bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Rhomboid Protease GlpG Promotes the Persistence of Extraintestinal Pathogenic Escherichia coli within the Gut
Authors: Russell Colin W. , Richards Amanda C. , Chang Alexander S. , Mulvey Matthew A. 
Published: April 2017

ABSTRACT

Extraintestinal pathogenic
Escherichia coli
(ExPEC) strains are typically benign within the mammalian gut but can disperse to extraintestinal sites to cause diseases like urinary tract infections and sepsis. As occupation of the intestinal tract is often a prerequisite for ExPEC-mediated pathogenesis, we set out to understand how ExPEC colonizes this niche. A screen using transposon sequencing (Tn-seq) was performed to search for genes within ExPEC isolate F11 that are important for growth in intestinal mucus, which is thought to be a major source of nutrients for
E. coli
in the gut. Multiple genes that contribute to ExPEC fitness in mucus broth were identified, with genes that are directly or indirectly associated with fatty acid beta-oxidation pathways being especially important. One of the identified mucus-specific fitness genes encodes the rhomboid protease GlpG.
In vitro
, we found that the disruption of
glpG
had polar effects on the downstream gene
glpR
, which encodes a transcriptional repressor of factors that catalyze glycerol degradation. Mutation of either
glpG
or
glpR
impaired ExPEC growth in mucus and on plates containing the long-chain fatty acid oleate as the sole carbon source. In contrast, in a mouse gut colonization model in which the natural microbiota is unperturbed, the disruption of
glpG
but not
glpR
significantly reduced ExPEC survival. This work reveals a novel biological role for a rhomboid protease and highlights new avenues for defining mechanisms by which ExPEC strains colonize the mammalian gastrointestinal tract.
Suppressors of dGTP Starvation in Escherichia coli
Authors: Itsko Mark , Schaaper Roel M. 
Published: April 2017

ABSTRACT

dGTP starvation, a newly discovered phenomenon in which
Escherichia coli
cells are starved specifically for the DNA precursor dGTP, leads to impaired growth and, ultimately, cell death. Phenomenologically, it represents an example of nutritionally induced unbalanced growth: cell mass amplifies normally as dictated by the nutritional status of the medium, but DNA content growth is specifically impaired. The other known example of such a condition, thymineless death (TLD), involves starvation for the DNA precursor dTTP, which has been found to have important chemotherapeutic applications. Experimentally, dGTP starvation is induced by depriving an
E. coli
gpt optA1
strain of its required purine source, hypoxanthine. In our studies of this phenomenon, we noted the emergence of a relatively high frequency of suppressor mutants that proved resistant to the treatment. To study such suppressors, we used next-generation sequencing on a collection of independently obtained mutants. A significant fraction was found to carry a defect in the PurR transcriptional repressor, controlling
de novo
purine biosynthesis, or in its downstream
purEK
operon. Thus, upregulation of
de novo
purine biosynthesis appears to be a major mode of overcoming the lethal effects of dGTP starvation. In addition, another large fraction of the suppressors contained a large tandem duplication of a 250- to 300-kb genomic region that included the
purEK
operon as well as the
acrAB
-encoded multidrug efflux system. Thus, the suppressive effects of the duplications could potentially involve beneficial effects of a number of genes/operons within the amplified regions.

IMPORTANCE
Concentrations of the four precursors for DNA synthesis (2′-deoxynucleoside-5′-triphosphates [dNTPs]) are critical for both the speed of DNA replication and its accuracy. Previously, we investigated consequences of dGTP starvation, where the DNA precursor dGTP was specifically reduced to a low level. Under this condition,
E. coli
cells continued cell growth but eventually developed a DNA replication defect, leading to cell death due to formation of unresolvable DNA structures. Nevertheless, dGTP-starved cultures eventually resumed growth due to the appearance of resistant mutants. Here, we used whole-genome DNA sequencing to identify the responsible suppressor mutations. We show that the majority of suppressors can circumvent death by upregulating purine
de novo
biosynthesis, leading to restoration of dGTP to acceptable levels.
Do influenza and pneumococcal vaccines prevent community-acquired respiratory infections among older people with diabetes and does this vary by chronic kidney disease? A cohort study using electronic health records
Authors: McDonald Helen I , Thomas Sara L , Millett Elizabeth R C , Quint Jennifer , Nitsch Dorothea 
Published: April 2017

ObjectiveWe aimed to estimate the effectiveness of influenza and 23-valent pneumococcal polysaccharide vaccination on reducing the burden of community-acquired lower respiratory tract infection (LRTI) among older people with diabetes, and whether this varied by chronic kidney disease (CKD) status.Research design and methodsWe used linked UK electronic health records for a retrospective cohort study of 190 492 patients ≥65 years with diabetes mellitus and no history of renal replacement therapy, 1997–2011. We included community-acquired LRTIs managed in primary or secondary care. Infection incidence rate ratios were estimated using the Poisson regression. Pneumococcal vaccine effectiveness (VE) was calculated as (1−effect measure). To estimate influenza VE, a ratio-of-ratios analysis (winter effectiveness/summer effectiveness) was used to address confounding by indication. Final VE estimates were stratified according to estimated glomerular filtration rate and proteinuria status.ResultsNeither influenza nor pneumococcal vaccine uptake varied according to CKD status. Pneumococcal VE was 22% (95% CI 11% to 31%) against community-acquired pneumonia for the first year after vaccination, but was negligible after 5 years. In the ratio-of-ratios analysis, current influenza vaccination had 7% effectiveness for preventing community-acquired LRTI (95% CI 3 to 12). Pneumococcal VE was lower among patients with a history of proteinuria than among patients without proteinuria (p=0.04), but otherwise this study did not identify variation in pneumococcal or influenza VE by markers of CKD.ConclusionsThe public health benefits of influenza vaccine may be modest among older people with diabetes. Pneumococcal vaccination protection against community-acquired pneumonia declines swiftly: alternative vaccination schedules should be investigated.
Economic study of the value of expanding HCV treatment capacity in Germany
Authors: Sbarigia Urbano , Wirth Daniel , Van Nuys Karen , Huber Caroline , Brookmeyer Ron , Stahmeyer Jona , Krauth Christian 
Published: April 2017

BackgroundToday's highly efficacious, low-toxicity interferon-free treatment regimens for chronic hepatitis C virus (HCV) can cure most patients with HCV in 12–24 weeks. The aim of this study was to understand how the introduction of shorter duration treatment regimens for HCV will impact the capacity for treatment and value to society.MethodsA Markov model of HCV transmission and progression was constructed, incorporating nationally representative data on HCV prevalence, incidence and progression; mortality, treatment costs, medical expenditures, employment probabilities and disability payments in Germany. The model was stratified by HCV genotype and exposure route (1-time healthcare exposure, injection drug use and sexual activity). Treatment scenarios were based on German treatment guidelines and projected treatment capacity. The impact of different treatment scenarios on disease transmission and prevalence, quality-adjusted life years (QALYs), treatment costs, medical expenditures, employment and disability expenditures was calculated.ResultsDepending on their adoption profile, new treatment regimens and protocols introduced over the next several years will increase HCV treatment capacity in Germany by 8–30%, reducing disease transmission and prevalence, increasing QALYs and adding €94–310 million in discounted social value (QALYs plus medical savings net of treatment costs) over a 30-year horizon. Additional social value in the form of higher employment and lower disability would also result.ConclusionsThe introduction of shorter HCV treatment regimens and the resulting increased treatment capacity in Germany would result in large gains to society by reducing disease transmission and prevalence, resulting in longer, healthier, more productive lives for current and future generations.
Cute as candy: a qualitative study of perceptions of snus branding and package design among youth in Norway
Authors: Scheffels Janne , Lund Ingeborg 
Published: April 2017

ObjectivesSnus use has increased among youth in Norway in recent years and is now more prevalent than smoking. Concurrently, a range of new products and package designs have been introduced to the market. The aim of this study was to explore how youth perceive snus branding and package design, and the role, if any, of snus packaging on perceptions of appeal and harm of snus among youth.ParticipantsAdolescent tobacco users and non-users (N=35) ages 15–17 years.DesignWe conducted interviews among 6 focus groups (each with 4–7 participants). Participants were shown snus packages with a variety of designs and with different product qualities (flavour additives, slim, regular, white and brown sachets) and group discussions focused on how they perceived packages and products. The focus group discussions were semistructured using a standard guide, and analysed thematically.ResultsThe participants in the focus groups narrated distinct images of snus brands and associated user identities. Package design elements such as shapes, colours, images and fonts were described as guiding these perceptions. Packaging elements and flavour additives were associated with perceptions of product harm. The appeal of flavoured snus products and new types of snus sachets seemed to blend in with these processes, reinforcing positive attitudes and contributing to the creation of particular identities for products and their users.ConclusionsThe findings indicate that packaging is vital to consumer's identification with, and differentiation between, snus brands. In view of this, snus branding and packaging can be seen as fulfilling a similar promotional role as advertising messages: generating preferences and appeal.
Standards for Reporting Implementation Studies (StaRI): explanation and elaboration document
Authors: Pinnock Hilary , Barwick Melanie , Carpenter Christopher R , Eldridge Sandra , Grandes Gonzalo , Griffiths Chris J , Rycroft-Malone Jo , Meissner Paul , Murray Elizabeth , Patel Anita , Sheikh Aziz , Taylor Stephanie J C 
Published: April 2017

ObjectivesImplementation studies are often poorly reported and indexed, reducing their potential to inform the provision of healthcare services. The Standards for Reporting Implementation Studies (StaRI) initiative aims to develop guidelines for transparent and accurate reporting of implementation studies.MethodsAn international working group developed the StaRI guideline informed by a systematic literature review and e-Delphi prioritisation exercise. Following a face-to-face meeting, the checklist was developed iteratively by email discussion and critical review by international experts.ResultsThe 27 items of the checklist are applicable to the broad range of study designs employed in implementation science. A key concept is the dual strands, represented as 2 columns in the checklist, describing, on the one hand, the implementation strategy and, on the other, the clinical, healthcare or public health intervention being implemented. This explanation and elaboration document details each of the items, explains the rationale and provides examples of good reporting practice.ConclusionsPreviously published reporting statements have been instrumental in improving reporting standards; adoption by journals and authors may achieve a similar improvement in the reporting of implementation strategies that will facilitate translation of effective interventions into routine practice.
Associations of moderate-to-vigorous-intensity physical activity and body mass index with glycated haemoglobin within the general population: a cross-sectional analysis of the 2008 Health Survey for England
Authors: Bakrania Kishan , Yates Thomas , Edwardson Charlotte L , Bodicoat Danielle H , Esliger Dale W , Gill Jason M R , Kazi Aadil , Velayudhan Latha , Sinclair Alan J , Sattar Naveed , Biddle Stuart J H , Hamer Mark , Davies Melanie J , Khunti Kamlesh 
Published: April 2017

ObjectivesTo investigate the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and body mass index (BMI) with glycated haemoglobin (HbA1c) in a national sample of English adults.MethodsThe 2008 Health Survey for England data were used with 1109 participants aged ≥18 providing complete data. MVPA time was assessed using an accelerometer. Weighted linear regression models, adjusted for several confounders, quantified the associations between continuous measures of MVPA and BMI with HbA1c. Interaction analyses were implemented to observe whether the association of MVPA with HbA1c was modified by BMI or vice versa. Further weighted linear regression models examined the differences in HbA1c across four mutually exclusive categories of MVPA and BMI: (1) ‘physically active and non-obese’, (2) ‘physically active and obese’, (3) ‘physically inactive and non-obese’ and (4) ‘physically inactive and obese’. ‘Physically active’ was defined as: ≥150 min/week of MVPA. ‘Obese’ was defined as: BMI ≥30.0 kg/m2. A wide range of sensitivity analyses were also implemented.ResultsEvery 30 min/day increment in MVPA was associated with a 0.7 mmol/mol (0.07% (p<0.001)) lower HbA1c level. Each 1 kg/m2increment in BMI was associated with a 0.2 mmol/mol (0.02% (p<0.001)) higher HbA1c level. The association of MVPA with HbA1c was stronger in obese individuals (−1.5 mmol/mol (−0.13% (p<0.001))) than non-obese individuals (−0.7 mmol/mol (−0.06% (p<0.001))); p=0.004 for interaction. The association of BMI with HbA1c remained stable across MVPA categories. Compared with individuals categorised as ‘physically inactive and obese’, only those categorised as ‘physically active and obese’ or ‘physically active and non-obese’ had lower HbA1c levels by 2.1 mmol/mol (0.19% (p=0.005)) and 3.5 mmol/mol (0.32% (p<0.001)), respectively. Sensitivity analyses indicated robustness and stability.ConclusionsThis study emphasises the importance of physical activity as a determinant of HbA1c, and suggests that the associations may be stronger in obese adults.
Prevalence and influencing factors of hepatitis B among a rural residential population in Zhejiang Province, China: a cross-sectional study
Authors: Yang Shigui , Ding Cheng , Cui Yuanxia , Wu Jie , Yu Chengbo , Chen Ping , Xu Kaijin , Deng Min , Li Yiping , Liu Juanjuan , Yin Pei , Ren Wen , Qiu Yan , Cao Qing , Zhou Yuqing , Yao Jun , Ruan Bing , Ren Jingjing , Li Lanjuan 
Published: April 2017

ObjectivesTo reveal the prevalence and associated influencing factors of hepatitis B among a rural residential population in Zhejiang, China, in order to help develop specific control strategies.MethodsWe conducted a cross-sectional study among a rural residential population in Zhejiang, China. Stratified multistage cluster sampling was utilised in five districts; a structured questionnaire was used to collect the information such as age, gender, education, occupation, living status, and other health related information of the participants by trained local staff; and the hepatitis B virus (HBV) infection status of the participants was determined by the chemiluminescence immunoassay test. Univariate and multivariate analyses were applied to evaluate the influencing factors of HBV infection. The odds ratio of each related factor was assessed with or without adjustment separately.ResultsThe mean age of the 16 601 participants (7881 males and 8720 females) who completed the survey was 40.28±19.47 years. The positive rate of hepatitis B surface antigen (HBsAg) was 4.04% (95% CI 3.74% to 4.35%), and 3.85% when standardised by age and gender. Univariate analysis showed that age, educational level, occupation, living status, history of hepatitis B examinations, history of blood transfusion, vaccination, family history, coastal living, and district were the potential influencing factors. Multivariate logistic regression indicated that occupation, living status, history of hepatitis B examinations, vaccination and district were the influencing factors. Undertaking a service-based tertiary industry job (ORa1.19, 95% CI 0.94 to 1.51) and non-single living (ORa2.84, 95% CI 2.17 to 3.70) might be risk factors, while vaccination (ORa0.43, 95% CI 0.34 to 0.53) and history of hepatitis B examinations (ORa0.71, 95% CI 0.48 to 1.03) were potential protective factors.ConclusionsThe prevalence of hepatitis B is at an intermediate epidemic level in a rural residential population in Zhejiang, China. Raising vaccination coverage, especially in adults, is a suitable strategy for the prevention and control of hepatitis B.
EUropean prospective cohort study onEnterobacteriaceaeshowing REsistance to CArbapenems (EURECA): a protocol of a European multicentre observational study
Authors: Gutiérrez-Gutiérrez Belén , Sojo-Dorado Jesús , Bravo-Ferrer José , Cuperus Nienke , de Kraker Marlieke , Kostyanev Tomislav , Raka Lul , Daikos George , Feifel Jan , Folgori Laura , Pascual Alvaro , Goossens Herman , O'Brien Seamus , Bonten Marc J M , Rodríguez-Baño Jesús 
Published: April 2017

IntroductionThe rapid worldwide spread of carbapenem-resistantEnterobacteriaceae(CRE) constitutes a major challenge. The aim of the EUropean prospective cohort study onEnterobacteriaceaeshowing REsistance to CArbapenems (EURECA), which is part of the Innovative Medicines Initiative Joint Undertaking (IMI JU) funded COMBACTE-CARE project, is to investigate risk factors for and outcome determinants of CRE infections to inform randomised clinical trial designs and to provide a historical cohort that could eventually be used for future comparisons with new drugs targeting CRE.MethodsA multicentre (50 sites), multinational (11 European countries), analytical observational project was designed, comprising 3 studies. The aims of study 1 (a prospective cohort study) include characterising the features, clinical management and outcomes of hospitalised patients with intra-abdominal infection, pneumonia, complicated urinary tract infections and bloodstream infections caused by CRE (202 patients in each group). The main outcomes will be 30-day all-cause mortality and clinical response. Study 2 (a nested case–control study) will identify the risk factors for target infections caused by CRE; 248 selected patients from study 1 will be matched with patients with carbapenem-susceptibleEnterobacteriaceae(1:1) and with hospitalised patients (1:3) and will provide a historical cohort of patients with CRE infections. Study 3 (a matched cohort study) will follow patients in study 2 in order to assess mortality, length of stay and hospital costs associated with CRE. All patients will be followed for 30 days. Different, up-to-date statistical methods will be applied to come to unbiased estimates for all 3 studies.Ethics and disseminationBefore-study sites will be initiated, approval will be sought from appropriate regulatory agencies and local Ethics Committees of Research or Institutional Review Boards (IRBs) to conduct the study in accordance with regulatory requirements. This is an observational study and therefore no intervention in the diagnosis, management or treatment of the patients will be required on behalf of the investigation. Any formal presentation or publication of data collected from this study will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE) for authorship.Trial registration numberNCT02709408.
Home or hospital for people with dementia and one or more other multimorbidities: What is the potential to reduce avoidable emergency admissions? The HOMEWARD Project Protocol
Authors: Voss S , Black S , Brandling J , Buswell M , Cheston R , Cullum S , Kirby K , Purdy S , Solway C , Taylor H , Benger J 
Published: April 2017

IntroductionOlder people with multimorbidities frequently access 999 ambulance services. When multimorbidities include dementia, the risk of ambulance use, accident and emergency (A&E) attendance and hospital admission are all increased, even when a condition is treatable in the community. People with dementia tend to do poorly in the acute hospital setting and hospital admission can result in adverse outcomes. This study aims to provide an evidence-based understanding of how older people living with dementia and other multimorbidities are using emergency ambulance services. It will also provide evidence of how paramedics make decisions about taking this group of patients to hospital, and what resources would allow them to make more person-focused decisions to enable optimal patient care.Methods and analysisPhase 1: retrospective data analysis: quantitative analysis of ambulance service data will investigate: how often paramedics are called to older people with dementia; the amount of time paramedics spend on scene and the frequency with which these patients are transported to hospital.Phase 2: observational case studies: detailed case studies will be compiled using qualitative methods, including non-participant observation of paramedic decision-making, to understand why older people with multimorbidities including dementia are conveyed to A&E when they could be treated at home or in the community.Phase 3: needs analysis: nominal groups with paramedics will investigate and prioritise the resources that would allow emergency, urgent and out of hours care to be effectively delivered to these patients at home or in a community setting.Ethics and disseminationApproval for the study has been obtained from the Health Research Authority (HRA) with National Health Service (NHS) Research Ethics Committee approval for phase 2 (16/NW/0803). The dissemination strategy will include publishing findings in appropriate journals, at conferences and in newsletters. We will pay particular attention to dissemination to the public, dementia organisations and ambulance services.