bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Characterization of IMP-1-Producing Enterobacter cloacae Complex Isolates in Tokyo
Authors: Aoki Kotaro , Harada Sohei , Yahara Koji , Ishii Yoshikazu , Motooka Daisuke , Nakamura Shota , Akeda Yukihiro , Iida Tetsuya , Tomono Kazunori , Iwata Satoshi , Moriya Kyoji , Tateda Kazuhiro 
Published: January 2018

ABSTRACT

Although KPC enzymes are most common among carbapenemases produced by
Enterobacter cloacae
complex globally, the epidemiology varies from one country to another. While previous studies have suggested that IMP enzymes are most common in Japan, detailed analysis has been scarce thus far. Here, we carried out a molecular epidemiological study and plasmid analysis of IMP-1-producing
E. cloacae
complex isolates collected from three hospitals in central Tokyo using whole-genome sequencing. Seventy-one isolates were classified into several sequence types (STs), and 49 isolates were identified as
Enterobacter hormaechei
ST78. Isolates of ST78 were divided into three clades by core-genome single nucleotide polymorphism (SNP)-based phylogenetic analysis. Whereas isolates of clade 3 were isolated from only one hospital, isolates of clade 1 and 2 were identified from multiple hospitals. Ten of 12 clade 1 isolates and 1 of 4 clade 2 isolates carried
bla
IMP-1
on IncHI2 plasmids, with high similarity of genetic structures. In addition, these plasmids shared backbone structures with IncHI2 plasmids carrying
bla
IMP
reported from other countries of the Asia-Pacific region. All isolates of clade 3 except one carried
bla
IMP-1
in In1426 on IncW plasmids. An isolate of clade 3, which lacked IncW plasmids, carried
bla
IMP-1
in In1426 on an IncFIB plasmid. These observations suggest that IMP-producing
E. cloacae
complex isolates with a diversity of host genomic backgrounds have spread in central Tokyo, and they indicate the possible contribution of IncHI2 plasmids toward this phenomenon.
Neutralizing Alpha-Toxin Accelerates Healing of Staphylococcus aureus-Infected Wounds in Nondiabetic and Diabetic Mice
Authors: Ortines Roger V. , Liu Haiyun , Cheng Lily I. , Cohen Taylor S. , Lawlor Heather , Gami Abhishek , Wang Yu , Dillen Carly A. , Archer Nathan K. , Miller Robert J. , Ashbaugh Alyssa G. , Pinsker Bret L. , Marchitto Mark C. , Tkaczyk Christine , Stover C. Kendall , Sellman Bret R. , Miller Lloyd S. 
Published: January 2018

ABSTRACT

Staphylococcus aureus
wound infections delay healing and result in invasive complications such as osteomyelitis, especially in the setting of diabetic foot ulcers. In preclinical animal models of
S. aureus
skin infection, antibody neutralization of alpha-toxin (AT), an
S. aureus
-secreted pore-forming cytolytic toxin, reduces disease severity by inhibiting skin necrosis and restoring effective host immune responses. However, whether therapeutic neutralization of alpha-toxin is effective against
S. aureus
-infected wounds is unclear. Herein, the efficacy of prophylactic treatment with a human neutralizing anti-AT monoclonal antibody (MAb) was evaluated in an
S. aureus
skin wound infection model in nondiabetic and diabetic mice. In both nondiabetic and diabetic mice, anti-AT MAb treatment decreased wound size and bacterial burden and enhanced reepithelialization and wound resolution compared to control MAb treatment. Anti-AT MAb had distinctive effects on the host immune response, including decreased neutrophil and increased monocyte and macrophage infiltrates in nondiabetic mice and decreased neutrophil extracellular traps (NETs) in diabetic mice. Similar therapeutic efficacy was achieved with an active vaccine targeting AT. Taken together, neutralization of AT had a therapeutic effect against
S. aureus
-infected wounds in both nondiabetic and diabetic mice that was associated with differential effects on the host immune response.
Differential
In Vitro
Cytokine Induction by the Species of Cryptococcus gattii Complex
Authors: Herkert Patricia F. , dos Santos Jessica C. , Hagen Ferry , Ribeiro-Dias Fatima , Queiroz-Telles Flávio , Netea Mihai G. , Meis Jacques F. , Joosten Leo A. B. 
Published: January 2018

ABSTRACT

Cryptococcal species vary in capsule and cell size, thermotolerance, geographic distribution, and affected populations.
Cryptococcus gattii sensu stricto
and
C. deuterogattii
affect mainly immunocompetent hosts; however,
C. bacillisporus
,
C. decagattii
, and
C. tetragattii
cause infections mainly in immunocompromised hosts. This study aimed to compare the capacities of different species of the
C. gattii
species complex to induce cytokines and antimicrobial molecules in human peripheral blood mononuclear cells (PBMCs).
Cryptococcus bacillisporus
and
C. deuterogattii
induced the lowest levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 among the five species of the
C. gattii
complex.
Cryptococcus deuterogattii
induced higher levels of IL-22 than those induced by
C. tetragattii
and the environmental species
C. flavescens
. In addition,
C. bacillisporus
and
C. gattii sensu stricto
proliferated inside human monocyte-derived macrophages after 24 h of infection. All
Cryptococcus
species were able to generate reactive oxygen species (ROS) in human PBMCs, with
C. bacillisporus
and
C. deuterogattii
being more efficient than the other species. In conclusion,
C. bacillisporus
and
C. deuterogattii
induce lower levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and higher ROS levels than those induced by the other species. Species of the
Cryptococcus gattii
complex have different abilities to induce cytokine and ROS production by human PBMCs.
Cyclic di-GMP Regulates TfoY in Vibrio cholerae To Control Motility by both Transcriptional and Posttranscriptional Mechanisms
Authors: Pursley Benjamin R. , Maiden Michael M. , Hsieh Meng-Lun , Fernandez Nicolas L. , Severin Geoffrey B. , Waters Christopher M. 
Published: January 2018

ABSTRACT3′,5′-Cyclic diguanylic acid (c-di-GMP) is a bacterial second messenger molecule that is a key global regulator inVibrio cholerae, but the molecular mechanisms by which this molecule regulates downstream phenotypes have not been fully characterized. One such regulatory factor that may respond to c-di-GMP is the Vc2 c-di-GMP-binding riboswitch that is hypothesized to control the expression of the downstream putative transcription factor TfoY. Although much is known about the physical and structural properties of the Vc2 riboswitch aptamer, the nature of its expression and function inV. choleraehas not been investigated. Here, we show that Vc2 functions as an off switch to inhibit TfoY production at intermediate and high concentrations of c-di-GMP. At low c-di-GMP concentrations, TfoY production is induced to stimulate dispersive motility. We also observed increased transcription oftfoYat high intracellular concentrations of c-di-GMP, but this induction is independent of the Vc2 riboswitch and occurs via transcriptional control of promoters upstream oftfoYby the previously identified c-di-GMP dependent transcription factor VpsR. Our results show that TfoY is induced by c-di-GMP at both low and high intracellular concentrations of c-di-GMP via posttranscriptional and transcriptional mechanisms, respectively. This regulation contributes to the formation of three distinct c-di-GMP signaling states inV. cholerae.IMPORTANCEThe bacterial pathogenVibrio choleraemust transition between life in aquatic environmental reservoirs and life in the gastrointestinal tract. Biofilm formation and bacterial motility, and their control by the second messenger molecule c-di-GMP, play integral roles in this adaptation. Here, we define the third major mechanism by which c-di-GMP controls bacterial motility. This pathway utilizes a noncoding RNA element known as a riboswitch that, when bound to c-di-GMP, inhibits the expression of the transcription factor TfoY. TfoY production switchesV. choleraemotility from a dense to a dispersive state. Our results suggest that the c-di-GMP signaling network ofV. choleraecan exist in at least three distinct states to regulate biofilm formation and motility.
Corynebacterium diphtheriae Iron-Regulated Surface Protein HbpA Is Involved in the Utilization of the Hemoglobin-Haptoglobin Complex as an Iron Source
Authors: Lyman Lindsey R. , Peng Eric D. , Schmitt Michael P. 
Published: January 2018

ABSTRACT

Corynebacterium diphtheriae
utilizes various heme-containing proteins, including hemoglobin (Hb) and the hemoglobin-haptoglobin complex (Hb-Hp), as iron sources during growth in iron-depleted environments. The ability to utilize Hb-Hp as an iron source requires the surface-anchored proteins HtaA and either ChtA or ChtC. The ability to bind hemin, Hb, and Hb-Hp by each of these
C. diphtheriae
proteins requires the previously characterized conserved region (CR) domain. In this study, we identified an Hb-Hp binding protein, HbpA (38.5 kDa), which is involved in the acquisition of hemin iron from Hb-Hp. HbpA was initially identified from total cell lysates as an iron-regulated protein that binds to both Hb and Hb-Hp
in situ
. HbpA does not contain a CR domain and has sequence similarity only to homologous proteins present in a limited number of
C. diphtheriae
strains. Transcription of
hbpA
is regulated in an iron-dependent manner that is mediated by DtxR, a global iron-dependent regulator. Deletion of
hbpA
from
C. diphtheriae
results in a reduced ability to utilize Hb-Hp as an iron source but has little or no effect on the ability to use Hb or hemin as an iron source. Cell fractionation studies showed that HbpA is both secreted into the culture supernatant and associated with the membrane, where its exposure on the bacterial surface allows HbpA to bind Hb and Hb-Hp. The identification and analysis of HbpA enhance our understanding of iron uptake in
C. diphtheriae
and indicate that the acquisition of hemin iron from Hb-Hp may involve a complex mechanism that requires multiple surface proteins.

IMPORTANCE
The ability to utilize host iron sources, such as heme and heme-containing proteins, is essential for many bacterial pathogens to cause disease. In this study, we have identified a novel factor (HbpA) that is crucial for the use of hemin iron from the hemoglobin-haptoglobin complex (Hb-Hp). Hb-Hp is considered one of the primary sources of iron for certain bacterial pathogens. HbpA has no similarity to the previously identified Hb-Hp binding proteins, HtaA and ChtA/C, and is found only in a limited group of
C. diphtheriae
strains. Understanding the function of HbpA may significantly increase our knowledge of how this important human pathogen can acquire host iron that allows it to survive and cause disease in the human respiratory tract.
Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus
Authors: Zhao Kuan , Gao Jia-Cong , Xiong Jun-Yao , Guo Jin-Chao , Yang Yong-Bo , Jiang Cheng-Gang , Tang Yan-Dong , Tian Zhi-Jun , Cai Xue-Hui , Tong Guang-Zhi , An Tong-Qing 
Published: January 2018

ABSTRACT

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) possesses greater replicative capacity and pathogenicity than classical PRRSV. However, the factors that lead to enhanced replication and pathogenicity remain unclear. In our study, an alignment of all available full-length sequences of North American-type PRRSVs (
n
= 204) revealed two consistent amino acid mutations that differed between HP-PRRSV and classical PRRSV and were located at positions 519 and 544 in nonstructural protein 9. Next, a series of mutant viruses with either single or double amino acid replacements were generated from HP-PRRSV HuN4 and classical PRRSV CH-1a infectious cDNA clones. Deletion of either of the amino acids led to a complete loss of virus viability. In both Marc-145 and porcine alveolar macrophages, the replicative efficiencies of mutant viruses based on HuN4 were reduced compared to the parent, whereas the replication level of CH-1a-derived mutant viruses was increased. Plaque growth assays showed clear differences between mutant and parental viruses. In infected piglets, the pathogenicity of HuN4-derived mutant viruses, assessed through clinical symptoms, viral load in sera, histopathology examination, and thymus atrophy, was reduced. Our results indicate that the amino acids at positions 519 and 544 in NSP9 are involved in the replication efficiency of HP-PRRSV and contribute to enhanced pathogenicity. This study is the first to identify specific amino acids involved in PRRSV replication or pathogenicity. These findings will contribute to understanding the molecular mechanisms of PRRSV replication and pathogenicity, leading to better therapeutic and prognostic options to combat the virus.

IMPORTANCE
Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a significant threat to the global pig industry. Highly pathogenic PRRSV (HP-PRRSV) first emerged in China in 2006 and has subsequently spread across Asia, causing considerable damage to local economies. HP-PRRSV strains possess a greater replication capacity and higher pathogenicity than classical PRRSV strains, although the mechanisms that underlie these characteristics are unclear. In the present study, we identified two mutations in HP-PRRSV strains that distinguish them from classical PRRSV strains. Further experiments that swapped the two mutations in an HP-PRRSV strain and a classical PRRSV strain demonstrated that they are involved in the replication efficiency of the virus and its virulence. Our findings have important implications for understanding the molecular mechanisms of PRRSV replication and pathogenicity and also provide new avenues of research for the study of other viruses.
Trends and correlates of the public’s perception of healthcare systems in the European Union: a multilevel analysis of Eurobarometer survey data from 2009 to 2013
Authors: AlSaud AlJohara M , Taddese Henock B , Filippidis Filippos T 
Published: January 2018

ObjectiveThe aim of the study is to assess trends in public perceptions of health systems in 27 European Union (EU) member states following the financial crisis (2009–2013), in order to discuss observed changes in the context of the financial crisis.DesignRepeated cross-sectional studies.Setting27 EU countries.ParticipantsEU citizens aged 15 years and older.MethodsThe study mainly uses the Eurobarometer Social Climate Survey, conducted annually between 2009 and 2013, thereby analysing 116 706 observations. A multilevel logistic regression was carried out to analyse trends over time and the factors associated with citizens’ perceptions of their healthcare systems.ResultsEuropeans generally exhibit positive perceptions of their national healthcare systems, 64.0% (95% CI 63.6% to 64.4%). However, we observed a significant drop in positive perceptions in the years following the crisis, especially within countries most affected by the crisis. Concerning fiscal characteristics, wealthier countries and those dedicating higher proportion of their national income to health were more likely to maintain positive perceptions. At the individual level, perceptions of healthcare systems were significantly associated with respondents’ self-perceptions of their social status, financial capacity and overall satisfaction in life.ConclusionsOur finding confirms previous observations that citizens’ perceptions of their healthcare systems may reflect their overall prospects within the broader socioeconomic systems they live in; which have in turn been affected by the financial crisis and the policy measures instituted in response.
The association between macronutrient intake and cognition in individuals aged under 65 in China: a cross-sectional study
Authors: Ding Bingjie , Xiao Rong , Ma Weiwei , Zhao Lei , Bi Yanxia , Zhang Yong 
Published: January 2018

ObjectiveThe aim of this retrospective study was to explore the correlation between daily energy intake from macronutrients and cognitive functions in a Chinese population aged less than 65 years.DesignThis is a cross-sectional study to explore the relationships between macronutrients' intake and cognitive function. The analysis of variance (ANOVA) and χ2test were used to compare the demographic and physical characteristics, lifestyle and laboratory parameters with the intake of macronutrients among different quartiles of % fat/energy. Multivariate logistic regression analysis was applied to identify the potential risk factors of mild cognitive impairment (MCI).ParticipantsYoung and middle-aged participants (age <65 years) were recruited from Beijing, China. The Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) were used to evaluate the cognitive functions, and the dietary intake of the participants was estimated with a semi-quantitative food frequency questionnaire (FFQ).ResultsAmong the 661 participants, 80 (12.1%) had MCI, while 581 (87.9%) had normal cognitive functions. On evaluating the data based on the age group, educational background, and conditions of hyperlipidaemia and total energy intake, the results revealed that high % fat (upper quartile: adjusted OR (aOR) 3.90, 95% CI1.53 to 9.89, P=0.004), and high % protein intake (upper quartile: aOR 2.77, 95% CI 1.24 to 6.15) were greatly associated with increased frequency of MCI, while high % carbohydrate intake (upper quartile: aOR0.30, 95% CI 0.12 to 0.72) was correlated with decreased prevalence of MCI.ConclusionThe dietary pattern with high percentage of energy intake from fat and protein, and low-energy intake from carbohydrate might have been associated with cognitive decline in a Chinese population under 65 years of age.
Perceptions of the uses of routine general practice data beyond individual care in England: a qualitative study
Authors: Wyatt David , Cook Jenny , McKevitt Christopher 
Published: January 2018

ObjectiveTo investigate how different lay and professional groups perceive and understand the use of routinely collected general practice patient data for research, public health, service evaluation and commissioning.Design, method, participants and settingWe conducted a multimethod, qualitative study. This entailed participant observation of the design and delivery of a series of deliberative engagement events about a local patient database made of routine primary care data. We also completed semistructured interviews with key professionals involved in the database. Qualitative data were thematically analysed. The research took place in an inner city borough in England.ResultsOf the community groups who participated in the six engagement events (111 individual citizens), five were health focused. It was difficult to recruit other types of organisations. Participants supported the uses of the database, but it was unclear how well they understood its scope and purpose. They had concerns about transparency, security and the potential misuse of data. Overall, they were more focused on the need for immediate investment in primary care capacity than data infrastructures to improve future health. The 10 interviewed professionals identified the purpose of the database in different ways, according to their interests. They emphasised the promise of the database as a resource in health research in its own right and in linking it to other datasets.ConclusionsFindings demonstrate positivity to the uses of this local database, but a disconnect between the long-term purposes of the database and participants’ short-term priorities for healthcare quality. Varying understandings of the database and the potential for it to be used in multiple different ways in the future cement a need for systematic and routine public engagement to develop and maintain public awareness. Problems recruiting community groups signal a need to consider how we engage wider audiences more effectively.
Task errors by emergency physicians are associated with interruptions, multitasking, fatigue and working memory capacity: a prospective, direct observation study
Authors: Westbrook Johanna I , Raban Magdalena Z , Walter Scott R , Douglas Heather 
Published: January 2018

BackgroundInterruptions and multitasking have been demonstrated in experimental studies to reduce individuals’ task performance. These behaviours are frequently used by clinicians in high-workload, dynamic clinical environments, yet their effects have rarely been studied.ObjectiveTo assess the relative contributions of interruptions and multitasking by emergency physicians to prescribing errors.Methods36 emergency physicians were shadowed over 120 hours. All tasks, interruptions and instances of multitasking were recorded. Physicians’ working memory capacity (WMC) and preference for multitasking were assessed using the Operation Span Task (OSPAN) and Inventory of Polychronic Values. Following observation, physicians were asked about their sleep in the previous 24 hours. Prescribing errors were used as a measure of task performance. We performed multivariate analysis of prescribing error rates to determine associations with interruptions and multitasking, also considering physician seniority, age, psychometric measures, workload and sleep.ResultsPhysicians experienced 7.9 interruptions/hour. 28 clinicians were observed prescribing 239 medication orders which contained 208 prescribing errors. While prescribing, clinicians were interrupted 9.4 times/hour. Error rates increased significantly if physicians were interrupted (rate ratio (RR) 2.82; 95% CI 1.23 to 6.49) or multitasked (RR 1.86; 95% CI 1.35 to 2.56) while prescribing. Having below-average sleep showed a >15-fold increase in clinical error rate (RR 16.44; 95% CI 4.84 to 55.81). WMC was protective against errors; for every 10-point increase on the 75-point OSPAN, a 19% decrease in prescribing errors was observed. There was no effect of polychronicity, workload, physician gender or above-average sleep on error rates.ConclusionInterruptions, multitasking and poor sleep were associated with significantly increased rates of prescribing errors among emergency physicians. WMC mitigated the negative influence of these factors to an extent. These results confirm experimental findings in other fields and raise questions about the acceptability of the high rates of multitasking and interruption in clinical environments.