275, 2011,
https://doi.org/10.1111/j.1365-2958.2011.07641.x
). In this study, we set up a strategy to identify the mutation responsible for the upregulation of
pssA
observed in the historical
pssR1
mutant and supposedly corresponding to a transcriptional repressor (C. P. Sparrow and J. Raetz, J Biol Chem, 258:9963–9967, 1983).
pssA
encodes phosphatidylserine synthase, the first step of phosphatidylethanolamine synthesis. We showed that this mutation corresponded to a single nucleotide change in the anti-Shine-Dalgarno sequence of the 16S rRNA encoded by the
rrnC
operon. We further demonstrated that this mutation enhanced the translation of
pssA
. Though this effect appeared to be restricted to PssA among phospholipid synthesis enzymes, it was not specific, as evidenced by a global effect on the production of unrelated proteins.

IMPORTANCE
Bacteria adjust the phospholipid composition of their membranes to the changing environment. In addition to enzymatic regulation, stress response regulators control specific steps of the phospholipid synthesis pathway. We wanted to identify a potential regulator controlling the expression of the phosphatidylserine synthase gene. We showed that it was not the previously suggested
hdfR
gene and instead that a mutation in the anti-Shine-Dalgarno sequence of 16S RNA was responsible for an increase in
pssA
translation. This example underlines the fact that gene expression can be modulated by means other than specific regulatory processes.
Recent Advances and Future Prospects in Bacterial and Archaeal Locomotion and Signal Transduction
Authors: Bardy Sonia L. , Briegel Ariane , Rainville Simon , Krell Tino 
Published: May 2017

ABSTRACTThe structure and function of two-component and chemotactic signaling and different aspects related to the motility of bacteria and archaea are key research areas in modern microbiology.Escherichia coliis the traditional model organism used to study chemotaxis signaling and motility. However, the recent study of a wide range of bacteria and even some archaea with different lifestyles has provided new insight into the ecophysiology of chemotaxis, which is essential for the establishment of different pathogens or beneficial bacteria in a host. The expanded range of model organisms has also permitted the study of chemosensory pathways unrelated to chemotaxis, multiple chemotaxis pathways within an organism, and new types of chemoreceptors. This research has greatly benefitted from technical advances in the field of cryomicroscopy, which continues to reveal with increasing resolution the complexity and diversity of large protein complexes like the flagellar motor or chemoreceptor arrays. In addition, sensitive instruments now allow an increasing number of experiments to be conducted at the single-cell level, thereby revealing information that is beginning to bridge the gap between individual cells and population behavior. Evidence has also accumulated showing that bacteria have evolved different mechanisms for surface sensing, which appears to be mediated by flagella and possibly type IV pili, and that the downstream signaling involves chemosensory pathways and two-component-system-based processes. Herein, we summarize the recent advances and research tendencies in this field as presented at the latest Bacterial Locomotion and Signal Transduction (BLAST XIV) conference.
Ready or Not: Microbial Adaptive Responses in Dynamic Symbiosis Environments
Authors: Cao Mengyi , Goodrich-Blair Heidi 
Published: May 2017

ABSTRACTIn mutually beneficial and pathogenic symbiotic associations, microbes must adapt to the host environment for optimal fitness. Both within an individual host and during transmission between hosts, microbes are exposed to temporal and spatial variation in environmental conditions. The phenomenon of phenotypic variation, in which different subpopulations of cells express distinctive and potentially adaptive characteristics, can contribute to microbial adaptation to a lifestyle that includes rapidly changing environments. The environments experienced by a symbiotic microbe during its life history can be erratic or predictable, and each can impact the evolution of adaptive responses. In particular, the predictability of a rhythmic or cyclical series of environments may promote the evolution of signal transduction cascades that allow preadaptive responses to environments that are likely to be encountered in the future, a phenomenon known as adaptive prediction. In this review, we summarize environmental variations known to occur in some well-studied models of symbiosis and how these may contribute to the evolution of microbial population heterogeneity and anticipatory behavior. We provide details about the symbiosis betweenXenorhabdusbacteria andSteinernemanematodes as a model to investigate the concept of environmental adaptation and adaptive prediction in a microbial symbiosis.
Prophylactic use of eculizumab during surgery in chronic cold agglutinin disease
Authors: Tjønnfjord Eirik , Vengen Øystein A , Berentsen Sigbjørn , Tjønnfjord Geir Erland 
Published: May 2017

Primary chronic cold agglutinin disease (CAD) is an autoimmune haemolytic anaemia in which a specific bone marrow lymphoproliferative disorder causes production of cold agglutinins (CA). Binding of CA to erythrocyte surface antigens results in a predominantly extravascular haemolysis that is entirely complement dependent. Because of complement activation, exacerbations are common during febrile infections, trauma or major surgery. Involvement of the terminal complement pathway with C5-mediated intravascular haemolysis is probably not prominent in stable disease but is supposed to be of importance in exacerbations following acute phase reaction.We report on a patient with CAD prone to exacerbation of haemolysis during acute phase reactions who was scheduled for cardiac surgery. To prevent her having an exacerbation of haemolysis, we chose to treat her prophylactically with eculizumab along with the usual perioperative precautions. Aortic valve replacement was undertaken with full cardiopulmonary bypass at normothermia. The procedure was successful; no exacerbation of haemolysis was observed, and transfusion requirements did not exceed what could be expected.
A Rohingya refugee’s journey in Australia and the barriers to accessing healthcare
Authors: Jiwrajka Manasi , Mahmoud Ahmad , Uppal Maneeta 
Published: May 2017

Australia’s processing of some asylum seekers on offshore detention centres has recently been brought to light by human rights organisation. While the internal politics of resettling refugees may be complex, Australia remains in the top five countries for resettlement per capita. However, these refugees remain a vulnerable patient population after immigrating. Refugee women, an understudied group, in particular experience higher adverse health outcomes.In this case report, we follow the medical journey of KB, a 38-year-old Rohingya refugee diagnosed with type 2 diabetes mellitus—the crux of all her health issues. We explore language differences as a barrier to healthcare and its near-fatal consequences, as well as communication breakdown in the context of the misalignment of health goals between the patient and the profession. As such, improving patient health literacy and cultural competency among doctors are core interventions in improving the delivery of refugee healthcare.We have a global responsibility to improve health literacy among refugee patients and by providing the basic standard of healthcare to every individual as a human right, which empower refugees in this regard to have a role in their health outcomes.
Type 2 diabetes patient’s perspective on Ramadan fasting: a qualitative study
Authors: Lee Jun Yang , Wong Chee Piau , Tan Christina San San , Nasir Nazrila Hairizan , Lee Shaun Wen Huey 
Published: May 2017

ObjectiveWe evaluated the beliefs, experience and diabetes management strategies of type 2 diabetes mellitus (T2DM) Muslim patients that chose to fast during Ramadan.Research design and methodsA semistructured focus group interview was conducted with 53 participants with T2DM. Participants were purposefully sampled and asked to share their perspective on Ramadan fasting. All interviews were audio recorded, transcribed verbatim and analyzed thematically.ResultsParticipants reported optimism towards fasting during Ramadan, as they believed that fasting was beneficial to their overall well-being, and a time for family bonding. Most participants made limited attempts to discuss with their doctors on the decision to fast and self-adjusted their medication based on experience and symptoms during this period. They also reported difficulty in managing their diet, due to fear of hypoglycemia and the collective social aspect of fasting.ConclusionMuslims are optimistic about their well-being when fasting during Ramadan. Many choose to fulfill their religious obligation despite being discouraged by their doctors. Collaboration with religious authorities should be explored to ensure patients receive adequate education before fasting during Ramadan.Trial registration numberNCT02189135; Results.
Manual ventilation and open suction procedures contribute to negative pressures in a mechanical lung model
Authors: Nakstad Espen Rostrup , Opdahl Helge , Heyerdahl Fridtjof , Borchsenius Fredrik , Skjønsberg Ole Henning 
Published: May 2017

IntroductionRemoval of pulmonary secretions in mechanically ventilated patients usually requires suction with closed catheter systems or flexible bronchoscopes. Manual ventilation is occasionally performed during such procedures if clinicians suspect inadequate ventilation. Suctioning can also be performed with the ventilator entirely disconnected from the endotracheal tube (ETT). The aim of this study was to investigate if these two procedures generate negative airway pressures, which may contribute to atelectasis.MethodsThe effects of device insertion and suctioning in ETTs were examined in a mechanical lung model with a pressure transducer inserted distal to ETTs of 9 mm, 8 mm and 7 mm internal diameter (ID). A 16 Fr bronchoscope and 12, 14 and 16 Fr suction catheters were used at two different vacuum levels during manual ventilation and with the ETTs disconnected.ResultsDuring manual ventilation with ETTs of 9 mm, 8 mm and 7 mm ID, and bronchoscopic suctioning at moderate suction level, peak pressure (PPEAK) dropped from 23, 22 and 24.5 cm H2O to 16, 16 and 15 cm H2O, respectively. Maximum suction reduced PPEAKto 20, 17 and 11 cm H2O, respectively, and the end-expiratory pressure fell from 5, 5.5 and 4.5 cm H2O to –2, –6 and –17 cm H2O. Suctioning through disconnected ETTs (open suction procedure) gave negative model airway pressures throughout the duration of the procedures.ConclusionsManual ventilation and open suction procedures induce negative end-expiratory pressure during endotracheal suctioning, which may have clinical implications in patients who need high PEEP (positive end-expiratory pressure).
Validation of the Global Physical Activity Questionnaire for self-administration in a European context
Authors: Wanner Miriam , Hartmann Christina , Pestoni Giulia , Martin Brian Winfried , Siegrist Michael , Martin-Diener Eva 
Published: May 2017

Background/aimLittle is known about the measurement properties of the self-administered Global Physical Activity Questionnaire (GPAQ) in Europe. The aim was to validate the self-administered GPAQ against accelerometry in Switzerland in German, French and Italian.MethodsParticipants of this cross-sectional study were recruited among members of the Swiss Food Panel (German-speaking and French-speaking samples) and as a convenience sample (Italian-speaking sample). They completed the GPAQ and wore an Actigraph GT3X+ accelerometer during 7 days in 2014/2015. GPAQ and accelerometer data on total physical activity and different intensities, as well as sitting time, were compared using Spearman correlations and Bland-Altman plots.ResultsComplete data were available for 354 participants (50.6% women, mean age: 47.0 years) on physical activity, and for 366 on sitting time. Correlations were highest for vigorous physical activity (r=0.46) and sitting time (r=0.47). A significant sex difference was apparent for vigorous physical activity (men: r=0.35 vs women: r=0.55; p=0.02). Some age differences were present especially for total physical activity, with the lowest correlations found for those aged 60+ years. The correlation for sitting time was significantly higher in the youngest age group (r=0.61) compared with the middle (r=0.38, p=0.01) and the oldest age groups (r=0.37, p=0.03). Total physical activity was 2.8 times higher according to the GPAQ than to accelerometer data.ConclusionsThe self-administered version of the GPAQ showed fair-to-moderate validity in the three languages tested, both for men and women and individuals aged ≤60 years. For older individuals, a careful interpretation of total physical activity is required.