bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated
Salmonella enterica
Serovar Typhimurium Vaccine Strains
Authors: Łaniewski Paweł , Baek Chang-Ho , Roland Kenneth L. , Curtiss Roy 
Published: August 2017

ABSTRACT

Salmonella enterica
serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized
in vivo
. We used an
in vivo
expression technology (IVET) strategy to identify four fimbrial operons,
agf
,
saf
,
sti
, and
stc
that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 × 10
5
CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 × 10
9
CFU of wild-type
S
. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a
Salmonella
vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, χ9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the
Streptococcus pneumoniae
antigen PspA. Strains that constitutively expressed
saf
or
stc
elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying
saf
or
stc
deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent
S. pneumoniae
. Our results indicate that these fimbriae play important roles, as yet not understood, in
Salmonella
virulence and immunogenicity.

IMPORTANCE
Salmonella enterica
is the leading cause of bacterial food-borne infection in the United States. S. Typhimurium is capable of producing up to 13 distinct surface structures called fimbriae that presumably mediate its adherence to surfaces. The roles of most of these fimbriae in disease are unknown. Identifying fimbriae produced during infection will provide important insights into how these bacterial structures contribute to disease and potentially induce protective immunity to
Salmonella
infection. We identified four fimbriae that are produced during infection. Deletion of all four of these fimbriae results in a significant reduction in virulence. We explored ways in which the expression of these fimbriae may be exploited for use in recombinant
Salmonella
vaccine strains and found that production of Saf and Stc fimbriae are important for generating a strong immune response against a vectored antigen. This work provides new insight into the role of fimbriae in disease and their potential for improving the efficacy of
Salmonella
-based vaccines.
Trends in diagnostic patterns and mortality in emergency ambulance service patients in 2007−2014: a population-based cohort study from the North Denmark Region
Authors: Christensen Erika Frischknecht , Bendtsen Mette Dahl , Larsen Thomas Mulvad , Jensen Flemming Bøgh , Lindskou Tim Alex , Holdgaard Hans Ole , Hansen Poul Anders , Johnsen Søren Paaske , Christiansen Christian Fynbo 
Published: August 2017

ObjectiveDemand for ambulances is growing. Nevertheless, knowledge is limited regarding diagnoses and outcomes in patients receiving emergency ambulances. This study aims to examine time trends in diagnoses and mortality among patients transported with emergency ambulance to hospital.DesignPopulation-based cohort study with linkage of Danish national registries.SettingThe North Denmark Region in 2007–2014.ParticipantsCohort of 148 757 patients transported to hospital by ambulance after calling emergency services.Main outcome measuresThe number of emergency ambulance service patients, distribution of their age, sex, hospital diagnoses, comorbidity, and 1-day and 30-day mortality were assessed by calendar year. Poisson regression with robust variance estimation was used to estimate both age-and sex-adjusted relative risk of death and prevalence ratios for Charlson Comorbidity Index (CCI) to allow comparison by year, with 2007 as reference year.ResultsThe annual number of emergency ambulance service patients increased from 24.3 in 2007 to 40.2 in 2014 per 1000 inhabitants. The proportions of women increased from 43.1% to 46.4% and of patients aged 60+ years from 39.9% to 48.6%, respectively. The proportion of injuries gradually declined, non-specific diagnoses increased, especially the last year. Proportion of patients with high comorbidity (CCI≥3) increased from 6.4% in 2007 to 9.4% in 2014, corresponding to an age- and sex-adjusted prevalence ratio of 1.27 (95% CI 1.16 to 1.39). The 1-day and 30 day mortality decreased from 2.40% to 1.21% and from 5.01% to 4.36%, respectively, from 2007 to 2014, corresponding to age-adjusted and sex-adjusted relative risk of 0.43 (95% CI 0.37 to 0.50) and 0.72 (95% CI 0.66 to 0.79), respectively.ConclusionDuring the 8-year period, the incidence of emergency ambulance service patients, the proportion of women, elderly, and non-specific diagnoses increased. The level of comorbidity increased substantially, whereas the 1-day and 30-day mortality decreased.
Longitudinal and secular trends in total cholesterol levels and impact of lipid-lowering drug use among Norwegian women and men born in 1905–1977 in the population-based Tromsø Study 1979–2016
Authors: Hopstock Laila Arnesdatter , Bønaa Kaare Harald , Eggen Anne Elise , Grimsgaard Sameline , Jacobsen Bjarne K , Løchen Maja-Lisa , Mathiesen Ellisiv B , Njølstad Inger , Wilsgaard Tom 
Published: August 2017

ObjectivesElevated blood cholesterol is a modifiable risk factor for cardiovascular disease. Cholesterol level surveillance is necessary to study population disease burden, consider priorities for prevention and intervention and understand the effect of diet, lifestyle and treatment. Previous studies show a cholesterol decline in recent decades but lack data to follow individuals born in different decades throughout life.MethodsWe investigated changes in age-specific and birth cohort-specific total cholesterol (TC) levels in 43 710 women and men born in 1905–1977 (aged 20–95 years at screening) in the population-based Tromsø Study. Fifty-nine per cent of the participants had more than one and up to six repeated TC measurements during 1979–2016. Linear mixed models were used to test for time trends.ResultsMean TC decreased during 1979–2016 in both women and men and in all age groups. The decrease in TC in age group 40–49 years was 1.2 mmol/L in women and 1.0 mmol/L in men. Both the 80th and the 20th percentile of the population TC distribution decreased in both sexes and all age groups. Longitudinal analysis showed that TC increased with age to a peak around middle age followed by a decrease. At any given age, TC significantly decreased with increase in year born. Lipid-lowering drug use was rare in 1994, increased thereafter, but was low (<3% in women and <5% in men) among those younger than 50 years in all surveys. Between 1994 and 2016, lipid-lowering drug treatment in individuals 50 years and older explained 21% and 28% of the decrease in TC levels in women and men, respectively.ConclusionsWe found a substantial decrease in mean TC levels in the general population between 1979 and 2016 in all age groups. In birth cohorts, TC increased with age to a peak around middle age followed by a decrease.
Do hospitalisations for ambulatory care sensitive conditions reflect low access to primary care? An observational cohort study of primary care usage prior to hospitalisation
Authors: Vuik Sabine I , Fontana Gianluca , Mayer Erik , Darzi Ara 
Published: August 2017

ObjectivesTo explore whether hospitalisations for ambulatory care sensitive conditions (ACSCs) are associated with low access to primary care.DesignObservational cohort study over 2008 to 2012 using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases.SettingEnglish primary and secondary care.ParticipantsA random sample of 300 000 patients.Main outcome measuresEmergency hospitalisation for an ACSC.ResultsOver the long term, patients with ACSC hospitalisations had on average 2.33 (2.17 to 2.49) more general practice contacts per 6 months than patients with similar conditions who did not require hospitalisation. When accounting for the number of diagnosed ACSCs, age, gender and GP practice through a nested case–control method, the difference was smaller (0.64 contacts), but still significant (p<0.001).In the short-term analysis, measured over the 6 months prior to hospitalisation, patients used more GP services than on average over the 5 years. Cases had significantly (p<0.001) more primary care contacts in the 6 months before ACSC hospitalisations (7.12, 95% CI 6.95 to 7.30) than their controls during the same 6 months (5.57, 95% CI 5.43 to 5.72). The use of GP services increased closer to the time of hospitalisation, with a peak of 1.79 (1.74 to 1.83) contacts in the last 30 days before hospitalisation.ConclusionsThis study found no evidence to support the hypothesis that low access to primary care is the main driver of ACSC hospitalisations. Other causes should also be explored to understand how to use ACSC admission rates as quality metrics, and to develop the appropriate interventions.
Usage of ambulance transport and influencing factors in acute coronary syndrome: a cross-sectional study at a tertiary centre in China
Authors: Ma Jingjing , Wang Jiali , Zheng Wen , Zheng Jiaqi , Wang Hao , Wang Guangmei , Zhang He , Xu Feng , Chen Yuguo 
Published: August 2017

ObjectivesThe aim of this study was to explore the choice of transportation mode to hospital in patients with acute coronary syndrome (ACS) and to determine the factors influencing the use of ambulance.Design, setting and participantsThis cross-sectional study was conducted in a tertiary and teaching hospital in China. The study was carried out between 24 August 2015 and 24 July 2016. A total of 828 patients with ACS presented at the emergency department (ED) were included. The study population was dichotomised according to their primary mode of transport (ambulance or self-transport) to hospital. Social demographics, cardiovascular history, risk factors, prehospital medications, clinical characteristics and symptom characteristics were collected. Multivariable logistic regression was used to examine the factors associated with ambulance use.ResultsWe found that only 179 (21.6%) patients with ACS chose taking ambulance to hospital. Factors associated with ambulance use were single (OR 1.66, 95% CI 1.07 to 2.57), taking Suxiaojiuxin pills (OR 1.91, 1.31 to 2.80) or nitrates (OR 2.91, 1.70 to 4.99) before going to hospital, diagnosed as ST-elevation myocardial infarction (STEMI) (OR 2.43, 1.45 to 4.05), with persistent symptoms (OR 1.95, 1.33 to 2.86) and symptoms accompanied with vomiting (OR 2.35, 1.19 to 4.62). The patients who had symptoms precipitated or aggravated by exercise (OR 0.37, 0.14 to 0.98) tended to choose self-transport.ConclusionThe usage of ambulance in patients with ACS presenting to the ED was low in China. Factors like single, taking Suxiaojiuxin pills or nitrates before going to hospital, diagnosed as STEMI, accompanied with vomiting and persistent symptoms were independently associated with ambulance use. Future education programmes should focus on these factors and increase people’s knowledge on ACS and the benefits of ambulance use.
Involving clinical experts in prioritising topics for health technology assessment: a randomised controlled trial
Authors: Cook Andrew , Streit Elke , Davage Gill 
Published: August 2017

ObjectivesThe objective of this study was to explore whether reducing the material supplied to external experts during peer review and decreasing the burden of response would maintain review quality into prioritising research questions for a major research funder.Methods and analysisClinical experts who agreed to review documents outlining research for potential commissioning were screened for eligibility and randomised in a factorial design to two types of review materials (long document versus short document) and response modes (structured review form versus free text email response). Previous and current members of the funder’s programme groups were excluded. Response quality was assessed by use of a four-point scoring tool and analysed by intention to treat.Results554 consecutive experts were screened for eligibility and 460 were randomised (232 and 228 to long document or short document, respectively; 230 each to structured response or free text). 356 participants provided reviews, 90 did not respond and 14 were excluded after randomisation as not eligible.The pooled mean quality score was 2.4 (SD=0.95). The short document scored 0.037 (Cohen’s d=0.039) extra quality points over the long document arm, and the structured response scored 0.335 (Cohen’s d=0.353) over free text. The allocation did not appear to have any effect on the experts' willingness to engage with the task.ConclusionsNeither providing a short or a long document outlining suggested research was shown to be superior. However, providing a structured form to guide the expert response provided more useful information than allowing free text. The funder should continue to use a structured form to gather responses. It would be acceptable to provide shorter documents to reviewers, if there were reasons to do so.Trial registration numberANZCTR12614000167662.
Self-reported health status, treatment decision and survival in asymptomatic and symptomatic patients with aortic stenosis in a Western Norway population undergoing conservative treatment: a cross-sectional study with 18 months follow-up
Authors: Oterhals Kjersti , Haaverstad Rune , Nordrehaug Jan Erik , Eide Geir Egil , Norekvål Tone M 
Published: August 2017

ObjectivesTo investigate symptoms and self-reported health of patients conservatively treated for aortic stenosis (AS) and to identify factors associated with treatment decision and patient outcomes.DesignA cross-sectional survey with an 18-month follow-up.SettingOne tertiary university hospital in Western Norway.ParticipantsIn all, 1436 patients were diagnosed with AS between 2000 and 2012, and those 245 still under conservative treatment in 2013 were included in this study.Primary and secondary outcome measuresPrimary outcome measures were symptoms and self-reported health status. Secondary outcomes were treatment decision and patient survival after 18 months.ResultsA total of 136 patients with mean (SD) age 79 (12) years, 52% men responded. Among conservatively treated patients 77% were symptomatic. The symptom most frequently experienced was dyspnoea. Symptomatic patients reported worse physical and mental health compared with asymptomatic patients (effect size 1.24 and 0.74, respectively). In addition, symptomatic patients reported significantly higher levels of anxiety and depression compared with asymptomatic patients. However, symptom status did not correlate with haemodynamic severity of AS. After 18 months, 117 (86%) were still alive, 20% had undergone surgical aortic valve replacement (AVR) and 7% transcatheter aortic valve implantation (TAVI). When adjusting for age, gender, symptomatic status, severity of AS and European system for cardiac operative risk evaluation (EuroSCORE), patients with severe AS had more than sixfold chance of being scheduled for AVR or TAVI compared with those with moderate AS (HR 6.3, 95% CI 1.9 to 21.2, p=0.003). Patients with EuroSCORE ≥11 had less chance for undergoing AVR or TAVI compared with those with EuroSCORE ≤5 (HR 0.06, 95% CI 0.01 to 0.46, p=0.007).ConclusionsSymptoms affected both physical and mental health in conservatively treated patients with AS. Many patients with symptomatic severe AS are not scheduled for surgery, despite the recommendations in current guidelines. The referral practice for AVR is a path for further investigation.
A systematic review and meta-analysis of trials of social network interventions in type 2 diabetes
Authors: Spencer-Bonilla Gabriela , Ponce Oscar J , Rodriguez-Gutierrez Rene , Alvarez-Villalobos Neri , Erwin Patricia J , Larrea-Mantilla Laura , Rogers Anne , Montori Victor M 
Published: August 2017

ObjectivesIn the care of patients with type 2 diabetes, self-management is emphasised and studied while theory and observations suggest that patients also benefit from social support. We sought to assess the effect of social network interventions on social support, glycaemic control and quality of life in patients with type 2 diabetes.Research design and methodsWe searched Ovid MEDLINE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO and CINAHL through April 2017 for randomised clinical trials (RCTs) of social network interventions in patients with type 2 diabetes. Reviewers working independently and in duplicate assessed eligibility and risk of bias, and extracted data from eligible RCTs. We pooled estimates using inverse variance random effects meta-analysis.ResultsWe found 19 eligible RCTs enrolling 2319 participants. Social network interventions were commonly based on individual behaviour change rather than social or interpersonal theories of self-management, were educational, and sought to engage social network members for their knowledge and experience. Interventions improved social support (0.74 SD (95% CI 0.32 to 1.15), I2=89%, 8 RCTs) and haemoglobin A1c at 3 months (−0.25 percentage points (95% CI −0.40 to -0.11), I2=12%, 9 RCTs), but not quality of life.ConclusionsDespite a compelling theoretical base, researchers have only minimally studied the value of interventions targeting patients’ social networks on diabetes care. Although the body of evidence to date is limited, and based on individual behaviour change theories, the results are promising. This review challenges the scientific community to design and test theory-based interventions that go beyond self-management approaches to focus on the largely untapped potential of social networks to improve diabetes care.PROSPERO registrationCRD42016036117.
Polymorphisms of the stem cell marker geneCD133are associated the clinical outcome in a cohort of Chinese non-small cell lung cancer patients
Authors: Liu Qing-Feng , Zhang Zhi-Fei , Hou Guang-Jie , Yang Guang-Yu , He Yi 
Published: August 2017

ObjectivesTo evaluate the prognostic relevance of four functional single nucleotide polymorphisms (SNPs) inCD133(rs2240688A>C,rs10022537T>A,rs7686732C>G, andrs3130C>T) on overall survival (OS) of non-small cell lung cancer (NSCLC) patients.DesignRetrospective cohort study.SettingDepartment of General Surgery, in a general hospital, Henan Province, China.ParticipantsNSCLC patients aged ≥18 years, who were not receiving preoperative neoadjuvant therapies and had a blood sample available for genotyping, were eligible for inclusion. Those participants who were pregnant or breastfeeding, had a previous history of cancer, had other primary tumours, or who had had primary tumours of the skin and nasopharynx, were excluded from the study.Outcome measuresThe primary endpoint was OS, which was calculated from the date of enrolment until the date of death or date of last follow-up.ResultsThere was a total of 1383 participants, with a median age of 63 years; 726 (52.5%) were male. Compared with thers2240688AA genotype, the variant AC/CC genotypes were independently associated with OS (HR 1.27, 95% CI 1.12 to 1.45 for AC genotype; HR 2.32, 95% CI 1.91 to 2.80 for CC genotype). Higher hazard ratios for associations betweenCD133 rs2240688polymorphism and OS were observed in patients with adjuvant chemotherapy (HR 1.86, 95% CI 1.52 to 2.26) and radiotherapy for curative intent (HR 1.90, 95% CI 1.55 to 2.33).ConclusionsThe study confirmed the significant association between the SNPrs2240688 A>Cof CD133 and OS of NSCLC patients. Larger population-based studies in different ethnic groups are necessary to further validate the role and mechanisms ofCD133in NSCLC.
RADAR study: protocol for an observational cohort study to identify early warning signals on the pathways to alcohol use disorder
Authors: Slade Tim , Swift Wendy , Mewton Louise , Kypri Kypros , Lynskey Michael T , Butterworth Peter , Tibbetts Joel , McCraw Stacey , Upton Emily 
Published: August 2017

IntroductionHarmful alcohol consumption, particularly alcohol use disorder (AUD), is a worldwide health priority, contributing substantially to global morbidity and mortality. The peak age of onset of AUD is 18–24, thus a deeper understanding of the young adult experience is vital if we are to identify modifiable risk factors and intervene early in the developmental course of this disabling disorder. Critical unanswered questions include: How soon after drinking initiation do AUD symptoms begin to emerge? Which symptoms come first? Do the symptoms unfold in a predictable pattern? In what ways do the emerging symptoms interact with individual, peer, family and environmental risk factors to impact on the transition to disorder?Methods and analysisThe proposed RADAR study will examine the prospective development of AUD symptoms over the young adulthood (18–24) years. We will capitalise on an existing cohort of 1911 community-based adolescents who were recruited at age 13 and have completed a baseline and five annual follow-up assessments as part of an observational cohort study. We will interview these adolescents every 6 months between the ages of 19 and 23 to derive monthly histories of both alcohol use and AUD symptomatology, along with a comprehensive battery of risk and protective factor scales hypothesised to predict the emergence and course of AUD. The results of this study will inform the natural history of AUD and will be used to identify specific targets for prevention and early intervention of AUD.Ethics and disseminationEthical approval has already been granted for the study (UNSW HREC 10144). We will disseminate the results of the study through published manuscripts, conferences and seminar presentations. Data used in published manuscripts will be made available through a suitable online repository (eg, Dryad–datadryad.org).