bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing the Antimicrobial Activity of Nisin-Based Lantibiotics against Gram-Negative Pathogens
Authors: Li Qian , Montalban-Lopez Manuel , Kuipers Oscar P. 
Published: April 2018

ABSTRACT

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial compounds containing lanthionine and methyl-lanthionine residues. Nisin, one of the most extensively studied and used lantibiotics, has been shown to display very potent activity against Gram-positive bacteria, and stable resistance is rarely observed. By binding to lipid II and forming pores in the membrane, nisin can cause the efflux of cellular constituents and inhibit cell wall biosynthesis. However, the activity of nisin against Gram-negative bacteria is much lower than that against Gram-positive bacteria, mainly because lipid II is located at the inner membrane, and the rather impermeable outer membrane in Gram-negative bacteria prevents nisin from reaching lipid II. Thus, if the outer membrane-traversing efficiency of nisin could be increased, the activity against Gram-negative bacteria could, in principle, be enhanced. In this work, several relatively short peptides with activity against Gram-negative bacteria were selected from literature data to be fused as tails to the C terminus of either full or truncated nisin species. Among these, we found that one of three tails (tail 2 [T2; DKYLPRPRPV], T6 [NGVQPKY], and T8 [KIAKVALKAL]) attached to a part of nisin displayed improved activity against Gram-negative microorganisms. Next, we rationally designed and reengineered the most promising fusion peptides. Several mutants whose activity significantly outperformed that of nisin against Gram-negative pathogens were obtained. The activity of the tail 16 mutant 2 (T16m2) construct against several important Gram-negative pathogens (i.e.,
Escherichia coli
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
,
Enterobacter aerogenes
) was increased 4- to 12-fold compared to that of nisin. This study indicates that the rational design of nisin can selectively and significantly improve its outer membrane-permeating capacity as well as its activity against Gram-negative pathogens.

IMPORTANCE
Lantibiotics are antimicrobial peptides that are highly active against Gram-positive bacteria but that have relatively poor activity against most Gram-negative bacteria. Here, we modified the model lantibiotic nisin by fusing parts of it to antimicrobial peptides with known activity against Gram-negative bacteria. The appropriate selection of peptidic moieties that could be attached to (parts of) nisin could lead to a significant increase in its inhibitory activity against Gram-negative bacteria. Using this strategy, hybrids that outperformed nisin by displaying 4- to 12-fold higher levels of activity against relevant Gram-negative bacterial species were produced. This study shows the power of modified peptide engineering to alter target specificity in a desired direction.
Efficacy of Silver Dihydrogen Citrate and Steam Vapor against a Human Norovirus Surrogate, Feline Calicivirus, in Suspension, on Glass, and on Carpet
Authors: Buckley David , Dharmasena Muthu , Fraser Angela , Pettigrew Charles , Anderson Jeffery , Jiang Xiuping 
Published: April 2018

ABSTRACT

Carpets and other soft surfaces have been associated with prolonged and reoccurring human norovirus (HuNoV) outbreaks. Environmental hygiene programs are important to prevent and control HuNoV outbreaks. Despite our knowledge of HuNoV transmission via soft surfaces, no commercially available disinfectants have been evaluated on carpets. Our aim was to adapt a current standardized method for virucidal testing by assessing two disinfection technologies, silver dihydrogen citrate (SDC) and steam vapor, against one HuNoV surrogate, feline calicivirus (FCV), on wool and nylon carpets. First, we evaluated the effect of both technologies on the appearance of carpet. Next, we evaluated the efficacy of SDC in suspension and the efficacy of SDC and steam vapor against FCV on a glass surface, each with and without serum. Lastly, we tested both technologies on two types of carpet, wool and nylon. Both carpets exhibited no obvious color changes; however, SDC treatments left a residue while steam vapor left minor abrasions to fibers. SDC in suspension and on glass reduced FCV by 4.65 log
10
and >4.66 log
10
PFU, respectively, but demonstrated reduced efficacy in the presence of serum. However, SDC was only efficacious against FCV on nylon (3.62-log
10
PFU reduction) and not wool (1.82-log
10
PFU reduction). Steam vapor reduced FCV by >4.93 log
10
PFU on glass in 10 s and >3.68 log
10
PFU on wool and nylon carpet carriers in 90 s. There was a limited reduction of FCV RNA under both treatments compared to that of infectivity assays, but RNA reductions were higher in samples that contained serum.

IMPORTANCE
Human noroviruses (HuNoV) account for ca. 20% of all diarrheal cases worldwide. Disease symptoms may include diarrhea and vomit, with both known to contribute to transmission. The prevention and control of HuNoV are difficult because they are environmentally resilient and resistant to many disinfectants. Several field studies have linked both hard and soft surfaces to HuNoV outbreaks. However, many disinfectants efficacious against HuNoV surrogates are recommended for hard surfaces, but no commercially available products have demonstrated efficacy against these surrogates on soft surfaces. Our research objectives were to evaluate liquid and steam-based technologies in suspension and on hard surface carriers in addition to adapting and testing a protocol for assessing the virucidal effects of disinfection technologies on carpet carriers. These results will inform both the government and industry regarding a standard method for evaluating the virucidal effects of disinfectants on carpet while demonstrating their efficacy relative to suspension and hard-surface tests.
Endoribonuclease YbeY Is Linked to Proper Cellular Morphology and Virulence in Brucella abortus
Authors: Budnick James A. , Sheehan Lauren M. , Colquhoun Jennifer M. , Dunman Paul M. , Walker Graham C. , Roop R. Martin , Caswell Clayton C. 
Published: April 2018

ABSTRACT

The YbeY endoribonuclease is one of the best-conserved proteins across the kingdoms of life. In the present study, we demonstrated that YbeY in
Brucella abortus
is linked to a variety of important activities, including proper cellular morphology, mRNA transcript levels, and virulence. Deletion of
ybeY
in
B. abortus
led to a small-colony phenotype when the bacteria were grown on agar medium, as well as to significant aberrations in the morphology of the bacterial cell as evidenced by electron microscopy. Additionally, compared to the parental strain, the Δ
ybeY
strain was significantly attenuated in both macrophage and mouse models of infection. The Δ
ybeY
strain also showed increased sensitivities to several
in vitro
-applied stressors, including bile acid, hydrogen peroxide, SDS, and paraquat. Transcriptomic analysis revealed that a multitude of mRNA transcripts are dysregulated in the Δ
ybeY
strain, and many of the identified mRNAs encode proteins involved in metabolism, nutrient transport, transcriptional regulation, and flagellum synthesis. We subsequently constructed gene deletion strains of the most highly dysregulated systems, and several of the YbeY-linked gene deletion strains exhibited defects in the ability of the bacteria to survive and replicate in primary murine macrophages. Taken together, these data establish a clear role for YbeY in the biology and virulence of
Brucella
; moreover, this work further illuminates the highly varied roles of this widely conserved endoribonuclease in bacteria.

IMPORTANCE
Brucella
spp. are highly efficient bacterial pathogens of animals and humans, causing significant morbidity and economic loss worldwide, and relapse of disease often occurs following antibiotic treatment of human brucellosis. As such, novel therapeutic strategies to combat
Brucella
infections are needed. Ribonucleases in the brucellae are understudied, and these enzymes represent elements that may be potential targets for future treatment approaches. The present work demonstrates the importance of the YbeY endoribonuclease for cellular morphology, efficient control of mRNA levels, and virulence in
B. abortus
. Overall, the results of this study advance our understanding of the critical roles of YbeY in the pathogenesis of the intracellular brucellae and expand our understanding of this highly conserved RNase.
Diagnostic Performance of a Molecular Test versus Clinician Assessment of Vaginitis
Authors: Schwebke Jane R. , Gaydos Charlotte A. , Nyirjesy Paul , Paradis Sonia , Kodsi Salma , Cooper Charles K. 
Published: April 2018

ABSTRACT

Vaginitis is a common complaint, diagnosed either empirically or using Amsel's criteria and wet mount microscopy. This study sought to determine characteristics of an investigational test (a molecular test for vaginitis), compared to reference, for detection of bacterial vaginosis,
Candida
spp., and
Trichomonas vaginalis
. Vaginal specimens from a cross-sectional study were obtained from 1,740 women (≥18 years old), with vaginitis symptoms, during routine clinic visits (across 10 sites in the United States). Specimens were analyzed using a commercial PCR/fluorogenic probe-based investigational test that detects bacterial vaginosis,
Candida
spp., and
Trichomonas vaginalis
. Clinician diagnosis and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet mount) were also employed to detect the three vaginitis causes. All testing methods were compared to the respective reference methods (Nugent Gram stain for bacterial vaginosis, detection of the
Candida
gene
its2
, and
Trichomonas vaginalis
culture). The investigational test, clinician diagnosis, and in-clinic testing were compared to reference methods for bacterial vaginosis,
Candida
spp., and
Trichomonas vaginalis
. The investigational test resulted in significantly higher sensitivity and negative predictive value than clinician diagnosis or in-clinic testing. In addition, the investigational test showed a statistically higher overall percent agreement with each of the three reference methods than did clinician diagnosis or in-clinic testing. The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis.
Effect of emotional content on online video sharing among health care professionals and researchers (DIFFUSION): results and lessons learnt from a randomised controlled trial
Authors: Kiriya Junko , Edwards Phil , Roberts Ian 
Published: April 2018

ObjectivesWe assessed the effect of emotional content on the extent to which online videos are shared among health professionals.SettingWe conducted a two-arm randomised controlled trial. We sent a link to one of two videos by email to participants asking them to watch the video and forward it to their colleagues.ParticipantsHealth professionals and researchers (obstetrics, gynaecology and midwifery) with an email address apart from those in countries where access to YouTube is banned. We estimated that 7000 participants were required.InterventionsWe compared two online videos providing background information about the WOMAN trial. The videos were the same length and had the same content. However, the intervention video had more emotional impact than the control video.Outcome measuresThe primary outcome was video sharing and the secondary outcome was views generated by participants. We conducted a χ2test for the primary outcome and t-test for the secondary outcome.ResultsWe randomly allocated 8353 email addresses, 4178 to the intervention video and 4175 to the control. Of these, 221 (5.3%) watched the intervention video and 215 (5.1%) watched the control. In the intervention group, 44 (1.1%) forwarded the video compared with 37 (0.9%) in the control group (risk ratio 1.2 [95% CI 0.8 to 1.8], p=0.44). Mean number of views generated by participants allocated to the intervention video was 0.04 and the control video was 0.03 (mean difference 0.01 [95% CI −0.02 to 0.04], p=0.53).ConclusionsWe found no evidence that emotional content increased forwarding. The trial had low power due to the low video watching rate and the small number of outcome events. A key challenge for online dissemination is ensuring recipients watch the video.Trial registration numberNCT02109159; Results.
Using the Oxford Foot Model to determine the association between objective measures of foot function and results of the AOFAS Ankle-Hindfoot Scale and the Foot Function Index: a prospective gait analysis study in Germany
Authors: Kostuj Tanja , Stief Felix , Hartmann Kirsten Anna , Schaper Katharina , Arabmotlagh Mohammad , Baums Mike H , Meurer Andrea , Krummenauer Frank , Lieske Sebastian 
Published: April 2018

ObjectiveAfter cross-cultural adaption for the German translation of the Ankle-Hindfoot Scale of the American Orthopaedic Foot and Ankle Society (AOFAS-AHS) and agreement analysis with the Foot Function Index (FFI-D), the following gait analysis study using the Oxford Foot Model (OFM) was carried out to show which of the two scores better correlates with objective gait dysfunction.Design and participantsResults of the AOFAS-AHS and FFI-D, as well as data from three-dimensional gait analysis were collected from 20 patients with mild to severe ankle and hindfoot pathologies.Kinematic and kinetic gait data were correlated with the results of the total AOFAS scale and FFI-D as well as the results of those items representing hindfoot function in the AOFAS-AHS assessment. With respect to the foot disorders in our patients (osteoarthritis and prearthritic conditions), we correlated the total range of motion (ROM) in the ankle and subtalar joints as identified by the OFM with values identified during clinical examination ‘translated’ into score values. Furthermore, reduced walking speed, reduced step length and reduced maximum ankle power generation during push-off were taken into account and correlated to gait abnormalities described in the scores. An analysis of correlations with CIs between the FFI-D and the AOFAS-AHS items and the gait parameters was performed by means of the Jonckheere-Terpstra test; furthermore, exploratory factor analysis was applied to identify common information structures and thereby redundancy in the FFI-D and the AOFAS-AHS items.ResultsObjective findings for hindfoot disorders, namely a reduced ROM, in the ankle and subtalar joints, respectively, as well as reduced ankle power generation during push-off, showed a better correlation with the AOFAS-AHS total score—as well as AOFAS-AHS items representing ROM in the ankle, subtalar joints and gait function—compared with the FFI-D score.Factor analysis, however, could not identify FFI-D items consistently related to these three indicator parameters (pain, disability and function) found in the AOFAS-AHS. Furthermore, factor analysis did not support stratification of the FFI-D into two subscales.ConclusionsThe AOFAS-AHS showed a good agreement with objective gait parameters and is therefore better suited to evaluate disability and functional limitations of patients suffering from foot and ankle pathologies compared with the FFI-D.
Access to palliative care by disease trajectory: a population-based cohort of Ontario decedents
Authors: Seow Hsien , O’Leary Erin , Perez Richard , Tanuseputro Peter 
Published: April 2018

ObjectivesTo examine access to palliative care between different disease trajectories and compare to other geographic areas.DesignA retrospective population-based decedent cohort study using linked administrative data.SettingOntario, Canada.ParticipantsOntario decedents between 1 April 2010 and 31 December 2012. Patients were categorised into disease trajectories: terminal illness (eg, cancer), organ failure (eg, chronic heart failure), frailty (eg, dementia), sudden death or other.InterventionsReceipt of palliative care services from institutional and community settings, derived from a validated list of palliative care codes from multiple administrate databases.Outcome measuresReceiving any palliative care services in the last year of life (yes/no), intensity (total days) and time of initiation of palliative care, in hospital and community sectors. Multivariable analysis examined the association between disease trajectory and the receipt of palliative care in the last year of life.ResultsWe identified 235 159 decedents in Ontario. In the last year of life, 88% of terminal illness, 44% of organ failure and 32% of frailty decedents accessed at least one palliative care service. Most care was provided during an inpatient hospitalisation. Terminal illness decedents received twice as many palliative care days (mean of 49 days) compared with organ failure and frailty decedents. Patients with terminal illness initiated palliative care median of 107 days before death compared with median of 19 days among those using the US Medicare hospice benefit.ConclusionsTerminal illness decedents are more likely to receive any palliative care, with increased intensity and earlier before death than organ failure or frailty decedents. These data serve as a useful comparison for other countries with similar and different healthcare systems and eligibility criteria.
Collection and sharing of medical information and medical intelligence (M2I) in NATO: a transversal survey
Authors: Bedubourg Gabriel , Wiik H , Queyriaux B , Lausund P , Meynard J-B 
Published: April 2018

IntroductionThere is a requirement for adequate medical expertise to be available throughout the range of potential future operations involving members of the North Atlantic Treaty Organization (NATO). The aim of this study was to assess the collection and sharing of medical intelligence and medical information (M2I) by NATO Nations, Partner Nations and NATO Command Structure and NATO Force Structure Headquarters (NCS/NFS HQs).Materials and methodsA transversal survey was conducted between December 2014 and March 2015 using a survey form on M2I sent to NATO Nations and Partnership for Peace (PfP) Nations as well as NCS/NFS HQs.ResultsCorrectly completed responses were received from 15/40 (37.5%) of the possible NATO and PfP Nations (37.5%) and 7/8 (87.5%) of the NCS/NFS HQs (100.0%). Deficiencies in the collection of M2I data were found due to lack of specific doctrines, networks, tools, structures and organisation.ConclusionsThe survey provided an indication even though the participation rate was low for Nations. Part of the problem is thought to be that medical information and medical intelligence often lie in different chains of command. Future directions for this research could include studying the possibilities of a new specific information technology (IT) system to collect and to share M2I. Collection and sharing of M2I within the NATO/PfP community requires facilitation in order to strengthen the basis for decision-making and force health protection. The development of a dedicated NATO IT system may be a precondition for the implementation of an efficient M2I network.
Risk factors for lower limb injuries during initial naval training: a prospective study
Authors: Bonanno Daniel R , Munteanu S E , Murley G S , Landorf K B , Menz H B 
Published: April 2018

IntroductionThis study aimed to identify risk factors associated with the development of common lower limb injuries during initial defence training in naval recruits who were enrolled in a randomised trial.MethodsThree-hundred and six naval recruits were randomly allocated flat insoles (n=153) or foot orthoses (n=153) while undertaking 11 weeks of initial training. Participant characteristics (including anthropometrics, general health, physical activity, fitness and foot characteristics) were collected at the baseline assessment and injuries were documented prospectively. Injury was defined as the combined incidence of participants with medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain throughout the 11 weeks of training. A discriminant function analysis was used to explore the ability of baseline measures to predict injury.ResultsOverall, 67 (21.9%) participants developed an injury. Discriminant function analysis revealed that participants who sustained an injury were slightly younger (mean 21.4±SD 4.1 vs 22.5±5.0 years) and were less likely to be allocated to the foot orthosis group (40% vs 53%) compared with those who remained uninjured. The accuracy of these baseline variables to predict injury was moderate (78.1%).ConclusionsLower limb injury was not accurately predicted from health questionnaires, fitness results and clinical assessments in naval recruits undertaking initial defence training. However, although not reaching statistical significance, the use of foot orthoses may be protective against common lower limb injuries.Trial registration numberACTRN12615000024549; Post-results.
Klf4 has an unexpected protective role in perivascular cells within the microvasculature
Authors: Haskins Ryan M. , Nguyen Anh T. , Alencar Gabriel F. , Billaud Marie , Kelly-Goss Molly R. , Good Miranda E. , Bottermann Katharina , Klibanov Alexander L. , French Brent A. , Harris Thurl E. , Peirce Shayn M. , Isakson Brant E. , Owens Gary K. 
Published: April 2018

Recent smooth muscle cell (SMC) lineage-tracing studies have revealed that SMCs undergo remarkable changes in phenotype during development of atherosclerosis. Of major interest, we demonstrated that Kruppel-like factor 4 (KLF4) in SMCs is detrimental for overall lesion pathogenesis, in that SMC-specific conditional knockout of the KLF4 gene ( Klf4) resulted in smaller, more-stable lesions that exhibited marked reductions in the numbers of SMC-derived macrophage- and mesenchymal stem cell-like cells. However, since the clinical consequences of atherosclerosis typically occur well after our reproductive years, we sought to identify beneficial KLF4-dependent SMC functions that were likely to be evolutionarily conserved. We tested the hypothesis that KLF4-dependent SMC transitions play an important role in the tissue injury-repair process. Using SMC-specific lineage-tracing mice positive and negative for simultaneous SMC-specific conditional knockout of Klf4, we demonstrate that SMCs in the remodeling heart after ischemia-reperfusion injury (IRI) express KLF4 and transition to a KLF4-dependent macrophage-like state and a KLF4-independent myofibroblast-like state. Moreover, heart failure after IRI was exacerbated in SMC Klf4 knockout mice. Surprisingly, we observed a significant cardiac dilation in SMC Klf4 knockout mice before IRI as well as a reduction in peripheral resistance. KLF4 chromatin immunoprecipitation-sequencing analysis on mesenteric vascular beds identified potential baseline SMC KLF4 target genes in numerous pathways, including PDGF and FGF. Moreover, microvascular tissue beds in SMC Klf4 knockout mice had gaps in lineage-traced SMC coverage along the resistance arteries and exhibited increased permeability. Together, these results provide novel evidence that Klf4 has a critical maintenance role within microvascular SMCs: it is required for normal SMC function and coverage of resistance arteries. NEW & NOTEWORTHY We report novel evidence that the Kruppel-like factor 4 gene ( Klf4) has a critical maintenance role within microvascular smooth muscle cells (SMCs). SMC-specific Klf4 knockout at baseline resulted in a loss of lineage-traced SMC coverage of resistance arteries, dilation of resistance arteries, increased blood flow, and cardiac dilation.