bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tandem Amplification of the Staphylococcal Cassette Chromosome
mec
Element Can Drive High-Level Methicillin Resistance in Methicillin-Resistant Staphylococcus aureus
Authors: Gallagher Laura A. , Coughlan Simone , Black Nikki S. , Lalor Pierce , Waters Elaine M. , Wee Bryan , Watson Mick , Downing Tim , Fitzgerald J. Ross , Fleming Gerard T. A. , O'Gara James P. 
Published: July 2017

ABSTRACT

Hospital-associated methicillin-resistant
Staphylococcus aureus
(MRSA) strains typically express high-level, homogeneous (HoR) β-lactam resistance, whereas community-associated MRSA (CA-MRSA) more commonly express low-level heterogeneous (HeR) resistance. Expression of the HoR phenotype typically requires both increased expression of the
mecA
gene, carried on the staphylococcal cassette chromosome
mec
element (SCC
mec
), and additional mutational event(s) elsewhere on the chromosome. Here the oxacillin concentration in a chemostat culture of the CA-MRSA strain USA300 was increased from 8 μg/ml to 130 μg/ml over 13 days to isolate highly oxacillin-resistant derivatives. A stable, small-colony variant, designated HoR34, which had become established in the chemostat culture was found to have acquired mutations in
gdpP
,
clpX
,
guaA
, and
camS
. Closer inspection of the genome sequence data further revealed that reads covering SCC
mec
were ∼10 times overrepresented compared to other parts of the chromosome. Quantitative PCR (qPCR) confirmed >10-fold-higher levels of
mecA
DNA on the HoR34 chromosome, and MinION genome sequencing verified the presence of 10 tandem repeats of the SCC
mec
element. qPCR further demonstrated that subculture of HoR34 in various concentrations of oxacillin (0 to 100 μg/ml) was accompanied by accordion-like contraction and amplification of the SCC
mec
element. Although slower growing than strain USA300, HoR34 outcompeted the parent strain in the presence of subinhibitory oxacillin. These data identify tandem amplification of the SCC
mec
element as a new mechanism of high-level methicillin resistance in MRSA, which may provide a competitive advantage for MRSA under antibiotic selection.
Modeling the Kinetics of the Permeation of Antibacterial Agents into Growing Bacteria and Its Interplay with Efflux
Authors: Nichols Wright W. 
Published: July 2017

ABSTRACTA mathematical model of the passive permeation of a novel solute into bacteria that explicitly accounts for intracellular dilution through growth was developed. A bacterial cell envelope permeability coefficient of approximately >10−8cm2· s−1is predicted to ensure passive permeation into rapidly replicating bacterial cells. The relative importance of the permeability coefficients of the cytoplasmic and outer membranes of Gram-negative bacteria in determining the overall envelope permeability coefficient was analyzed quantitatively. A mathematical description of the balance between passive influx and active efflux was also developed and shows that bacterial expansion through growth can usually be neglected for compounds likely to be prepared in antibacterial drug discovery programs and the balance between passive inward permeation and active outwardly directed efflux predominates. A new parameter, efflux efficiency (η, where η is equal tok/P, in whichkis the rate coefficient for the efflux pump andPis the permeability coefficient for the membrane across which the pump acts), is introduced, and the consequences for the efficiency of efflux pumping by a single pump, two pumps in parallel across either the cytoplasmic or the outer membrane, and two pumps in series, one across the cytoplasmic membrane and one across the outer membrane of Gram-negative bacteria, are explored. The results, showing additive efficiency for two pumps acting across a single membrane and multiplicative efficiency for two pumps acting in series across the cytoplasmic and outer membranes, can be quantitatively related to the ratios between MICs measured against pump-sufficient and pump deletion strains and agree with those of previous experimental and theoretical studies.
Myocardial infarction masquerading as myocarditis in a patient with factor V Leiden: unmasked with MR
Authors: Walsh Jason Leo , Harris Benjamin Howell Lole , Gharzuddine Walid , Isma'eel Hussain 
Published: July 2017

We present a case of a 21-year-old man presenting with sharp left-sided chest pain. A CT pulmonary angiogram was negative, ECG was unremarkable and a mild troponin rise was observed. Myocarditis was suspected as the most likely diagnosis, particularly in view of the patient’s previous diagnosis of myocarditis 3 years prior. A cardiac MRI was indicative of an acute mid-anterior myocardial infarction (MI) and an old inferior MI with an associated aneurysm. A subsequent angiogram revealed a subtotal occlusion in the second diagonal artery, likely precipitated by homozygous factor V Leiden.This case illustrates the value of MRI in differentiating acute MI from myocarditis when clinical suspicion is low, as in this young patient with atypical chest pain. Further, it demonstrates the value of MRI in detecting previous MIs and reinforces the importance of searching for precipitants of MI in young patients.
Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention
Authors: Hibberd Ashley A , Lyra Anna , Ouwehand Arthur C , Rolny Peter , Lindegren Helena , Cedgård Lennart , Wettergren Yvonne 
Published: July 2017

ObjectiveThe colonic microbiota is altered in patients with colorectal cancer (CRC). We investigated the microbiota composition of patients with colon cancer compared with controls devoid of neoplastic or inflammatory disease and the potential to modify the colonic microbiota with probiotics.DesignBiopsy samples were obtained from the normal mucosa and tumour during colonoscopy from 15 patients with colon cancer. Subsequent patient-matched samples were taken at surgery from the tumour and nearby mucosa from the patients with cancer, eight of whom had received two daily tablets totalling 1.4×1010CFUsBifidobacterium lactisBl-04 and 7×109CFUsLactobacillus acidophilusNCFM. Faecal samples were obtained after colonoscopy prior to starting the intervention and at surgery. In addition, 21 mucosal biopsies from non-cancer controls were obtained during colonoscopy followed by later faecal samples. The colonic and faecal microbiota was assessed by 16S rRNA gene amplicon sequencing.ResultsThe tumour microbiota was characterised by increased microbial diversity and enrichment of several taxa includingFusobacterium,SelenomonasandPeptostreptococcuscompared with the control microbiota. Patients with colon cancer that received probiotics had an increased abundance of butyrate-producing bacteria, especiallyFaecalibacteriumandClostridialesspp in the tumour, non-tumour mucosa and faecal microbiota. CRC-associated genera such asFusobacteriumandPeptostreptococcustended to be reduced in the faecal microbiota of patients that received probiotics.ConclusionsPatients with colon cancer harbour a distinct microbiota signature in the tumour tissue and nearby mucosa, which was altered with probiotic intervention. Our results show promise for potential therapeutic benefits in CRC by manipulation of the microbiota.Trial registration numberNCT03072641; Results.
Clinical and genetic profile of patients with seronegative coeliac disease: the natural history and response to gluten-free diet
Authors: Dore Maria Pina , Pes Giovanni Mario , Dettori Ivana , Villanacci Vincenzo , Manca Alessandra , Realdi Giuseppe 
Published: July 2017

ObjectivesPatients with clinical, genetic and histological features of coeliac disease (CD), but negative for serological markers, pose a significant clinical problem. The aim of this study was to outline a specific profile, and to evaluate the natural history and response to gluten-free diet (GFD) of patients with seronegative CD.Methodspatients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA–DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available.Results48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA−DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42% vs 22%; p<0.05). After a 1-year GFD trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative CD (25%) experienced the occurrence of autoimmune diseases during a median follow-up of 133 months (range 72–192).ConclusionsPatients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.
Protocol for a prospective observational study to improve prehospital notification of injured patients presenting to trauma centres in India
Authors: Mitra Biswadev , Mathew Joseph , Gupta Amit , Cameron Peter , O'Reilly Gerard , Soni Kapil Dev , Kaushik Gaurav , Howard Teresa , Fahey Madonna , Stephenson Michael , Kumar Vineet , Vyas Sharad , Dharap Satish , Patel Pankaj , Thakor Advait , Sharma Naveen , Walker Tony , Misra Mahesh Chandra , Gruen Russell , Fitzgerald Mark 
Published: July 2017

IntroductionPrehospital notification of injured patients enables prompt and timely care in hospital through adequate preparation of trauma teams, space, equipment and consumables necessary for resuscitation, and may improve outcomes. In India, anecdotal reports suggest that prehospital notification, in those few places where it occurs, is unstructured and not linked to a well-defined hospital response. The aim of this manuscript is to describe, in detail, a study protocol for the evaluation of a formalised approach to prehospital notification.Methods and analysisThis is a longitudinal prospective cohort study of injured patients being transported by ambulance to major trauma centres in India. In the preintervention phase, prospective data on patients will be collected on prehospital assessment, notification, inhospital assessment, management and outcomes and recorded in a new tailored multihospital trauma registry. All injured patients arriving by ambulance and allocated to a red or yellow priority category will be eligible for inclusion. The intervention will be a prehospital notification application to be used by ambulance clinicians to notify emergency departments of the impending arrival of a patient. The proportion of eligible patients arriving to hospital after notification will be the primary outcome measure. Secondary outcomes evaluated will be availability of a trauma cubicle, presence of a trauma team on patient arrival, time to first chest X-ray and inhospital mortality.ProgressEthical approval has been obtained from the All India Institute of Medical Sciences, New Delhi and site-specific approval granted by relevant trauma services. The trial has also been registered with the Monash University Human Research and Ethics Committee; Project number: CF16/1814 – 2016000929. Results will be fed back to prehospital and hospital clinicians via a series of reports and presentations. These will be used to facilitate discussions about service redesign and implementation. It is expected that evidence for improved outcomes will enable widespread adoption of this intervention among centres in all settings with less established tools for prehospital assessment and notification.Trial registration numberNCT02877342; Pre-results.
Imbuing medical professionalism in relation to safety: a study protocol for a mixed-methods intervention focused on trialling an embedded learning approach that centres on the use of a custom designed board game
Authors: Ward Marie , McAuliffe Eilish , Ní Shé Éidín , Duffy Ann , Geary Una , Cunningham Una , Holland Catherine , McDonald Nick , Egan Karen , Korpos Christian 
Published: July 2017

IntroductionHealthcare organisations have a responsibility for ensuring that the governance of workplace settings creates a culture that supports good professional practice. Encouraging such a culture needs to start from an understanding of the factors that make it difficult for health professionals to raise issues of concern in relation to patient safety. The focus of this study is to determine whether a customised education intervention, developed as part of the study, with interns and senior house officers (SHOs) can imbue a culture of medical professionalism in relation to patient safety and support junior doctors to raise issues of concern, while shaping a culture of responsiveness and learning.Methods and analysisWe will use quantitative and qualitative methods to collect data. The sample size will be approximately 200 interns and SHOs across the two hospital sites. Two surveys will be included with one measuring leadership inclusiveness and psychological safety and a second capturing information on safety concerns that participants may have witnessed in their places of work. The PlayDecide embedded learning intervention will be developed with key stakeholders. This will be trialled in the middle stage of data collection for both interns and SHOs. A detailed content analysis will be conducted on the surveys to assess any changes in reporting following the PlayDecide intervention. This will be compared with the incident reporting levels and the results of the preintervention and postintervention leadership inclusiveness and psychological safety survey. Statistical analysis will be conducted using SPSS. Differences will be considered statistically significant at p<0.05. Semistructured interviews using a critical incident technique will be used for the ongoing analysis and evaluation of the project. These will be transcribed, de-identified and coded into themes.Ethics and disseminationThe study has been granted ethics approval from University College Dublin (Ref. LS-15–19-Ward-McAuliffe: Imbuing Medical Professionalism in Relation to Safety). The study results will be disseminated through peer-reviewed publications.
Can nurse teachers manage student incivility by guided democracy? A grounded theory study
Authors: Rad Mostafa , Karimi Moonaghi Hossein , Ildarabadi Eshagh 
Published: July 2017

IntroductionManaging incivility in academic settings is among the basic concerns and challenges of most educational systems, including nursing education. Incivility management cannot be considered devoid of disruptive behaviors. However, incivility management is a complexphenomenon upon which few studies are conducted.ObjectivesThe present study aims at discovering teachers and students’ experiences regarding incivility and developing an approach to manage nursing students’ incivility.DesignThe present study was conducted based on the qualitative research design of the grounded theory methodology.SettingsThis study was conducted at schools of nursing in academic settings in Iran.ParticipantsStudy participants in the present study includenurse teachers (N=20) and nursing students (N=9).MethodIn-depth semi-structured interviews were conducted using theoretical and purposive sampling. Constant comparative analysis was used for data analysis.ResultsThe results include four main categories; (1) deterioration of learning; (2) dominant individual and organisational culture; (3) guided democracy; and (4) movement toward professionalism. Guided democracy is recognised as the main basic psychosocial process for incivility management.ConclusionsIncivility management is pursued to help learners develop professional performance. As indicated by the results of the present study, guided democracy is an effective strategy for incivility management in nursing education.
Long-term time trends in incidence, survival and mortality of lymphomas by subtype among adults in Manitoba, Canada: a population-based study using cancer registry data
Authors: Ye Xibiao , Mahmud Salaheddin , Skrabek Pamela , Lix Lisa , Johnston James B 
Published: July 2017

ObjectiveTo examine 30-year time trends in incidence, survival and mortality of lymphomas by subtype in Manitoba, Canada.MethodsLymphoma cases diagnosed between 1984 and 2013 were classified according to the 2008 WHO classification system for lymphoid neoplasms. Death data (1984–2014) were obtained from the Manitoba Vital Statistics Agency. To examine time trends in incidence and mortality, we used joinpoint regression to estimate annual percentage change and average annual percentage change. Age–period–cohort modelling was conducted to measure the effects of age, period and cohort on incidence and mortality time trends. We estimated age-specific and standardised 5-year relative survival and used Poisson regression model to test time trends in relative survival.ResultsTotal Hodgkin lymphoma (HL) incidence in men and women was stable during the study period. Age-standardised total non-Hodgkin lymphoma (NHL) incidence increased by 4% annually until around 2000, and the trend varied by sex and NHL subtype. Total HL mortality continuously declined (by 2.5% annually in men and by 2.7% annually in women), while total NHL mortality increased (by 4.4% annually in men until 1998 and by 3.2% annually in women until 2001) and then declined (by 3.6% annually in men and by 2.5% annually in women). Age-standardised 5-year relative survival for HL improved from 72.6% in 1984–1993 to 85.8% in 2004–2013, and for NHL from 57.0% in 1984–1993 to 67.5% in 2004–2013. Survival improvement was also noted for NHL subtypes, although the extent varied, with the greatest improvement for follicular lymphoma (from 65.3% in 1984–1993 to 87.6% in 2004–2013).ConclusionsTime trends were generally consistent with those reported in other jurisdictions in total HL and NHL incidence, but were unique in incidence for HL and for NHL subtypes chronic/small lymphocytic leukaemia/lymphoma, diffuse large B cell lymphoma and follicular lymphoma. Survival improvements and mortality reductions were seen for HL and NHL in both sexes.
Influence of family history on the willingness of outpatients to undergo genetic testing for salt-sensitive hypertension: a cross-sectional study
Authors: Takeshima Taro , Okayama Masanobu , Ae Ryusuke , Harada Masanori , Kajii Eiji 
Published: July 2017

ObjectivesIt is unclear whether family medical history influences the willingness to undergo genetic testing. This study aimed to determine how family history affected the willingness to undergo genetic testing for salt-sensitive hypertension in patients with and without hypertension.DesignCross-sectional study using a self-administered questionnaire.SettingSix primary care clinics and hospitals in Japan.ParticipantsConsecutive 1705 outpatients aged >20 years, 578 of whom had hypertension.Primary and secondary outcome measuresThe primary outcome variable was the willingness to undergo genetic testing to determine the risk of salt-sensitive hypertension, and the secondary variables were age, sex, education level, family history and concerns about hypertension. Factors associated with a willingness to undergo genetic testing were evaluated in patients with and without hypertension using a logistic regression model.ResultsIn the hypertension and non-hypertension groups, 323 (55.9%) and 509 patients (45.2%), respectively, were willing to undergo genetic testing. This willingness was related with a high level of education (adjusted OR (ad-OR): 1.81, 95% CI 1.12 to 2.93), family history of stroke (1.55, 1.04 to 2.31) and concerns about hypertension (2.04, 1.27 to 3.28) in the hypertension group, whereas in the non-hypertension group, it was influenced by education level (ad-OR: 1.45, 95% CI 1.13 to 1.86), family history of hypertension (1.52, 1.17 to 1.98) and concerns about hypertension (2.03, 1.53 to 2.68).ConclusionsThe influence of family history on the willingness to undergo genetic testing for risk of salt-sensitivity hypertension differed between participants with and without hypertension. In particular, participants without hypertension wished to know their likelihood of developing hypertension, whereas those with hypertension were interested to know the risk of stroke (a complication of hypertension). Family history could help better counsel patients about genetic testing on the basis of their medical history.
Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial)
Authors: Hopewell Sally , Keene David J , Maia Schlüssel Michael , Dritsaki Melina , Dutton Susan , Carr Andrew , Hamilton William , Hansen Zara , Jaggi Anju , Littlewood Chris , Soutakbar Hessam , Heine Peter , Cureton Lucy , Barker Karen , Lamb Sarah E 
Published: July 2017

IntroductionShoulder pain is very common, with around 70% of cases due to disorders of the rotator cuff. Despite widespread provision of physiotherapy, there is uncertainty about which type of exercise and delivery mechanisms are associated with best outcomes. There is also uncertainty around the long-term benefits and harms of corticosteroid injection therapy, which is often used in addition to physiotherapy. The Getting it Right: Addressing Shoulder Pain trial will assess the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder.Methods and analysisWe are conducting a large multicentre randomised controlled trial (2×2 factorial design). We will recruit adults ≥18 years with a new episode of shoulder pain attributable to a rotator cuff disorder as per British Elbow and Shoulder Society guidelines, not currently receiving physiotherapy or being considered for surgery, from at least eight UK National Health Service primary care-based musculoskeletal and related physiotherapy services. Participants (n=704) will be randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (≤6 physiotherapy sessions); (2) best practice advice (one physiotherapy session); (3) corticosteroid injection then progressive exercise (≤6 sessions) or (4) corticosteroid injection then best practice advice (one session). The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score at 12 months. Secondary outcomes are: pain and function SPADI subdomains; health-related quality of life (Five-Level version of the EuroQol EQ-5D-5L); sleep disturbance; return to activity; global impression of change; health resource use; out-of-pocket expenses; work disability. A parallel within-trial economic evaluation will be conducted. The primary analysis will be intention to treat.Ethics and disseminationResearch Ethics Committee approval (REC: 16/SC/0508) has been obtained. Results of the main trial and secondary outcomes will be submitted for publication in a peer-reviewed journal.Trial registration numberISRCTN16539266; EudraCT number: 2016-002991-28.