bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of Essential Genes within a Highly Coordinated Operon in Escherichia coli
Authors: Goh Shan , Hohmeier Angela , Stone Timothy C. , Offord Victoria , Sarabia Francisco , Garcia-Ruiz Cristina , Good Liam 
Published: June 2015

ABSTRACT

Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability of knockout mutants. Essentiality scores for many operon genes remain uncertain. Antisense RNA (asRNA) silencing or in-frame gene disruption of genes may help establish essentiality but can lead to polar effects on genes downstream or upstream of the target gene. Here, the
Escherichia coli
ribF-ileS-lspA-fkpB-ispH
operon was used to evaluate the possibility of independently studying an essential gene using expressed asRNA and target gene overexpression to deregulate coupled expression. The gene requirement for growth in conditional silencing strains was determined by the relationship of target mRNA reduction with growth inhibition as the minimum transcript level required for 50% growth (MTL
50
). Mupirocin and globomycin, the protein inhibitors of IleS and LspA, respectively, were used in sensitization assays of strains containing both asRNA-expressing and open reading frame-expressing plasmids to examine deregulation of the overlapping
ileS-lspA
genes. We found upstream and downstream polar silencing effects when either
ileS
or
lspA
was silenced, indicating coupled expression. Weighted MTL
50
values (means and standard deviations) of
ribF
,
ileS
, and
lspA
were 0.65 ± 0.18, 0.64 ± 0.06, and 0.76 ± 0.10, respectively. However, they were not significantly different (
P
= 0.71 by weighted one-way analysis of variance). The gene requirement for
ispH
could not be determined due to insufficient growth reduction. Mupirocin and globomycin sensitization experiments indicated that
ileS-lspA
expression could not be decoupled. The results highlight the inherent challenges associated with genetic analyses of operons; however, coupling of essential genes may provide opportunities to improve RNA-silencing antimicrobials.
Feed Fermentation with Reuteran- and Levan-Producing Lactobacillus reuteri Reduces Colonization of Weanling Pigs by Enterotoxigenic Escherichia coli
Authors: Yang Yan , Galle Sandra , Le Minh Hong Anh , Zijlstra Ruurd T. , Gänzle Michael G. 
Published: June 2015

ABSTRACT

This study determined the effect of feed fermentation with
Lactobacillus reuteri
on growth performance and the abundance of enterotoxigenic
Escherichia coli
(ETEC) in weanling piglets.
L. reuteri
strains produce reuteran or levan, exopolysaccharides that inhibit ETEC adhesion to the mucosa, and feed fermentation was conducted under conditions supporting exopolysaccharide formation and under conditions not supporting exopolysaccharide formation. Diets were chosen to assess the impact of organic acids and the impact of viable
L. reuteri
bacteria. Fecal samples were taken throughout 3 weeks of feeding; at the end of the 21-day feeding period, animals were euthanized to sample the gut digesta. The feed intake was reduced in pigs fed diets containing exopolysaccharides; however, feed efficiencies did not differ among the diets. Quantification of
L. reuteri
by quantitative PCR (qPCR) detected the two strains used for feed fermentation throughout the intestinal tract. Quantification of
E. coli
and ETEC virulence factors by qPCR demonstrated that fermented diets containing reuteran significantly (
P
< 0.05) reduced the copy numbers of genes for
E. coli
and the heat-stable enterotoxin in feces compared to those achieved with the control diet. Any fermented feed significantly (
P
< 0.05) reduced the abundance of
E. coli
and the heat-stable enterotoxin in colonic digesta at 21 days; reuteran-containing diets reduced the copy numbers of the genes for
E. coli
and the heat-stable enterotoxin below the detection limit in samples from the ileum, the cecum, and the colon. In conclusion, feed fermentation with
L. reuteri
reduced the level of colonization of weaning piglets with ETEC, and feed fermentation supplied concentrations of reuteran that may specifically contribute to the effect on ETEC.
A Minimal Set of Glycolytic Genes Reveals Strong Redundancies in Saccharomyces cerevisiae Central Metabolism
Authors: Solis-Escalante Daniel , Kuijpers Niels G. A. , Barrajon-Simancas Nuria , van den Broek Marcel , Pronk Jack T. , Daran Jean-Marc , Daran-Lapujade Pascale 
Published: June 2015

ABSTRACT

As a result of ancestral whole-genome and small-scale duplication events, the genomes of
Saccharomyces cerevisiae
and many eukaryotes still contain a substantial fraction of duplicated genes. In all investigated organisms, metabolic pathways, and more particularly glycolysis, are specifically enriched for functionally redundant paralogs. In ancestors of the
Saccharomyces
lineage, the duplication of glycolytic genes is purported to have played an important role leading to
S. cerevisiae
's current lifestyle favoring fermentative metabolism even in the presence of oxygen and characterized by a high glycolytic capacity. In modern
S. cerevisiae
strains, the 12 glycolytic reactions leading to the biochemical conversion from glucose to ethanol are encoded by 27 paralogs. In order to experimentally explore the physiological role of this genetic redundancy, a yeast strain with a minimal set of 14 paralogs was constructed (the “minimal glycolysis” [MG] strain). Remarkably, a combination of a quantitative systems approach and semiquantitative analysis in a wide array of growth environments revealed the absence of a phenotypic response to the cumulative deletion of 13 glycolytic paralogs. This observation indicates that duplication of glycolytic genes is not a prerequisite for achieving the high glycolytic fluxes and fermentative capacities that are characteristic of
S. cerevisiae
and essential for many of its industrial applications and argues against gene dosage effects as a means of fixing minor glycolytic paralogs in the yeast genome. The MG strain was carefully designed and constructed to provide a robust prototrophic platform for quantitative studies and has been made available to the scientific community.
Prevalence and clinical significance of cardiac murmurs in schoolchildren
Authors: Kang Guanyang , Xiao Jianmin , Wang Yitong , Wang Jieying , Chen Yuqiang , Liu Qingchun , Chen Qiaozhu , Yang Fan , Li Wei , Chen Jiuhao 
Published: June 2015

ObjectiveTo determine the prevalence and clinical significance of heart murmurs detected during heart disease screening among apparently healthy schoolchildren.DesignCross-sectional study.Setting32 elementary schools in Dongguan City of China.Patients81 213 schoolchildren aged 5–13 years from different elementary schools.Main outcome measuresThe prevalence and clinical significance of heart murmurs among schoolchildren.ResultsMurmurs were detected in 2193 schoolchildren (2.7%), of whom 215 had a structural heart disease (SHD). Of patients who had SHD, 198 children had congenital heart disease (CHD), 12 had mitral valve prolapse and 5 had rheumatic heart disease. In patients who had CHD, the most common diagnosis was a ventricular septal defect. With respect to sex, SHDs were equally distributed between males and females. Of the schoolchildren who had a murmur, 1797 (81.9%) had a murmur with the loudness of grade 1 or 2 and 396 (18.1%) had a murmur with the loudness of grades 3–6. The prevalence of SHD fell significantly with increasing age.ConclusionsThe study suggested that apparently healthy schoolchildren with grade ≤2 cardiac murmurs are least likely to have underlying SHD, especially in those aged ≥10 years. However, echocardiography should be performed in younger schoolchildren with cardiac murmur grade ≥3.
A systematic review protocol examining the effect of vitamin D supplementation on endothelial function
Authors: Alyami A , Soares MJ , Sherriff JL , Zhao Y , Hallett J , Coombes F 
Published: June 2015

IntroductionVitamin D has potential benefits for extraskeletal health. These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction. We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function (EF), possibly through the abrogation of systemic inflammation.Methods and analysisWe will conduct a systematic review of all randomised controlled trials on vitamin D supplementation and EF lasting 12 weeks or more. The search will cover the period 2000–2015 and include studies that describe direct measures of EF, markers of endothelial cell (EC) activation and if concurrently reported, indicators of systemic inflammation. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis. If sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges’ g score, for both fixed and random effect models. I2statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources. Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger's test. Meta-regression analysis (if feasible) will be conducted with restricted maximum likelihood (REML) estimation method, controlling for potential confounders (demographics, study methods, location, etc). A backward elimination process will be applied in the regression modelling procedure. Subgroup analysis, conditional on number of studies retrieved and their sample size, will be stratified on participant disease category, total dose administered, degree of 25(OH)D change and type of supplement used.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the popular press.Trial registration numberInternational Prospective Register for Systematic Reviews (PROSPERO) number CRD42014013523.
Development and evaluation of an online tool for management of overweight children in primary care: a pilot study
Authors: Park Min Hae , Skow Áine , Puradiredja Dewi Ismajani , Lucas Anna , Syrad Hayley , Sovio Ulla , White Billy , Kessel Anthony S , Taylor Barry , Saxena Sonia , Viner Russell M , Kinra Sanjay 
Published: June 2015

ObjectiveTo explore the acceptability of implementing an online tool for the assessment and management of childhood obesity (Computer-Assisted Treatment of CHildren, CATCH) in primary care.Design and settingAn uncontrolled pilot study with integral process evaluation conducted at three general practices in northwest London, UK (November 2012–April 2013).ParticipantsFamilies with concerns about excess weight in a child aged 5–18 years (n=14 children).InterventionFamilies had a consultation with a doctor or nurse using CATCH, which assessed child weight status, cardiometabolic risk and risk of emotional and behavioural difficulties and provided personalised lifestyle advice. Families and practitioners completed questionnaires to assess the acceptability and usefulness of the consultation, and participated in semistructured interviews which explored user experiences.Outcome measuresThe primary outcome was family satisfaction with the tool-assisted consultation. Secondary outcomes were practitioners’ satisfaction, and acceptability and usefulness of the intervention to families and practitioners.ResultsThe majority of families (86%, n=12) and all practitioners (n=4) were satisfied with the consultation. Participants reported that the tool was easy to use, the personalised lifestyle advice useful and the use of visual aids beneficial. Families and practitioners identified a need for practical, structured support for weight management following the consultation.ConclusionsThe results of this pilot study indicate that an online tool for assessment and management of childhood obesity can be implemented in primary care, and is acceptable to patients, families and practitioners. Further development and evaluation of the tool is warranted.
Presentation of respiratory symptoms prior to diagnosis in general practice: a case–control study examining free text and morbidity codes
Authors: Hayward Richard A , Chen Ying , Croft Peter , Jordan Kelvin P 
Published: June 2015

ObjectiveGeneral practitioners can record patients’ presenting symptoms by using a code or free text. We compared breathlessness and wheeze symptom codes and free text recorded prior to diagnosis of ischaemic heart disease (IHD), chronic obstructive pulmonary disease (COPD) and asthma.DesignA case–control study.Setting11 general practices in North Staffordshire, UK, contributing to the Consultations in Primary Care Archive consultation database.ParticipantsCases with an incident diagnosis of IHD, COPD or asthma in 2010 were matched to controls (four per case) with no such diagnosis. All prior consultations with codes for breathlessness or wheeze symptoms between 2004 and 2010 were identified. Free text of cases and controls were also searched for mention of these symptoms.Results592 cases were identified, 194 (33%) with IHD, 182 (31%) with COPD and 216 (37%) with asthma. 148 (25%) cases and 125 (5%) controls had a prior coded consultation for breathlessness. Prevalence of a prior coded symptom of breathlessness or wheeze was 30% in cases, 6% in controls. Median time from first coded symptom to diagnosis among cases was 57 weeks. After adding symptoms recorded in text, prevalence rose to 62% in cases and 25% in controls. Median time from first recorded symptom increased to 144 weeks. The associations between diagnosis of cases and prior symptom codes was strong IHD relative risk ratio (RRR) 3.21 (2.15 to 4.79); COPD RRR 9.56 (6.74 to 13.60); asthma RRR 10.30 (7.17 to 14.90).ConclusionsThere is an association between IHD, COPD and asthma diagnosis and earlier consultation for respiratory symptoms. Symptoms are often noted in free text by GPs long before they are coded. Free text searching may aid investigation of early presentation of long-term conditions using GP databases, and may be an important direction for future research.
Safety of lamotrigine in paediatrics: a systematic review
Authors: Egunsola Oluwaseun , Choonara Imti , Sammons Helen M 
Published: June 2015

ObjectivesTo identify adverse drug reactions associated with lamotrigine in children and compare the safety profile with other antiepileptic drugs.SettingDatabases EMBASE (1974–April 2015), MEDLINE (1946–April 2015), PubMed and the Cochrane library for randomised controlled trials were searched for studies on safety of lamotrigine.ParticipantsAll studies involving paediatric patients aged ≤18 years who have received at least a single dose of lamotrigine with safety as an outcome measure were included.Primary and secondary outcome measuresThe primary outcome measure was safety of lamotrigine. Drug interaction of lamotrigine was the secondary outcome.ResultsA total of 78 articles involving 3783 paediatric patients were identified. There were 2222 adverse events (AEs) reported. Rash was the most commonly reported AE, occurring in 7.3% of the patients. Stevens-Johnson syndrome was rarely reported, with a risk of 0.09 per 100 patients. Discontinuation due to an adverse drug reaction (ADR) was recorded in 72 children (1.9% of all treated patients). Fifty-eight per cent of treatment discontinuation was attributed to different forms of rash and 21% due to increased seizures. Children on lamotrigine monotherapy had lower incidences of AEs. Headache (p=0.02), somnolence (<0.001), nausea (p=0.01), vomiting (p<0.001), dizziness (p<0.001) and abdominal pain (p=0.01) were significantly lower among children on monotherapy.ConclusionsRash was the most common ADR of lamotrigine and the most common reason for treatment discontinuation. Children receiving polytherapy have a higher risk of AEs than monotherapy users.Trial registration numberCRD42013006910.
Predictive model for patients with poor-grade subarachnoid haemorrhage in 30-day observation: a 9-year cohort study
Authors: Szklener Sebastian , Melges Anna , Korchut Agnieszka , Zaluska Wojciech , Trojanowski Tomasz , Rejdak Robert , Rejdak Konrad 
Published: June 2015

ObjectiveThe purpose of this study was to identify prognostic factors and build the predictive model based on poor-grade subarachnoid haemorrhage (SAH) population received only supportive symptomatic treatment.DesignProspective observational cohort study.SettingIntensive care unit at the Clinical Department of Neurology.ParticipantsA total of 101 patients with spontaneous SAH disqualified from neurosurgical operative treatment due to poor clinical condition. Data were collected over a 9-year period.Outcome measuresUnfavourable outcome was defined as a modified Rankin Score ≥5 at 30 days of observation.ResultsMultivariable logistic regression analysis indicated the World Federation of Neurosurgical Societies Scale score, increasing age, Fisher grade and admission leucocytosis as independent predictive factors. The proposed scale subdivides the study population into four prognostic groups with significantly different outcomes: grade I: probability of favourable outcome 89.9%; grade II: 47.5%; grade III: 4.2%; grade IV: 0%. The receiver operating characteristic (ROC) curve for the prediction of outcome performed by the new scale had an area under the curve (AUC)=0.910 (excellent accuracy).ConclusionsUnfavourable outcome in non-operated patients with poor-grade SAH is strongly predicted by traditional unmodifiable factors such as age, amount of bleeding in CT, level of consciousness as well as leucocytosis. A new predictive scale based on the above parameters seems to reliably predict the outcome and may contribute to more effective planning of therapeutic management in patients with poor-grade SAH.
Access and barriers to healthcare in the Kingdom of Saudi Arabia, 2013: findings from a national multistage survey
Authors: El Bcheraoui Charbel , Tuffaha Marwa , Daoud Farah , Kravitz Hannah , AlMazroa Mohammad A , Al Saeedi Mohammad , Memish Ziad A , Basulaiman Mohammed , Al Rabeeah Abdullah A , Mokdad Ali H 
Published: June 2015

ObjectivesWe analysed data from a large household survey to identify barriers to healthcare in the Kingdom of Saudi Arabia.MethodsThe Saudi Health Interview Survey (SHIS) is a national multistage survey of individuals aged 15 years or older. The survey combined a household questionnaire and a laboratory blood analysis. We used a backward elimination multivariate logistic regression model to measure association between (1) diagnosis, (2) treatment, and (3) control of hypertension or diabetes and sociodemographic factors, history of diagnosis with chronic conditions, and type of, and distance travelled to, the clinic last visited.ResultsBetween April and June 2013, a total of 10 735 participants completed SHIS and were invited to the local health clinics. Among hypertensive individuals, women, older individuals, and those previously diagnosed with diabetes and hypercholesterolaemia were more likely to have been diagnosed with hypertension than their counterparts. Among participants diagnosed with hypertension, the likelihood of being treated increased with age and education. The likelihood of having uncontrolled blood pressure despite treatment increased with education and a history of diagnosis with hypercholesterolaemia. Type of clinic visited and distance travelled to last clinic visit were not associated with diagnosis or treatment of hypertension or control of blood pressure. Similar factors were associated with the likelihood of diagnosis and treatment among individuals with diabetes. Having uncontrolled glycated haemoglobin levels, despite treatment, was less common among those who visited governmental clinics other than those of the Ministry of Health, compared with those who visited Ministry clinics.ConclusionsOur findings highlight the importance of individual characteristics in healthcare-seeking practices rather than system-based potential barriers. Saudis seem to mostly seek healthcare when sick. Hence, the Saudi Ministry of Health needs to implement a comprehensive plan including health education and investigations, to understand the barriers and bottlenecks to healthcare-seeking behaviour.
Changes in body mass index and the prevalence of obesity during 1994–2008: repeated cross-sectional surveys and longitudinal analyses. The Tromsø Study
Authors: Jacobsen Bjarne K , Aars Nils Abel 
Published: June 2015

ObjectivesTo determine the mean body mass index (BMI, kg/m2) and prevalence of low weight (BMI<20) and obesity (BMI≥30) in 3 population-based surveys, and to describe the longitudinal changes during 1994–2008 in mean BMI, and the prevalence of low weight and obesity.SettingA population study in Tromsø, Norway.ParticipantsA total of 29 688 different participants in 1 or more of 3 surveys (1994–1995, 2001–2002 and 2007–2008). Longitudinal analyses comprised 9845 participants aged 25–69 in 1994 who participated in the 1994–1995 and 2007–2008 surveys and 4202 men and women who participated in all 3 surveys.Outcome measuresMean age-specific and sex-specific BMI, prevalence of low weight and obesity, and changes in BMI and prevalence of low weight and obesity during 1994–2008, according to sex and birth cohort.ResultsThe age-adjusted (ages 30–84) prevalence of obesity increased from 9.8% and 11.8% in men and women, respectively, in 1994–1995 to 20.9% and 18.5%, respectively, in 2007–2008. The increase in mean age-adjusted BMI was stronger from 1994–1995 to 2001–2002 than from 2001–2002 to 2007–2008. Longitudinal results confirmed that the change in BMI from 1994–1995 to 2001–2002 was larger (0.9 kg/m2(95% CI 0.8 to 1.0) in men and 1.3 kg/m2(95% CI 1.2 to 1.4) in women) than from 2001–2002 to 2007–2008 (0.2 kg/m2(95% CI 0.1 to 0.3) in men and women). The most recently born had the largest increase (p<0.001).ConclusionsThe mean BMI and the prevalence of obesity are still increasing in Tromsø, and the increase is strongest in the youngest age groups. However, the increase in BMI was less marked in the last period (from 2001–2002 to 2007–2008) than in the first period (1994–1995 to 2001–2002).
Improving management of gout in primary care using a customised electronic records template
Authors: Moffat Keith , McNab Duncan 
Published: June 2015

AbstractIt is known that the management of chronic gout in relation to serum uric acid (SUA) monitoring, allopurinol dosing, and lifestyle advice is often sub-optimal in primary care.[1] A quality improvement project in the form of a criterion based audit was carried out in an urban general practice to improve the care of patients being treated for gout.Baseline searching of EMIS confirmed that management of patients with gout who were taking allopurinol was not in line with current guidance. 51(40%) had a SUA checked in the past 12 months, 88(25%) had a SUA below target level, and gout lifestyle advice was not being recorded.An audit was performed to measure and improve the following criteria:• Monitoring of SUA levels in the past 12 months• Titration of urate lowering therapy to bring the SUA below target level• Lifestyle advice in the past 12 monthsAn audit standard of 60% achievement at 2 months and 80% achievement at 4 months was set.The intervention consisted of a custom electronic template within EMIS which allowed guidance of gout management to be displayed and for data to be entered. All members of the team including GPs and administrative staff were educated regarding the intervention. This resulted in a sustained improvement over a 6 month period in all 3 components of the audit with 112(84%) having a SUA level checked, 79(51%) having a SUA below target level and 76(57%) receiving lifestyle advice. Although the improvement did not reach the audit standard in 2 of the criteria it would be expected that outcomes would continue given the systems changes which have been made.