bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing
Enterobacteriaceae
, 2010 to 2014
Authors: Mataseje Laura F. , Abdesselam Kahina , Vachon Julie , Mitchel Robyn , Bryce Elizabeth , Roscoe Diane , Boyd David A. , Embree Joanne , Katz Kevin , Kibsey Pamela , Simor Andrew E. , Taylor Geoffrey , Turgeon Nathalie , Langley Joanne , Gravel Denise , Amaratunga Kanchana , Mulvey Michael R. 
Published: September 2016

ABSTRACT

Carbapenemase-producing
Enterobacteriaceae
(CPE) are increasing globally; here we report on the investigation of CPE in Canada over a 5-year period. Participating acute care facilities across Canada submitted carbapenem-nonsusceptible
Enterobacteriaceae
from 1 January 2010 to 31 December 2014 to the National Microbiology Laboratory. All CPE were characterized by antimicrobial susceptibilities, pulsed-field gel electrophoresis, multilocus sequence typing, and plasmid restriction fragment length polymorphism analysis and had patient data collected using a standard questionnaire. The 5-year incidence rate of CPE was 0.09 per 10,000 patient days and 0.07 per 1,000 admissions. There were a total of 261 CPE isolated from 238 patients in 58 hospitals during the study period.
bla
KPC-3
(64.8%) and
bla
NDM-1
(17.6%) represented the highest proportion of carbapenemase genes detected in Canadian isolates. Patients who had a history of medical attention during international travel accounted for 21% of CPE cases. The hospital 30-day all-cause mortality rate for the 5-year surveillance period was 17.1 per 100 CPE cases. No significant increase in the occurrence of CPE was observed from 2010 to 2014. Nosocomial transmission of CPE, as well as international health care, is driving its persistence within Canada.
MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells
Authors: Chen Steven C. Y. , Constantinides Christos , Kebschull Moritz , Papapanou Panos N. 
Published: September 2016

ABSTRACT

MicroRNAs (miRNAs) have been established as key regulators of various biological processes with possible involvement in the pathobiology of periodontal disease. Expanding our earlier observations of substantial differential expression of specific miRNAs between clinically healthy and periodontitis-affected gingival tissues, we used miRNA inhibitors (sponges) in loss-of-function experiments to investigate the involvement of specific miRNAs in the response of pocket epithelium-derived, telomerase-immortalized human gingival keratinocytes (TIGKs) to microbial infection. We constructed stable knockdown (KD) cell lines for five epithelium-expressed miRNAs (miR-126, miR-141, miR-155, miR-210, and miR-1246) and assessed their response to infection with periodontal pathogens using microarray analysis, quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot assay. miR-126 KD cells showed lower expression of interleukin 8 (IL-8) and CXCL1, both on the mRNA and protein levels, than did controls upon stimulation by heat-killed wild-type
Porphyromonas gingivalis
, live
P. gingivalis
protease-deficient mutant KDP128, and live
Aggregatibacter actinomycetemcomitans
. In contrast, infection of miR-155 KD and miR-210 KD cells with the same organisms resulted in higher IL-8 and CXCL1 mRNA and protein expression. These effects appeared to be regulated by NF-κB, as suggested by altered transcription and/or phosphorylation status of components of the NF-κB system. Reduced neutrophil-like HL-60 cell chemotactic activity was observed in response to infection of miR-126 KD cells, indicating that miR-126 plays an important role in immune responses. Our findings indicate that specific miRNAs regulate the expression of inflammatory cytokines in human gingival epithelial cells in response to microbial infection.
Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion
Authors: Smith Carol , Stringer Anne M. , Mao Chunhong , Palumbo Michael J. , Wade Joseph T. 
Published: September 2016

ABSTRACT

Salmonella enterica
pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs. However, very few of the regulatory targets are known for these TFs, and the extent of the regulatory network is unclear. In this study, we used complementary genomic approaches to map the direct regulatory targets of all 7 TFs. Our data reveal a highly complex and interconnected network that includes many previously undescribed regulatory targets. Moreover, the network extends well beyond the 7 TFs, due to the inclusion of many additional TFs and noncoding RNAs. By comparing gene expression profiles of regulatory targets for the 7 TFs, we identified many uncharacterized genes that are likely to play direct roles in invasion. We also uncovered cross talk between SPI-1 regulation and other regulatory pathways, which, in turn, identified gene clusters that likely share related functions. Our data are freely available through an intuitive online browser and represent a valuable resource for the bacterial research community.

IMPORTANCE
Invasion of epithelial cells is an early step during infection by
Salmonella enterica
and requires secretion of specific proteins into host cells via a type III secretion system (T3SS). Most T3SS-associated proteins required for invasion are encoded in a horizontally acquired genomic locus known as
Salmonella
pathogenicity island 1 (SPI-1). Multiple regulators respond to environmental signals to ensure appropriate timing of SPI-1 gene expression. In particular, there are seven transcription regulators that are known to be involved in coordinating expression of SPI-1 genes. We have used complementary genome-scale approaches to map the gene targets of these seven regulators. Our data reveal a highly complex and interconnected regulatory network that includes many previously undescribed target genes. Moreover, our data functionally implicate many uncharacterized genes in the invasion process and reveal cross talk between SPI-1 regulation and other regulatory pathways. All datasets are freely available through an intuitive online browser.
aroA
-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant
Authors: Felgner Sebastian , Frahm Michael , Kocijancic Dino , Rohde Manfred , Eckweiler Denitsa , Bielecka Agata , Bueno Emilio , Cava Felipe , Abraham Wolf-Rainer , Curtiss Roy , Häussler Susanne , Erhardt Marc , Weiss Siegfried 
Published: September 2016

ABSTRACT

Recombinant attenuated
Salmonella enterica
serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of
aroA
, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of
aroA
dramatically increased the virulence of attenuated
Salmonella
in mouse models. Mutant bacteria lacking
aroA
elicited increased levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) after systemic application
.
A detailed genetic and phenotypic characterization in combination with transcriptomic and metabolic profiling demonstrated that Δ
aroA
mutants display pleiotropic alterations in cellular physiology and lipid and amino acid metabolism, as well as increased sensitivity to penicillin, complement, and phagocytic uptake. In concert with other immunomodulating mutations, deletion of
aroA
affected flagellin phase variation and gene expression of the virulence-associated genes
arnT
and
ansB
. Finally,
ΔaroA
strains displayed significantly improved tumor therapeutic activity. These results highlight the importance of a functional shikimate pathway to control homeostatic bacterial physiology. They further highlight the great potential of
ΔaroA
-attenuated
Salmonella
for the development of vaccines and cancer therapies with important implications for host-pathogen interactions and translational medicine.

IMPORTANCE
Recombinant attenuated bacterial vector systems based on genetically engineered
Salmonella
have been developed as highly potent vaccines. Due to the pathogenic properties of
Salmonella
, efficient attenuation is required for clinical applications. Since the hallmark study by Hoiseth and Stocker in 1981 (S. K. Hoiseth and B. A. D. Stocker, Nature 291:238–239, 1981, http://dx.doi.org/10.1038/291238a0), the auxotrophic Δ
aroA
mutation has been generally considered safe and universally used to attenuate bacterial strains. Here, we are presenting the remarkable finding that a deletion of
aroA
leads to pronounced alterations of gene expression, metabolism, and cellular physiology, which resulted in increased immunogenicity, virulence, and adjuvant potential of
Salmonella.
These results suggest that the enhanced immunogenicity of
aroA
-deficient
Salmonella
strains might be advantageous for optimizing bacterial vaccine carriers and immunotherapy. Accordingly, we demonstrate a superior performance of Δ
aroA Salmonella
in bacterium-mediated tumor therapy. In addition, the present study highlights the importance of a functional shikimate pathway to sustain bacterial physiology and metabolism.
Complete and Incomplete Genome Packaging of Influenza A and B Viruses
Authors: Nakatsu Sumiho , Sagara Hiroshi , Sakai-Tagawa Yuko , Sugaya Norio , Noda Takeshi , Kawaoka Yoshihiro 
Published: September 2016

ABSTRACT
The genomes of influenza A and B viruses comprise eight segmented, single-stranded, negative-sense viral RNAs (vRNAs). Although segmentation of the virus genome complicates the packaging of infectious progeny into virions, it provides an evolutionary benefit in that it allows viruses to exchange vRNAs with other strains. Influenza A viruses are believed to package their eight different vRNAs in a specific manner. However, several studies have shown that many viruses are noninfectious and fail to package at least one vRNA. Therefore, the genome-packaging mechanism is not fully understood. In this study, we used electron microscopy to count the number of ribonucleoproteins (RNPs) inside the virions of different influenza A and B virus strains. All eight strains examined displayed eight RNPs arranged in a “7+1” configuration in which a central RNP was surrounded by seven RNPs. Three-dimensional analysis of the virions showed that at least 80% of the virions packaged all eight RNPs; however, some virions packaged only five to seven RNPs, with the exact proportion depending on the strain examined. These results directly demonstrate that most viruses package eight RNPs, but some do indeed package fewer. Our findings support the selective genome-packaging model and demonstrate the variability in the number of RNPs incorporated by virions, suggesting that the genome-packaging mechanism of influenza viruses is more flexible than previously thought.

IMPORTANCE
The genomes of influenza A and B viruses contain segmented RNAs, which complicates genome packaging but provides the evolutionary advantage of allowing the exchange of individual genome segments with those of other strains. Some studies have shown that influenza A viruses package all eight genome segments in a specific manner, whereas others have shown that many virions are noninfectious and fail to package at least one genome segment. However, such viruses have never been directly observed. Here, we used electron microscopy to provide the first direct visual evidence of virions packaging an incomplete set of ribonucleoproteins. The percentage of these noninfectious virions varied from 0 to 20, depending on the virus strain, indicating that most virions package all eight genome segments. These results extend our knowledge about how infectious and noninfectious virions coordinate for successful virus infection.
Young female handball players and sport specialisation: how do they cope with the transition from primary school into a secondary sport school?
Authors: Kristiansen Elsa , Stensrud Trine 
Published: September 2016

ObjectiveThe aim of the present study was to examine how six young female handball players (aged 13–14 years) perceived the transition from primary school to a sport-specialised secondary school.MethodsPhysical and physiological data as well as data from questionnaires were collected at baseline and after the first year at the sport school, and qualitative interviews were performed retrospectively after the first year at school.ResultsEvidence of competition-related stressors, organisational stressors (sport and school balance) and personal stressors (social life and sport balance, lack of sleep and severe injuries) was found. Three girls developed long-lasting musculoskeletal injuries (>3 months out of ordinary training) and one experienced repeated short periods (≤2 weeks out of ordinary training) of injuries during the first year. Onset of menarche and a length growth between 6 and 8 cm during the first year were characteristic traits of the four injured girls.ConclusionsFrom our small study, it appears that young athletes attending a specialised secondary sport school experienced many stressors due to a significant increase in training volume, reduction in sleeping time and development of severe and long-lasting injuries. Hence, trainers at sport schools, club trainers and parents need to communicate and support them in order to prevent this.
Descriptive, cross-country analysis of the nurse practitioner workforce in six countries: size, growth, physician substitution potential
Authors: Maier Claudia B , Barnes Hilary , Aiken Linda H , Busse Reinhard 
Published: September 2016

ObjectivesMany countries are facing provider shortages and imbalances in primary care or are projecting shortfalls for the future, triggered by the rise in chronic diseases and multimorbidity. In order to assess the potential of nurse practitioners (NPs) in expanding access, we analysed the size, annual growth (2005–2015) and the extent of advanced practice of NPs in 6 Organisation for Economic Cooperation and Development (OECD) countries.DesignCross-country data analysis of national nursing registries, regulatory bodies, statistical offices data as well as OECD health workforce and population data, plus literature scoping review.Setting/participantsNP and physician workforces in 6 OECD countries (Australia, Canada, Ireland, the Netherlands, New Zealand and USA).Primary and secondary outcome measuresThe main outcomes were the absolute and relative number of NPs per 100 000 population compared with the nursing and physician workforces, the compound annual growth rates, annual and median percentage changes from 2005 to 2015 and a synthesis of the literature on the extent of advanced clinical practice measured by physician substitution effect.ResultsThe USA showed the highest absolute number of NPs and rate per population (40.5 per 100 000 population), followed by the Netherlands (12.6), Canada (9.8), Australia (4.4), and Ireland and New Zealand (3.1, respectively). Annual growth rates were high in all countries, ranging from annual compound rates of 6.1% in the USA to 27.8% in the Netherlands. Growth rates were between three and nine times higher compared with physicians. Finally, the empirical studies emanating from the literature scoping review suggested that NPs are able to provide 67–93% of all primary care services, yet, based on limited evidence.ConclusionsNPs are a rapidly growing workforce with high levels of advanced practice potential in primary care. Workforce monitoring based on accurate data is critical to inform educational capacity and workforce planning.
Randomised factorial mixed method pilot study of aerobic and resistance exercise in haemodialysis patients: DIALY-SIZE!
Authors: Thompson Stephanie , Klarenbach Scott , Molzahn Anita , Lloyd Anita , Gabrys Iwona , Haykowsky Mark , Tonelli Marcello 
Published: September 2016

ObjectivesFor people with end-stage renal disease requiring haemodialysis, exercise can improve aspects of quality of life (QoL). However, the relative benefits and risks of different types of exercise in this population are unknown. Therefore, this pilot study aimed to evaluate the feasibility of a main study evaluating the efficacy of cycling and resistance exercise each performed during the haemodialysis treatment on QoL.MethodsIn this factorial (2×2) pilot trial, 31 haemodialysis patients were randomised to cycling, resistance, cycling and resistance, or an attention control. Feasibility was defined a priori by criteria on recruitment, fidelity to the protocol and patient response to the intervention. To better understand feasibility, we conducted interviews with dialysis unit staff and trial participants. As secondary outcomes, we estimated the main effect of cycling and weights each compared with control on QoL, physical function and strength.FindingsWe exceeded the target accrual of 28 participants over 12 weeks. Irrespective of exercise group allocation, adherence was high; of the 1038 training sessions offered, 87% were initiated and over 80% of exercise sessions were performed as per protocol. Progression based on perceived exertion, individual instruction and interactions with the kinesiologist facilitated acceptability across exercise groups. Using an attention control, measures of contamination and attrition were low. Important barriers to unit staff readiness for the intervention were initial safety and workflow concerns, unit workload and onerous data collection. Secondary outcomes were not statistically significant. Adverse events were low and did not increase with a higher volume of exercise.ConclusionsThe main study is feasible with minor modifications. In addition to practical assistance, involvement from unit staff could increase patient participation and improve trial implementation. Strategies to increase acceptability of the intervention for staff include improving workflow integration and using a prestudy demonstration phase to introduce the intervention.Trial registration numberNCT02234232. Results
Diagnostic evaluation for autism spectrum disorder: a survey of health professionals in Australia
Authors: Taylor Lauren J , Eapen Valsamma , Maybery Murray T , Midford Sue , Paynter Jessica , Quarmby Lyndsay , Smith Timothy , Williams Katrina , Whitehouse Andrew J O 
Published: September 2016

ObjectivesThere is currently no agreed Australian standard for the diagnosis of autism spectrum disorder (ASD) even though there are specific diagnostic services available. We suspected inconsistency in the diagnostic practices of health professionals in Australia and aimed to assess these practices across the nation by surveying all relevant professional groups.DesignIn this study, we completed a survey of 173 health professionals whose clinical practice includes participating in the diagnostic process for ASD in Australia. Participants completed an online questionnaire which included questions about their diagnostic setting, diagnostic practice and diagnostic outcomes in 2014–2015.ParticipantsParticipants covered a range of disciplines including paediatrics, psychiatry, psychology, speech pathology and occupational therapy. All states and territories of Australia were represented.SettingParticipants came from a range of service settings which included hospitals, non-governmental organisations, publicly funded diagnostic services and private practice.ResultsThere was variability in diagnostic practices for ASD in Australia. While some clinicians work within a multidisciplinary assessment team, others practice independently and rarely collaborate with other clinicians to make a diagnostic decision. Only half of the respondents reported that they include a standardised objective assessment tool such as the Autism Diagnostic Observation Schedule in ASD assessments, and one-third indicated that they do not include measures of development, cognition and language in assessments where ASD is suspected.ConclusionsReported practice of some professionals in Australia may not be consistent with international best practice guidelines for ASD diagnosis. These findings highlight the need for a minimum national standard for ASD diagnosis throughout Australia that ensures best practice regardless of the type of setting in which the service is provided.
Induction maintenance with tumour necrosis factor-inhibitor combination therapy with discontinuation versus methotrexate monotherapy in early rheumatoid arthritis: a systematic review and meta-analysis of efficacy in randomised controlled trials
Authors: Emamikia Sharzad , Arkema Elizabeth V , Györi Noémi , Detert Jacqueline , Chatzidionysiou Katerina , Dougados Maxime , Burmester Gerd Rüdiger , van Vollenhoven Ronald 
Published: September 2016

ObjectiveTo determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with MTX monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn.MethodsWe performed a meta-analysis of trials using the initial combination of MTX+TNFi in conventional synthetic disease-modifying antirheumatic drug-naïve patients with early rheumatoid arthritis (RA). A systematic literature search was performed for induction-maintenance randomised controlled trials (RCTs) where initial combination therapy was compared with MTX monotherapy in patients with clinically active early RA. Our primary outcome was the proportion of patients who achieved low disease activity (LDA; Disease Activity Score (DAS)28<3.2) and/or remission (DAS28<2.6) at 12–76 weeks of follow-up. A random-effects model was used to pool the risk ratio (RR) for LDA and remission and heterogeneity was explored by subgroup analyses.ResultsWe identified 6 published RCTs, 4 of them where MTX+adalimumab was given as initial therapy and where adalimumab was withdrawn in a subset of patients after LDA/remission had been achieved. 2 additional trials used MTX+infliximab as combination therapy. The pooled RRs for achieving LDA and clinical remission at follow-up after withdrawal of TNFi were 1.41 (95% CI 1.05 to 1.89) and 1.34 (95% CI 0.95 to 1.89), respectively. There was significant heterogeneity between trials due to different treatment strategies, which was a limitation to this study.ConclusionsInitial therapy with MTX+TNFi is associated with a higher chance of retaining LDA and/or remission even after discontinuation of TNFi.
Contribution to modeling the viscosity Arrhenius-type equation for saturated pure fluids
Authors: Tian Jianxiang , Zhang Laibin 
Published: September 2016

Recently, Haj-Kacem et al. proposed an equation modeling the relationship between the two parameters of viscosity Arrhenius-type equations [Fluid Phase Equilibria 383, 11 (2014)]. The authors found that the two parameters are dependent upon each other in an exponential function form. In this paper, we reconsidered their ideas and calculated the two parameter values for 49 saturated pure fluids by using the experimental data in the NIST WebBook. Our conclusion is different with the ones of Haj-Kacem et al. We found that (the linearity shown by) the Arrhenius equation stands strongly only in low temperature range and that the two parameters of the Arrhenius equation are independent upon each other in the whole temperature range from the triple point to the critical point.