bluuebunny/crossref_metadata_2025_split huggingface dataset:
The CpxRA Two-Component System Is Essential for Citrobacter rodentium Virulence
Authors: Thomassin Jenny-Lee , Giannakopoulou Natalia , Zhu Lei , Gross Jeremy , Salmon Kristiana , Leclerc Jean-Mathieu , Daigle France , Le Moual Hervé , Gruenheid Samantha 
Published: February 2015

ABSTRACT

Citrobacter rodentium
is a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagic
Escherichia coli
and enteropathogenic
E. coli
. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. In
E. coli
, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed that
cpxRA
was expressed in the colon of C57BL/6J mice infected with
C. rodentium
. To determine whether CpxRA plays a role during
C. rodentium
infection, a
cpxRA
deletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation of
cpxRA
restored virulence. The
C. rodentium
strains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the Δ
cpxRA
strain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that the
cpxRA
expression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for the
in vivo
virulence of
C. rodentium
. In addition, these data suggest that fine-tuned
cpxRA
expression is important for infection. This is the first study that identifies a
C. rodentium
two-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens.
Complete Biosynthetic Pathway of the C50Carotenoid Bacterioruberin from Lycopene in the Extremely Halophilic Archaeon Haloarcula japonica
Authors: Yang Ying , Yatsunami Rie , Ando Ai , Miyoko Nobuhiro , Fukui Toshiaki , Takaichi Shinichi , Nakamura Satoshi 
Published: February 2015

ABSTRACTHaloarcula japonica, an extremely halophilic archaeon that requires high concentrations of NaCl for growth, accumulates the C50carotenoid bacterioruberin (BR). By homology analysis, a gene cluster, includingc0507,c0506, andc0505, was found and predicted to be involved in the synthesis of bacterioruberin. To elucidate the function of the encoded enzymes, we constructedHa. japonicamutants of these genes and analyzed carotenoids produced by the mutants. Our research showed thatc0507,c0506, andc0505encoded a carotenoid 3,4-desaturase (CrtD), a bifunctional lycopene elongase and 1,2-hydratase (LyeJ), and a C50carotenoid 2″,3″-hydratase (CruF), respectively. The above three carotenoid biosynthetic enzymes catalyze the reactions that convert lycopene to bacterioruberin inHa. japonica. This is the first identification of functional CrtD and CruF in archaea and elucidation of the complete biosynthetic pathway of bacterioruberin from lycopene.IMPORTANCEHaloarcula japonica, an extremely halophilic archaeon, accumulates the C50carotenoid bacterioruberin (BR). In this study, we have identified three BR biosynthetic enzymes and have elucidated their functions. Among them, two enzymes were found in an archaeon for the first time. Our results revealed the biosynthetic pathway responsible for production of BR inHa. japonicaand provide a basis for investigating carotenoid biosynthetic pathways in other extremely halophilic archaea. Elucidation of the carotenoid biosynthetic pathway inHa. japonicamay also prove useful for producing the C50carotenoid BR efficiently by employing genetically modified haloarchaeal strains.
The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance
Authors: Kreamer Naomi N. , Costa Flavia , Newman Dianne K. 
Published: February 2015

ABSTRACT

The physiological resistance of pathogens to antimicrobial treatment is a severe problem in the context of chronic infections. For example, the mucus-filled lungs of cystic fibrosis (CF) patients are readily colonized by diverse antibiotic-resistant microorganisms, including
Pseudomonas aeruginosa
. Previously, we showed that bioavailable ferrous iron [Fe(II)] is present in CF sputum at all stages of infection and constitutes a significant portion of the iron pool at advanced stages of lung function decline [R. C. Hunter et al., mBio 4(4):e00557-13, 2013].
P. aeruginosa
, a dominant CF pathogen, senses Fe(II) using a two-component signal transduction system, BqsRS, which is transcriptionally active in CF sputum [R. C. Hunter et al., mBio 4(4):e00557-13, 2013; N. N. Kreamer, J. C. Wilks, J. J. Marlow, M. L. Coleman, and D. K. Newman, J Bacteriol 194:1195–1204, 2012]. Here, we show that an RExxE motif in BqsS is required for BqsRS activation. Once Fe(II) is sensed, BqsR binds a tandem repeat DNA sequence, activating transcription. The BqsR regulon—defined through iterative bioinformatic predictions and experimental validation—includes several genes whose products are known to drive antibiotic resistance to aminoglycosides and polymyxins. Among them are genes encoding predicted determinants of polyamine transport and biosynthesis. Compared to the wild type,
bqsS
and
bqsR
deletion mutants are sensitive to high levels of Fe(II), produce less spermidine in high Fe(II), and are more sensitive to tobramycin and polymyxin B but not arsenate, chromate, or cefsulodin. BqsRS thus mediates a physiological response to Fe(II) that guards the cell against positively charged molecules but not negatively charged stressors. These results suggest Fe(II) is an important environmental signal that, via BqsRS, bolsters tolerance of a variety of cationic stressors, including clinically important antimicrobial agents.

IMPORTANCE
Clearing chronic infections is challenging due to the physiological resistance of opportunistic pathogens to antibiotics. Effective treatments are hindered by a lack of understanding of how these organisms survive
in situ
. Fe(II) is typically present at micromolar levels in soils and sedimentary habitats, as well as in CF sputum. All P. aeruginosa strains possess a two-component system, BqsRS, that specifically senses extracellular Fe(II) at low micromolar concentrations. Our work shows that BqsRS protects the cell against cationic perturbations to the cell envelope as well as low pH and reduction potential (Eh), conditions under which Fe
2+
is stable. Fe(II) can thus be understood as a proxy for a broader environmental state; the cellular response to its detection may help rationalize the resistance of P. aeruginosa to clinically important cationic antibiotics. This finding demonstrates the importance of considering environmental chemistry when exploring mechanisms of microbial survival in habitats that include the human body.
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes
Authors: Vu Bao G. , Stach Christopher S. , Kulhankova Katarina , Salgado-Pabón Wilmara , Klingelhutz Aloysius J. , Schlievert Patrick M. 
Published: February 2015

ABSTRACT

Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of
Staphylococcus aureus
colonization and overt infections.
S. aureus
causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among
S. aureus
virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to
S. aureus
superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to
S. aureus
superantigens facilitates the development of DMII, which may lead to therapeutic targeting of
S. aureus
and its superantigens.

IMPORTANCE
Obesity has a strong correlation with type 2 diabetes, in which fatty tissue, containing adipocytes, contributes to the development of the illness through altered metabolism and chronic inflammation. The human microbiome changes in persons with obesity and type 2 diabetes, including increases in
Staphylococcus aureus
colonization and overt infections. While the microbiome is essential for human wellness, there is little understanding of the role of microbes in obesity or the development of diabetes. Here, we demonstrate that the
S. aureus
superantigen toxic shock syndrome toxin-1 (TSST-1), an essential exotoxin in pathogenesis, induces inflammation, lipolysis, and insulin resistance in adipocytes both
in vitro
and
in vivo
. Chronic stimulation of rabbits with TSST-1 results in impaired systemic glucose tolerance, the hallmark finding in type 2 diabetes in humans, suggesting a role of
S. aureus
and its superantigens in the progression to type 2 diabetes.
Provider beliefs about diabetes treatment have little impact on glycemic control of their patients with diabetes
Authors: LeBlanc Erin S , Rosales A Gabriela , Kachroo Sumesh , Mukherjee Jayanti , Funk Kristine L , Schneider Jennifer L , Nichols Gregory A 
Published: February 2015

ObjectiveTo improve the health of people with diabetes, it is essential to identify why patients experience extended periods of poor glycemic control before therapeutic intensification.Research design and methodsWe surveyed 252 primary care providers at Kaiser Permanente Northwest to determine their beliefs about the glycemic goals of their patients, treatment intensification behavior, and barriers to achieving optimal glycemic control. We linked the responses of 149 providers to the health records of their 18 346 patients with diabetes.ResultsPatient glycemic levels were not related to either individualized glycemic goals or provider intensification behavior. Providers’ beliefs about diabetic treatment and glycated hemoglobin (HbA1c) goals were poorly associated with patient HbA1c levels. Providers identified patients’ resistance to lifestyle behaviors and taking insulin, lack of medication adherence, and psychosocial issues as the main barriers to optimal glycemic control. Lack of time to care for complex patients was also a barrier. Providers who agreed that “current research did not support A1C levels <7%” were less likely to have patients with HbA1c levels <7% (OR=0.87, 95% CI 0.78 to 0.97) and patients of providers who disagreed that “some patients will have an A1C >9% no matter what I do” were 16% more likely to have patients with HbA1c <7% (1.16, 1.03 to 1.30) compared with providers who were neutral about those statements.ConclusionsGiven the consistency of HbA1c levels across providers despite differences in beliefs and intensification behaviors, these barriers may be best addressed by instituting changes at the system level (ie, instituting institutional glycemic targets or outreach for dysglycemia) rather than targeting practice patterns of individual providers.
Mental illness, poverty and stigma in India: a case–control study
Authors: Trani Jean-Francois , Bakhshi Parul , Kuhlberg Jill , Narayanan Sreelatha S , Venkataraman Hemalatha , Mishra Nagendra N , Groce Nora E , Jadhav Sushrut , Deshpande Smita 
Published: February 2015

ObjectiveTo assess the effect of experienced stigma on depth of multidimensional poverty of persons with severe mental illness (PSMI) in Delhi, India, controlling for gender, age and caste.DesignMatching case (hospital)–control (population) study.SettingUniversity Hospital (cases) and National Capital Region (controls), India.ParticipantsA case–control study was conducted from November 2011 to June 2012. 647 cases diagnosed with schizophrenia or affective disorders were recruited and 647 individuals of same age, sex and location of residence were matched as controls at a ratio of 1:2:1. Individuals who refused consent or provided incomplete interview were excluded.Main outcome measuresHigher risk of poverty due to stigma among PSMI.Results38.5% of PSMI compared with 22.2% of controls were found poor on six dimensions or more. The difference in multidimensional poverty index was 69% between groups with employment and income of the main contributors. Multidimensional poverty was strongly associated with stigma (OR 2.60, 95% CI 1.27 to 5.31), scheduled castes/scheduled tribes/other backward castes (2.39, 1.39 to 4.08), mental illness (2.07, 1.25 to 3.41) and female gender (1.87, 1.36 to 2.58). A significant interaction between stigma, mental illness and gender or caste indicates female PSMI or PSMI from ‘lower castes’ were more likely to be poor due to stigma than male controls (p<0.001) or controls from other castes (p<0.001).ConclusionsPublic stigma and multidimensional poverty linked to SMI are pervasive and intertwined. In particular for low caste and women, it is a strong predictor of poverty. Exclusion from employment linked to negative attitudes and lack of income are the highest contributors to multidimensional poverty, increasing the burden for the family. Mental health professionals need to be aware of and address these issues.
Association between C reactive protein level and depressive symptoms in an elderly Korean population: Korean Social Life, Health and Aging Project
Authors: Song Bo Mi , Lee Ju-Mi , Choi Wungrak , Youm Yoosik , Chu Sang Hui , Park Yeong-Ran , Kim Hyeon Chang 
Published: February 2015

ObjectiveThe relationship between inflammatory markers and depressive symptoms has been reported inconsistently. Moreover, there were only a few studies conducted in an Asian population. The purpose of this study was to examine the association between C reactive protein (CRP) and depressive symptoms in an elderly Korean population.Design, setting and participantsThis study used data from the Korean Social Life, Health and Aging Project Health Examination Cohort, which started in 2011. Among participants aged 60 or over recruited from a rural community, 569 (224 men and 345 women) without a history of stroke, angina pectoris, myocardial infarction or CRP≥20 mg/L were employed for cross-sectional analyses. As a marker of systemic inflammation, CRP was measured. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple linear regression analysis was used to investigate the relationship between CRP and depressive symptoms.ResultsIn men, CRP levels had significant associations with depressive symptoms before (β=0.420, p=0.010) and after (β=0.336, p=0.025) adjusting for age, body mass index, systolic blood pressure, number of comorbidities, smoking status, alcohol intake, marital status, education and sleep duration. However, in women, the association between CRP and depressive symptoms was not significant before (p=0.250) and after (p=0.256) adjustment.ConclusionsOur findings suggest that elevated CRP levels are independently associated with the presence of depressive symptoms in elderly Korean men.
What do external consultants from private and not-for-profit companies offer healthcare commissioners? A qualitative study of knowledge exchange
Authors: Wye Lesley , Brangan Emer , Cameron Ailsa , Gabbay John , Klein Jonathan H , Anthwal Rachel , Pope Catherine 
Published: February 2015

ObjectivesThe use of external consultants from private and not-for-profit providers in the National Health Service (NHS) is intended to improve the quality of commissioning. The aim of this study was to learn about the support offered to healthcare commissioners, how external consultants and their clients work together and the perceived impact on the quality of commissioning.SettingNHS commissioning organisations and private and not-for-profit providers.DesignMixed methods case study of eight cases.Data collection92 interviews with external consultants (n=36), their clients (n=47) and others (n=9). Observation of 25 training events and meetings. Documentation, for example, meeting minutes and reports.AnalysisConstant comparison. Data were coded, summarised and analysed by the research team with a coding framework to facilitate cross-case comparison.ResultsIn the four contracts presented here, external providers offered technical solutions (eg, software tools), outsourcing and expertise including project management, data interpretation and brokering relationships with experts. In assessing perceived impact on quality of commissioning, two contracts had limited value, one had short-term benefits and one provided short and longer term benefits. Contracts with commissioners actively learning, embedding and applying new skills were more valued. Other elements of success were: (1) addressing clearly agreed problems of relevance to managerialandoperational staff (2) solutions co-produced at all organisational levels (3) external consultants working directly with clients to interpret data outputs to inform locally contextualised commissioning strategies. Without explicit knowledge exchange strategies, outsourcing commissioning to external providers resulted in the NHS clients becoming dependent.ConclusionsNHS commissioning will be disadvantaged if commissioners both fail to learn in the short term from the knowledge of external providers and in the longer term lose local skills. Knowledge exchange mechanisms are a vital component of commissioning and should be embedded in external provider contracts.
Large regional differences in incidence of arthroscopic meniscal procedures in the public and private sector in Denmark
Authors: Hare Kristoffer Borbjerg , Vinther Jesper Høeg , Lohmander L Stefan , Thorlund Jonas Bloch 
Published: February 2015

ObjectivesA recent study reported a large increase in the number of meniscal procedures from 2000 to 2011 in Denmark. We examined the nation-wide distribution of meniscal procedures performed in the private and public sector in Denmark since different incentives may be present and the use of these procedures may differ from region to region.SettingWe included data on all patients who underwent an arthroscopic meniscal procedure performed in the public or private sector in Denmark.ParticipantsData were retrieved from the Danish National Patient Register on patients who underwent arthroscopic meniscus surgery as a primary or secondary procedure in the years 2000 to 2011. Hospital identification codes enabled linkage of performed procedures to specific hospitals.Primary and secondary outcome measuresYearly incidence of meniscal procedures per 100 000 inhabitants was calculated with 95% CIs for public and private procedures for each region.ResultsIncidence of meniscal procedures increased at private and at public hospitals. The private sector accounted for the largest relative and absolute increase, rising from an incidence of 1 in 2000 to 98 in 2011. In 2011, the incidence of meniscal procedures was three times higher in the Capital Region than in Region Zealand.ConclusionsOur study identified a large increase in the use of meniscal procedures in the public and private sector in Denmark. The increase was particularly conspicuous in the private sector as its proportion of procedures performed increased from 1% to 32%. Substantial regional differences were present in the incidence and trend over time of meniscal procedures.
‘Do Well B.’: Design Of WELL Being monitoring systems. A study protocol for the application in autism
Authors: Dutheil Frédéric , Chambres Patrick , Hufnagel Cédric , Auxiette Catherine , Chausse Pierre , Ghozi Raja , Paugam Guillaume , Boudet Gil , Khalfa Nadia , Naughton Geraldine , Chamoux Alain , Mermillod Martial , Bertrand Pierre Raphael 
Published: February 2015

IntroductionIndividuals with autism spectrum disorder (ASD) have difficulties in communication and social interaction resulting from atypical perceptual and cognitive information processing, leading to an accumulation of anxiety. Extreme overloading experienced internally may not be externally visible. Identifying stressful situations at an early stage may avoid socially problematic behaviour from occurring, such as self-injurious behaviour. Activation of the autonomous nervous system (ANS) is involved in the response to anxiety, which can be measured through heart rate variability and skin conductance with the use of portable devices, non-intrusively and pain-free. Thus, developing innovative analysis of signal perception and reaction is necessary, mainly for non-communicative individuals with autism.Methods and analysisThe protocol will take place in real life (home and social environments). We aim to associate modifications of the ANS with external events that will be recorded in a synchronous manner through a specific design (spy glasses with video/audio recording). Four phases will be carried out on ASD participants and aged-matched controls: (1) 24-hour baseline pre-experiment (physical activity, sleep), (2) 2 h in a real life situation, (3) 30 min in a quiet environment, interrupted by a few seconds of stressful sound, (4) an interview to record feelings about events triggering anxiety. ASD and control participants will be together for phases 2 and 3, revealing different physiological responses to the same situations, and thus identifying potentially problematic events. The novelty will be to apply time-series analyses (which led to several Nobel Prizes in quantitative finance) on ANS series (heart rate, heart rate variability, skin conductance) and wrist motion.Ethics and disseminationEthical approval has been obtained from Ethics Committee of Clermont-Ferrand (South-East I), France (2014-A00611–46). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures and our websites.Trial registration numberClinicalTrials identifierNCT02275455.
Patients’ practices and experiences of using nebuliser therapy in the management of COPD at home
Authors: Alhaddad B , Smith F J , Robertson T , Watman G , Taylor K M G 
Published: February 2015

Background and aimHow patients use their nebulisers at home is vital to ensure effective treatment and optimal health outcomes for patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to identify the practicalities and problems associated with nebuliser use by patients with COPD at home, which may impact on the safety and effectiveness of therapy.Design and settingA cross-sectional descriptive study in which participants were recruited from two levels of care: primary care, involving 38 GP practices in North West London, and intermediate care with a major acute hospital.MethodIn-depth interviews were conducted with a representative sample of 50 patients with COPD using nebulisers in their home, recruited from general practice populations and at hospital discharge. A checklist was used to record activities and patients demonstrated use of their nebuliser. Qualitative procedures were employed to identify the range of problems experienced with nebuliser use.ResultsA wide range of practical issues was identified at all stages: problems prior to nebulisation: setting up equipment, lack of instructions, manual dexterity and time required. Problems during medication administration: inhalation technique, duration of nebulisation and understanding how to achieve optimal efficacy. Problems post-administration: inadequate cleaning of nebuliser components, access to accessories and use of damaged parts or self-repairs. Other problems included noise, weight and non-portability of equipment.ConclusionsPatients with COPD using nebulisers at home experienced problems with all aspects, many of which may be anticipated to compromise clinical outcomes. Healthcare providers should be aware of these problems to effectively support patients with COPD with the use of their nebulisers at home.