bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prevalence of anti‐K in Canadian prenatal patients
Authors: Goldman Mindy , Lane Debra , Webert Kathryn , Fallis Robert 
Published: May 2015

BACKGROUNDAnti‐KEL1(K) is a major cause of hemolytic disease of the fetus and newborn. We utilized data from prenatal testing of patients in Western Canada to determine the frequency of anti‐K. In Manitoba, we evaluated the frequency of transfusion as the likely cause for alloimmunization. We reviewed international practices to prevent alloimmunization.STUDY DESIGN AND METHODSPrenatal patients undergo antibody screening using an automated testing platform and uniform testing algorithm. Data on the frequency of antibodies, transfusion history, and donor K typing were extracted from the relevant databases at Canadian Blood Services. National standards were reviewed with the help of local experts.RESULTSAnti‐K was found in 397 of 390,193 patients from 2011 to 2013 (1.02 per 1000) and was the second most frequent antibody after anti‐E. In Manitoba, 26 of 75 (35%) anti‐K patients had received transfusions in the province since 2001; 14 of the 26 (54%) had received at least one K+ RBC unit and three had received all K– units, while in nine, donor K typing was incomplete. Only eight of the 26 had previous pregnancies, three with K+ partners. International practice varies; however, prophylactic use of matched or K– units is standard in many European countries.CONCLUSIONSAnti‐K was found in 0.1% of prenatal patients. Although our data on the history of transfusion are incomplete, they demonstrate that transfusion with a K+ unit is a major cause of alloimmunization. Given advances in phenotyping and genotyping technologies, prophylactic matching should be considered in Canada.
N
-Acetyltransferase Genotypes and the Pharmacokinetics and Tolerability of
para
-Aminosalicylic Acid in Patients with Drug-Resistant Pulmonary Tuberculosis
Authors: Sy Sherwin K. B. , de Kock Lizanne , Diacon Andreas H. , Werely Cedric J. , Xia Huiming , Rosenkranz Bernd , van der Merwe Lize , Donald Peter R. 
Published: May 2015

ABSTRACT

The aim of this study was to examine the relationships between
N
-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release
para
-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption. Patients'
NAT1
and
NAT2
genotypes were determined by sequencing and restriction enzyme analysis, respectively. The number of daily vomits was modeled by a Poisson probability mass function. Comparisons of other tolerability measures by regimens, gender, and genotypes were evaluated by a linear mixed-effects model. The covariate effects associated with efavirenz, gender, and
NAT1*3
,
NAT1*14
, and
NAT2*5
alleles corresponded to 25, 37, −17, −48, and −27% changes, respectively, in oral clearance of PAS. The
NAT1*10
allele did not influence drug clearance. The time above the MIC of 1 mg/liter was significantly different between the two regimens but not influenced by the
NAT1
or
NAT2
genotypes. The occurrence and intensity of intolerance differed little between regimens. Four grams of GSR-PAS twice daily but not 8 g once daily ensured concentrations exceeding the MIC (1 mg/liter) throughout the dosing interval; PAS intolerance was not related to maximum PAS concentrations over the doses studied and was not more frequent after once-daily dosing. We confirm that the slow phenotype conferred by the
NAT1*14
and
NAT1*3
alleles resulted in higher PAS exposure but found no evidence of increased activity of the
NAT1*10
allele.
Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells
Authors: Forbester Jessica L. , Goulding David , Vallier Ludovic , Hannan Nicholas , Hale Christine , Pickard Derek , Mukhopadhyay Subhankar , Dougan Gordon 
Published: May 2015

ABSTRACT

The intestinal mucosa forms the first line of defense against infections mediated by enteric pathogens such as salmonellae. Here we exploited intestinal “organoids” (iHOs) generated from human induced pluripotent stem cells (hIPSCs) to explore the interaction of
Salmonella enterica
serovar Typhimurium with iHOs. Imaging and RNA sequencing were used to analyze these interactions, and clear changes in transcriptional signatures were detected, including altered patterns of cytokine expression after the exposure of iHOs to bacteria.
S
. Typhimurium microinjected into the lumen of iHOs was able to invade the epithelial barrier, with many bacteria residing within
Salmonella
-containing vacuoles. An
S
. Typhimurium
invA
mutant defective in the
Salmonella
pathogenicity island 1 invasion apparatus was less capable of invading the iHO epithelium. Hence, we provide evidence that hIPSC-derived organoids are a promising model of the intestinal epithelium for assessing interactions with enteric pathogens.
Gene Transfer Efficiency in Gonococcal Biofilms: Role of Biofilm Age, Architecture, and Pilin Antigenic Variation
Authors: Kouzel Nadzeya , Oldewurtel Enno R. , Maier Berenike 
Published: May 2015

ABSTRACT

Extracellular DNA is an important structural component of many bacterial biofilms. It is unknown, however, to which extent external DNA is used to transfer genes by means of transformation. Here, we quantified the acquisition of multidrug resistance and visualized its spread under selective and nonselective conditions in biofilms formed by
Neisseria gonorrhoeae
. The density and architecture of the biofilms were controlled by microstructuring the substratum for bacterial adhesion. Horizontal transfer of antibiotic resistance genes between cocultured strains, each carrying a single resistance, occurred efficiently in early biofilms. The efficiency of gene transfer was higher in early biofilms than between planktonic cells. It was strongly reduced after 24 h and independent of biofilm density. Pilin antigenic variation caused a high fraction of nonpiliated bacteria but was not responsible for the reduced gene transfer at later stages. When selective pressure was applied to dense biofilms using antibiotics at their MIC, the double-resistant bacteria did not show a significant growth advantage. In loosely connected biofilms, the spreading of double-resistant clones was prominent. We conclude that multidrug resistance readily develops in early gonococcal biofilms through horizontal gene transfer. However, selection and spreading of the multiresistant clones are heavily suppressed in dense biofilms.

IMPORTANCE
Biofilms are considered ideal reaction chambers for horizontal gene transfer and development of multidrug resistances. The rate at which genes are exchanged within biofilms is unknown. Here, we quantified the acquisition of double-drug resistance by gene transfer between gonococci with single resistances. At early biofilm stages, the transfer efficiency was higher than for planktonic cells but then decreased with biofilm age. The surface topography affected the architecture of the biofilm. While the efficiency of gene transfer was independent of the architecture, spreading of double-resistant bacteria under selective conditions was strongly enhanced in loose biofilms. We propose that while biofilms help generating multiresistant strains, selection takes place mostly after dispersal from the biofilm.
Induction of the Nitrate Assimilation
nirA
Operon and Protein-Protein Interactions in the Maturation of Nitrate and Nitrite Reductases in the Cyanobacterium Anabaena sp. Strain PCC 7120
Authors: Frías José E. , Flores Enrique 
Published: May 2015

ABSTRACT

Nitrate is widely used as a nitrogen source by cyanobacteria, in which the nitrate assimilation structural genes frequently constitute the so-called
nirA
operon. This operon contains the genes encoding nitrite reductase (
nirA
), a nitrate/nitrite transporter (frequently an ABC-type transporter;
nrtABCD
), and nitrate reductase (
narB
). In the model filamentous cyanobacterium
Anabaena
sp. strain PCC 7120, which can fix N
2
in specialized cells termed heterocysts, the
nirA
operon is expressed at high levels only in media containing nitrate or nitrite and lacking ammonium, a preferred nitrogen source. Here we examined the genes downstream of the
nirA
operon in
Anabaena
and found that a small open reading frame of unknown function,
alr0613
, can be cotranscribed with the operon. The next gene in the genome,
alr0614
(
narM
), showed an expression pattern similar to that of the
nirA
operon, implying correlated expression of
narM
and the operon. A mutant of
narM
with an insertion mutation failed to produce nitrate reductase activity, consistent with the idea that NarM is required for the maturation of NarB. Both
narM
and
narB
mutants were impaired in the nitrate-dependent induction of the
nirA
operon, suggesting that nitrite is an inducer of the operon in
Anabaena
. It has previously been shown that the nitrite reductase protein NirA requires NirB, a protein likely involved in protein-protein interactions, to attain maximum activity. Bacterial two-hybrid analysis confirmed possible NirA-NirB and NarB-NarM interactions, suggesting that the development of both nitrite reductase and nitrate reductase activities in cyanobacteria involves physical interaction of the corresponding enzymes with their cognate partners, NirB and NarM, respectively.

IMPORTANCE
Nitrate is an important source of nitrogen for many microorganisms that is utilized through the nitrate assimilation system, which includes nitrate/nitrite membrane transporters and the nitrate and nitrite reductases. Many cyanobacteria assimilate nitrate, but regulation of the nitrate assimilation system varies in different cyanobacterial groups. In the N
2
-fixing, heterocyst-forming cyanobacteria, the
nirA
operon, which includes the structural genes for the nitrate assimilation system, is expressed in the presence of nitrate or nitrite if ammonium is not available to the cells. Here we studied the genes required for production of an active nitrate reductase, providing information on the nitrate-dependent induction of the operon, and found evidence for possible protein-protein interactions in the maturation of nitrate reductase and nitrite reductase.
The impact of physical activity on health-related fitness and quality of life for patients with head and neck cancer: a systematic review
Authors: Capozzi Lauren C , Nishimura Kathryn C , McNeely Margaret L , Lau Harold , Culos-Reed S Nicole 
Published: May 2015

BackgroundPatients with head and neck cancer often face a plethora of cancer and treatment-related side effects, negatively impacting their lean body mass, physical functioning, quality of life and fatigue management. Physical activity is a potential mediator of many of these side effects. This is the first systematic review reporting on head and neck cancer and physical activity literature.MethodsA literature search was conducted up to January 2015. Two reviewers independently identified articles using the outlined inclusion criteria, assessing the study methodology, risk of bias and extracting the necessary data from studies evaluating the impact of full-body physical activity on patients with head and neck cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement was used to guide this review.ResultsWe identified 16 articles published from 2003 to 2014, the majority of which were published within the past 5 years. Physical activity interventions were feasible, safe and beneficial in mediating cancer and treatment-related side effects. Specifically, patients experienced improvements in lean body mass, muscular strength, physical functioning, quality of life and fatigue management. Owing to significant study heterogeneity, data were not pooled. Reflecting the early state of the literature, included studies were found to vary greatly in design, quality and reporting characteristics.ConclusionsThere is early evidence that supports the benefit of physical activity interventions for patients with head and neck cancer, both during and following treatment. Future research is necessary to determine the benefits of different physical activity interventions, and their impact on patients with different head and neck cancers.
What is the association of smoking and alcohol use with the increase in social inequality in mortality in Denmark? A nationwide register-based study
Authors: Koch Mette Bjerrum , Diderichsen Finn , Grønbæk Morten , Juel Knud 
Published: May 2015

ObjectivesThe aim of this paper is to estimate the impact of smoking and alcohol use on the increase in social inequality in mortality in Denmark in the period 1985–2009.DesignA nationwide register-based study.SettingDenmark.ParticipantsThe whole Danish population aged 30 years or more in the period 1985–2009.Primary and secondary outcome measuresThe primary outcome is mortality rates in relation to educational attainments calculated with and without deaths related to smoking and alcohol use. An absolute measure of inequality in mortality is applied along with a result on the direct contribution from smoking and alcohol use on the absolute difference in mortality rates. The secondary outcome is life expectancy in relation to educational attainments.ResultsSince 1985, Danish overall mortality rates have decreased. Alongside the improvement in mortality, the absolute difference in the mortality rate (per 100 000 persons) between the lowest and the highest educated quartile grew from 465 to 611 among men and from 250 to 386 among women. Smoking and alcohol use have caused 75% of the increase among men and 97% of the increase among women. Among men the increase was mainly caused by alcohol. In women the increase was mainly caused by smoking.ConclusionsThe main explanation for the increase in social inequality in mortality since the mid-1980s is smoking and alcohol use. A significant reduction in the social inequality in mortality can only happen if the prevention of smoking and alcohol use are targeted to the lower educated part of the Danish population.
Quantitative systematic review of the associations between short-term exposure to nitrogen dioxide and mortality and hospital admissions
Authors: Mills I C , Atkinson R W , Kang S , Walton H , Anderson H R 
Published: May 2015

BackgroundShort-term exposure to NO2has been associated with adverse health effects and there is increasing concern that NO2is causally related to health effects, not merely a marker of traffic-generated pollution. No comprehensive meta-analysis of the time-series evidence on NO2has been published since 2007.ObjectiveTo quantitatively assess the evidence from epidemiological time-series studies published worldwide to determine whether and to what extent short-term exposure to NO2is associated with increased numbers of daily deaths and hospital admissions.DesignWe conducted a quantitative systematic review of 204 time-series studies of NO2and daily mortality and hospital admissions for several diagnoses and ages, which were indexed in three bibliographic databases up to May 2011. We calculated random-effects estimates by different geographic regions and globally, and also tested for heterogeneity and small study bias.ResultsSufficient estimates for meta-analysis were available for 43 cause-specific and age-specific combinations of mortality or hospital admissions (25 for 24 h NO2and 18 of the same combinations for 1 h measures). For the all-age group, a 10 µg/m3increase in 24 h NO2was associated with increases in all-cause, cardiovascular and respiratory mortality (0.71% (95% CI 0.43% to 1.00%), 0.88% (0.63% to 1.13%) and 1.09% (0.75% to 1.42%), respectively), and with hospital admissions for respiratory (0.57% (0.33% to 0.82%)) and cardiovascular (0.66% (0.32% to 1.01%)) diseases. Evidence of heterogeneity between geographical region-specific estimates was identified in more than half of the combinations analysed.ConclusionsOur review provides clear evidence of health effects associated with short-term exposure to NO2although further work is required to understand reasons for the regional heterogeneity observed. The growing literature, incorporating large multicentre studies and new evidence from less well-studied regions of the world, supports further quantitative review to assess the independence of NO2health effects from other air pollutants.
A study of urgent and emergency referrals from NHS Direct within England
Authors: Cook E J , Randhawa G , Guppy A , Large S 
Published: May 2015

ObjectivesThe presented study aimed to explore referral patterns of National Health Service (NHS) Direct to determine how patients engage with telephone-based healthcare and how telephone-based healthcare can manage urgent and emergency care.SettingNHS Direct, England, UKParticipantsNHS Direct anonymised call data (N=1 415 472) were extracted over a representative 1-year period, during the combined month periods of July 2010, October 2010, January 2011 and April 2011. Urgent and emergency calls (N=269 558; 19.0%) were analysed by call factors and patient characteristics alongside symptom classification. Categorical data were analysed using the χ2test of independence with cross-tabulations used to test within-group differences.Primary and secondary outcome measuresUrgent and emergency referrals to 999; accident and emergency or to see a general practitioner urgently, which are expressed as call rate per 100 persons per annum. Outcomes related to symptom variations by patient characteristics (age, gender, ethnicity and deprivation) alongside differences by patient characteristics of call factors (date and time of day).ResultsUrgent and emergency referrals varied by a range of factors relating to call, patient and symptom characteristics. For young children (0–4), symptoms related to ‘crying’ and ‘colds and flu’ and ‘body temperature change’ represented the significantly highest referrals to ‘urgent and emergency’ health services symptoms relating to ‘mental health’ alongside ‘pain’ and ‘sensation disorders’ represented the highest referrals to urgent and emergency health services for adults aged 40+ years.ConclusionsThis study has highlighted characteristics of ‘higher likelihood’ referrals to urgent and emergency care through the delivery of a national nurse-led telephone healthcare service. This research can help facilitate an understanding of how patients engage with both in and out of hours care and the role of telephone-based healthcare within the care pathway.
Improving the handover and care of acute urological admissions
Authors: Bass Edward , Patel Snehal 
Published: May 2015

AbstractThe point at which a patient is most vulnerable during their journey through the hospital as an acute or emergency admission is the point at which they are transferred to the designated oncoming responsible team. Unsurprisingly, inadequate and incomplete clinical handovers have the potential for latter catastrophic consequences and are utterly avoidable. Recognising these facts, good clinical handover is an essential part of clinical governance and patient safety. Perhaps secondarily, clinical handover – especially when conducted with senior surgical personnel – can be a valuable learning tool for the surgical trainee.An complete audit loop was performed to assess the rate of handover and urology registrar involvement in acute urology periods in 2 month long periods as well as the rate of inadequate investigations and treatment. The interventions introduced included foundation doctor induction training in acute urology cases, an explanation of the importance of handover and a reflective look at ourselves and our approachability. As a result there were significant improvements in the rate of early registrar involvement and successful handover for patients admitted under our take.
Influenza vaccination for NHS staff: attitudes and uptake
Authors: Shrikrishna Dinesh , Williams Siân , Restrick Louise , Hopkinson Nicholas S 
Published: May 2015

ObjectivesAnnual vaccination against influenza (flu) is recommended for all UK National Health Service (NHS) staff to help reduce the risk of contracting the virus and transmitting it to patients. However, despite flu campaigns and vaccination promotion, uptake remains low. The aim of this study was to investigate staff attitudes to flu vaccination to see how this may influence their decision to be vaccinated.MethodsAn online survey was sent to staff members across 6 NHS trusts, asking if staff had been vaccinated in the preceding flu season (2013–2014); the survey included questions about beliefs and attitudes to the vaccination, scored on a 5-point Likert scale.Results3059 NHS staff members responded to the survey (86% in the 26–59 age group, 77% female and 84% hospital based). 68% of respondents reported being vaccinated in the preceding year. Using a stepwise regression model, the survey response retained as a positive predictor of having been vaccinated was ‘people working in healthcare should have the flu vaccination every year’ (p<0.001), and the responses retained as negative predictors were ‘the flu vaccination will make me unwell’ (p<0.001) and ‘the flu vaccination was too much trouble for me’ (p<0.001). Analysis by staff group showed a significant difference in the response to ‘the flu vaccination will make me unwell’ between groups (p=0.01), with doctors having a greater tendency to disagree with this statement than other staff members.ConclusionsThese results suggest that addressing NHS staff beliefs around the need for vaccination, while ensuring that practical barriers to having the vaccination are removed, may help to increase uptake. An emphasis on alleviating the concerns of particular staff groups regarding adverse effects of the vaccine may also be of benefit in improving uptake, to protect patients as well as staff.
Outcomes of vertebroplasty compared with kyphoplasty: a systematic review and meta-analysis
Authors: Gu Chris N , Brinjikji Waleed , Evans Avery J , Murad Mohammad H , Kallmes David F 
Published: May 2015

Background and purposeMany studies demonstrate that both kyphoplasty and vertebroplasty are superior to conservative therapy in the treatment of osteoporotic vertebral body compression fractures. We performed a systematic review and meta-analysis of studies comparing the outcomes of vertebroplasty and kyphoplasty, which included prospective non-randomized, retrospective comparative, and randomized studies.Materials and methodsWe searched MEDLINE, EMBASE, and the Web of Science databases for studies of kyphoplasty versus vertebroplasty from 1 January 1990 to 30 November 2014 and compared the following outcomes: procedure characteristics, pain and disability improvement, complications and anatomic outcomes. A subgroup analysis was performed comparing pain outcomes based on the risk of bias.Results29 studies enrolling 2838 patients (1384 kyphoplasty and 1454 vertebroplasty) were included. 16 prospective non-randomized studies, 10 retrospective comparative studies, and 3 randomized controlled studies were included. No significant differences were found in mean pain scores between the two groups postoperatively (2.9±1.5 kyphoplasty vs 2.9±1.7 vertebroplasty, p=0.39) and at 12 months (2.7±1.8 kyphoplasty vs 3.2±1.8 vertebroplasty, p=0.64). No significant differences were found in disability postoperatively (34.7±7.1 kyphoplasty group vs 36.3±7.8 vertebroplasty group, p=0.74) or at 12 months (28.3±16 kyphoplasty group vs 29.6±13.9 vertebroplasty group, p=0.70). Kyphoplasty was associated with lower odds of new fractures (p=0.06), less extraosseous cement leakage (p<0.01), and greater reduction in kyphotic angle (p<0.01).ConclusionsNo significant difference was found between vertebroplasty and kyphoplasty in short- and long-term pain and disability outcomes. Further studies are needed to better determine if any particular subgroups of patients would benefit more from vertebroplasty or kyphoplasty in the treatment of vertebral body compression fractures.