bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ralstonia solanacearum Uses Inorganic Nitrogen Metabolism for Virulence, ATP Production, and Detoxification in the Oxygen-Limited Host Xylem Environment
Authors: Dalsing Beth L. , Truchon Alicia N. , Gonzalez-Orta Enid T. , Milling Annett S. , Allen Caitilyn 
Published: March 2015

ABSTRACT

Genomic data predict that, in addition to oxygen, the bacterial plant pathogen
Ralstonia solanacearum
can use nitrate (NO
3
−
), nitrite (NO
2
−
), nitric oxide (NO), and nitrous oxide (N
2
O) as terminal electron acceptors (TEAs). Genes encoding inorganic nitrogen reduction were highly expressed during tomato bacterial wilt disease, when the pathogen grows in xylem vessels. Direct measurements found that tomato xylem fluid was low in oxygen, especially in plants infected by R. solanacearum. Xylem fluid contained ~25 mM NO
3
−
, corresponding to R. solanacearum's optimal NO
3
−
concentration for anaerobic growth
in vitro
. We tested the hypothesis that R. solanacearum uses inorganic nitrogen species to respire and grow during pathogenesis by making deletion mutants that each lacked a step in nitrate respiration (Δ
narG
), denitrification (Δ
aniA
, Δ
norB
, and Δ
nosZ
), or NO detoxification (Δ
hmpX
). The
ΔnarG
,
ΔaniA
, and
ΔnorB
mutants grew poorly on NO
3
−
compared to the wild type, and they had reduced adenylate energy charge levels under anaerobiosis. While NarG-dependent NO
3
−
respiration directly enhanced growth, AniA-dependent NO
2
−
reduction did not. NO
2
−
and NO inhibited growth in culture, and their removal depended on denitrification and NO detoxification. Thus, NO
3
−
acts as a TEA, but the resulting NO
2
−
and NO likely do not. None of the mutants grew as well as the wild type
in planta
, and strains lacking AniA (NO
2
−
reductase) or HmpX (NO detoxification) had reduced virulence on tomato. Thus, R. solanacearum exploits host NO
3
−
to respire, grow, and cause disease. Degradation of NO
2
−
and NO is also important for successful infection and depends on denitrification and NO detoxification systems.

IMPORTANCE
The plant-pathogenic bacterium
Ralstonia solanacearum
causes bacterial wilt, one of the world's most destructive crop diseases. This pathogen's explosive growth in plant vascular xylem is poorly understood. We used biochemical and genetic approaches to show that R. solanacearum rapidly depletes oxygen in host xylem but can then respire using host nitrate as a terminal electron acceptor. The microbe uses its denitrification pathway to detoxify the reactive nitrogen species nitrite (a product of nitrate respiration) and nitric oxide (a plant defense signal). Detoxification may play synergistic roles in bacterial wilt virulence by converting the host's chemical weapon into an energy source. Mutant bacterial strains lacking elements of the denitrification pathway could not grow as well as the wild type in tomato plants, and some mutants were also reduced in virulence. Our results show how a pathogen's metabolic activity can alter the host environment in ways that increase pathogen success.
Stress Granules Regulate Double-Stranded RNA-Dependent Protein Kinase Activation through a Complex Containing G3BP1 and Caprin1
Authors: Reineke Lucas C. , Kedersha Nancy , Langereis Martijn A. , van Kuppeveld Frank J. M. , Lloyd Richard E. 
Published: March 2015

ABSTRACT
Stress granules (SGs) are dynamic cytoplasmic repositories containing translationally silenced mRNAs that assemble upon cellular stress. We recently reported that the SG nucleating protein G3BP1 promotes antiviral activity and is essential in double-stranded RNA-dependent protein kinase (PKR) recruitment to stress granules, thereby driving phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we delineate the mechanism for SG-dependent PKR activation. We show that G3BP1 and inactive PKR directly interact with each other, dependent on both the NTF2-like and PXXP domains of G3BP1. The G3BP1-interacting protein Caprin1 also directly interacts with PKR, regulates efficient PKR activation at the stress granule, and is also integral for the release of active PKR into the cytoplasm to engage in substrate recognition. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. Our data links stress responses and their resultant SGs with innate immune activation through PKR without a requirement for foreign double-stranded RNA (dsRNA) pattern recognition.

IMPORTANCE
Our previous work indicates that stress granules have antiviral activity and mediate innate immunity through functions of G3BP1; however, the mechanistic details of these functions were not resolved. We show that much of the antiviral activity of stress granules is contingent on the function of PKR in a complex with G3BP1 and Caprin1. The PKR-G3BP1-Caprin1 complex undergoes dynamic transitioning within and outside stress granules to accomplish PKR activation and translational repression. This mechanism appears to function distinctly from canonical pattern recognition of double-stranded RNA by PKR. Therefore, this mechanism bridges the stress response with innate immunity, allowing the cell to respond to many cellular stressors and amplify the pathogen pattern recognition systems of innate immunity.
Defining normal ranges and centiles for heart and respiratory rates in infants and children: a cross-sectional study of patients attending an Australian tertiary hospital paediatric emergency department
Authors: O'Leary Fenton , Hayen Andrew , Lockie Francis , Peat Jennifer 
Published: March 2015

ObjectiveKey components in the assessment of a child in the emergency department (ED) are their heart and respiratory rates. In order to interpret these signs, practitioners must know what is normal for a particular age. The aim of this paper is to develop age-specific centiles for these parameters and to compare centiles with the previously published work of Fleming and Bonafide, and the Advanced Paediatric Life Support (APLS) reference ranges.DesignA retrospective cross-sectional study.SettingThe ED of the Children's Hospital at Westmead, Australia.PatientsAfebrile, Triage Category 5 (low priority) patients aged 0–15 years attending the ED.InterventionsCentiles were developed using quantile regression analysis, with cubic B-splines to model the centiles.Main outcome measuresCentile charts were compared with previous studies by concurrently plotting the estimates.Results668 616 records were retrieved for ED attendances from 1995 to 2011, and 111 696 heart and respiratory rates were extracted for inclusion in the analysis. Graphical comparison demonstrates that with heart rate, our 50th centile agrees with the results of Bonafide, is considerably higher than the Fleming centiles and fits well between the APLS reference ranges. With respiratory rate, our 50th centile was considerably lower than the comparison centiles in infants, becomes higher with increasing age and crosses the lower APLS range in infants and upper range in teenagers.ConclusionsClinicians should consider adopting these centiles when assessing acutely unwell children. APLS should review their normal values for respiratory rate in infants and teenagers.
Predicting severe motor impairment in preterm children at age 5 years
Authors: Synnes Anne , Anderson Peter J , Grunau Ruth E , Dewey Deborah , Moddemann Diane , Tin Win , Davis Peter G , Doyle Lex W , Foster Gary , Khairy May , Nwaesei Chukwuma , Schmidt Barbara 
Published: March 2015

ObjectiveTo determine whether the ability to predict severe motor impairment at age 5 years improves between birth and 18 months.DesignAncillary study of the Caffeine for Apnea of Prematurity Trial.Setting and PatientsInternational cohort of very low birth weight children who were assessed sequentially from birth to 5 years.Outcome MeasuresSevere motor impairment was defined as a score <5th percentile on the Movement Assessment Battery of Children (MABC), or inability to complete the MABC because of cerebral palsy. Multivariable logistic regression cumulative risk models used four sets of predictor variables: early neonatal risk factors, risk factors at 36 weeks’ postmenstrual age, risk factors at a corrected age of 18 months, and sociodemographic variables. A receiver operating characteristic curve (ROC) was generated for each model, and the four ROC curves were compared to determine if the addition of the new set of predictors significantly increased the area under the curve (AUC).ResultsOf 1469 children, 291 (19.8%) had a severe motor impairment at 5 years. The AUC increased from 0.650 soon after birth, to 0.718 (p<0.001) at 36 weeks’ postmenstrual age, and to 0.797 at 18 months (p<0.001). Sociodemographic variables did not significantly improve the AUC (AUC=0.806; p=0.07).ConclusionsPrediction of severe motor impairment at 5 years of age using a cumulative risk model improves significantly from birth to 18 months of age in children with birth weights between 500 g and 1250 g.Trial registration numberClinicalTrials.gov numberNCT00182312.
Estimation of perinatal mortality rate for institutional births in Rajasthan state, India, using capture–recapture technique
Authors: Mony Prem K , Varghese Beena , Thomas Tinku 
Published: March 2015

ObjectiveThe objective of our investigation was to estimate the perinatal mortality rate among institutional births and to compare the sensitivities of different data collection methods.SettingA hospital-based prospective cohort study was undertaken during late-2012 in 21 public sector health facilities of 10 districts of the northern state of Rajasthan, India.ParticipantsA total of 6872 births were included in this epidemiological study.Primary and secondary outcome measuresPerinatal mortality rate of institutional births was the primary outcome. Sensitivities of ‘active’ and passive’ data collection methods were the secondary outcome measures.MethodsAll stillbirth data were from routine government records (‘passive system’); early neonatal outcome data from government records (‘passive’) were compared against the method of ‘phone-tracking’ of outcomes through the community health worker (‘active system’). The Lincoln-Petersen formula for capture-recapture method was used to calculate the probable missing number of early neonatal deaths and thereby estimate the institutional perinatal mortality rate.ResultsRatio of births in district:subdistrict facilities was 55:45. The estimated perinatal mortality rate (95% CI) by capture–recapture method was 35.8 (34 to 37) per 1000 births. The sensitivity of the passive system was 87–89% while the sensitivity of the active system was 91%. Three-fourths of perinatal deaths were documented as stillbirths. However, for these reported intrauterine deaths or stillbirths, clinical classification by typologies (term vs preterm; intrapartum vs antepartum; macerated vs fresh; with or without congenital anomalies) was absent in the recording system.ConclusionsCapture–recapture technique can be used to estimate the institutional perinatal mortality rate and also to assess the level of under-reporting by the ‘passive’ government reporting system. This can subsequently be used for monitoring of trends and studying the impact of health interventions. Accurate clinical categorisation of perinatal deaths is also recommended for improving quality of care.
Socioeconomic status in relation to cardiovascular disease and cause-specific mortality: a comparison of Asian and Australasian populations in a pooled analysis
Authors: Woodward Mark , Peters Sanne A E , Batty G David , Ueshima Hirotsugu , Woo Jean , Giles Graham G , Barzi Federica , Ho Suzanne C , Huxley Rachel R , Arima Hisatomi , Fang Xianghua , Dobson Annette , Lam Tai Hing , Vathesatogkit Prin 
Published: March 2015

ObjectivesIn Western countries, lower socioeconomic status is associated with a higher risk of cardiovascular disease (CVD) and premature mortality. These associations may plausibly differ in Asian populations, but data are scarce and direct comparisons between the two regions are lacking. We, thus, aimed to compare such associations between Asian and Western populations in a large collaborative study, using the highest level of education attained as our measure of social status.SettingCohort studies in general populations conducted in Asia or Australasia.Participants303 036 people (71% from Asia) from 24 studies in the Asia Pacific Cohort Studies Collaboration. Studies had to have a prospective cohort study design, have accumulated at least 5000 person-years of follow-up, recorded date of birth (or age), sex and blood pressure at baseline and date of, or age at, death during follow-up.Outcome measuresWe used Cox regression models to estimate relationships between educational attainment and CVD (fatal or non-fatal), as well as all-cause, cardiovascular and cancer mortality.ResultsDuring more than two million person-years of follow-up, 11 065 deaths (3655 from CVD and 4313 from cancer) and 1809 CVD non-fatal events were recorded. Adjusting for classical CVD risk factors and alcohol drinking, hazard ratios (95% CIs) for primary relative to tertiary education in Asia (Australasia) were 1.81 (1.38, 2.36) (1.10 (0.99, 1.22)) for all-cause mortality, 2.47(1.47, 4.17) (1.24 (1.02, 1.51)) for CVD mortality, 1.66 (1.00, 2.78) (1.01 (0.87, 1.17)) for cancer mortality and 2.09 (1.34, 3.26) (1.23 (1.04, 1.46)) for all CVD.ConclusionsLower educational attainment is associated with a higher risk of CVD or premature mortality in Asia, to a degree exceeding that in the Western populations of Australasia.
Lifelong bound feet in China: a quantitative ultrasound and lifestyle questionnaire study in postmenopausal women
Authors: Qin Ling , Pan Yi , Zhang Ming , Xu Mian , Lao Hanchang , O'Laughlin Michael C , Tong Shan , Zhao Yanling , Hung VWY , Cheng JCY , Guo Xia 
Published: March 2015

ObjectiveThe phenomenon of foot binding, also known as ‘lotus feet’, has an enduring and influential history in China. To achieve a man-made smaller foot size, lifelong foot binding may have had adverse effects on the skeleton. We investigated bone properties in postmenopausal women with bound feet, which may provide new information for developing countermeasures for prevention of fragility fractures.DesignPopulation-based cohort study.ParticipantsThis study involved 254 postmenopausal women aged 65–80, including 172 with bound feet and 82 age- and gender-matched control subjects, living in a remote region of China.OutcomesAnthropometric, SF-36 Lifestyle Questionnaire and heel quantitative ultrasound (QUS) data were collected for the whole study population. A small subset of two cases was also invited for assessment of bone mineral density and microarchitecture at the distal tibia using high-resolution peripheral quantitative CT (HR-pQCT) and gait and balance tests.ResultsWomen with bound feet had significantly lower QUS values than age-matched women with normal feet; this was supported by HR-pQCT data. However, SF-36 Questionnaire results did not reveal any statistically significant differences in any categorical responses, including physical functioning, general health vitality and physical component summary score, and number of previous fractures. No impairment of body balance was found in the small subset.ConclusionsThe man-made changes caused by foot binding led to reduced physical activity, making the subjects prone to osteoporosis. Women with bound feet and osteoporosis did not have a higher incidence of fragility fractures than controls. This might be explained by compensation in physical activity to improve body balance, implying the importance of improving or maintaining body balance in overall prevention strategies against fragility fractures.
Lung cancer in South Africa: a forecast to 2025 based on smoking prevalence data
Authors: Winkler Volker , Mangolo Nosimanana J , Becher Heiko 
Published: March 2015

ObjectiveThis study aims to forecast lung cancer mortality with respect to recent changes in smoking prevalence and compares the results to estimates from GLOBOCAN and the Global Burden of Disease study.SettingAn established epidemiological model is applied to detailed smoking prevalence data from South Africa to estimate lung cancer mortality from 2010 to 2025.ParticipantsData from the South Africa Demographic and Health Survey conducted in 2003 was analysed by sex and ethnic group, and combined with longitudinal estimates on smoking prevalence from 1980 to 2010.Primary and secondary outcome measuresResults provide detailed data on tobacco smoking behaviour by age, sex and ethnic group as well as modelled age-adjusted lung cancer mortality and number of yearly lung cancer deaths.ResultsFrom 2010 to 2025, a decrease in age-adjusted lung cancer mortality is shown from 17.1 to 14.1 among men; whereas rates were stable around 7.2 among women. As a consequence, the estimated number of yearly lung cancer deaths is expected to increase slightly for men and more for women. With respect to ethnic groups, male mortality is expected to be highest for Asians and lowest for blacks. Female rates were lowest for Asians and highest for whites and for coloured.ConclusionsMortality estimates of this study are close to the WHO mortality database and to Global Burden of Disease estimates for 2010, but significantly lower compared with GLOBOCAN estimates. In conclusion, our study demonstrates the impact of demographic changes and the positive effects of antismoking policy on lung cancer mortality in South Africa. Results may help decision makers to further improve smoking control.
Prevalence and incidence of dyslipidaemia among adults in Africa: a systematic review and meta-analysis protocol
Authors: Noubiap Jean Jacques N , Nansseu Jobert Richie N , Bigna Jean Joel R , Jingi Ahmadou M , Kengne André Pascal 
Published: March 2015

IntroductionCardiovascular disease (CVD) is the leading cause of death globally and disproportionately affects low-income and middle-income countries. Dyslipidaemia is an important modifiable risk factor for CVD. There are important knowledge gaps regarding the population levels of lipid variables and frequency of non-optimal levels in populations within Africa. We propose to conduct a systematic review to determine the prevalence and occurrence of dyslipidaemia in adult populations within countries in Africa.Methods and analysisWe will perform a comprehensive search to identify all possible published and unpublished studies on the prevalence or incidence of dyslipidaemia in Africa reported from 1 January 1980, without language restriction. The scientific databases PubMed MEDLINE, EMBASE and ISI Web of Science will be searched, as well as Grey literature. Following study selection, full-text papers acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, and assess heterogeneity. Prevalence/incidence data will be summarised by country and geographic regions and a meta-analysis will be conducted for variables defined identically across studies. Variance stabilising transformations will be applied as appropriate to the row data before meta-analysis. This systematic review will be reported according to the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies.Ethics and disseminationThe current study is based on published data and as such ethics consideration is not a requirement. This review is expected to provide relevant data to help in quantifying the magnitude of dyslipidaemia in African populations, to emphasise the need for appropriate prevention and control strategies, and to identify research gaps and remaining challenges. The final report of the systematic review in the form of a scientific paper will be published in peer-reviewed journals. Findings will further be presented at conferences and submitted to relevant health authorities.Trial registration numberPROSPERO CRD42014015376.
Mortality meetings in geriatric medicine: strategies for improvement
Authors: Dunbar Joanne , George James 
Published: March 2015

AbstractA large proportion of patients who die in hospital will be under the care of geriatric medicine. Mortality reviews have traditionally used trigger tools to try and identify preventable deaths, but the majority of hospital deaths are not preventable and lapses in care are often very complex. Over a period of 14 months we performed four PDSA cycles to change the focus of mortality meetings within care of the elderly and stroke medicine at Cumberland Infirmary to look beyond preventable deaths. The aim was to maximise learning from mortality meetings to improve patient care.We used collaborative working at a trust and departmental level, moving from trigger tool preparation to a narrative approach, and we set up strategies to focus and disseminate our learning. The mean number of cases discussed per meeting and the mean number of lessons identified per case discussed increased, as did the learning levels (trust, department, individual). Maintaining multidisciplinary input and consolidating lessons learnt was difficult because of clinical commitments and natural staff turnover.
Coronary artery stenosis risk and time course in Kawasaki disease patients: experience at a US tertiary pediatric centre
Authors: Patel Alok Sunil , Bruce Margaret , Harrington Whitney , Portman Michael A 
Published: March 2015

ObjectiveDespite treatment with intravenous immunoglobulin (IVIG), the natural progression to coronary artery stenosis in Kawasaki disease is not well defined and remains a potential cause of long-term morbidity. We present a novel study, at a US tertiary paediatric care centre, identifying risk factors for stenosis.MethodsWe reviewed charts of all children who underwent cardiac catheterisation for coronary artery abnormalities, from 1998 to January 2014, at a tertiary paediatric care centre. Demographic and diagnostic data included time intervals to echocardiographic changes and confirmed catheterisation cases of stenosis. Multivariate survival analysis was used to evaluate risk factors with stenosis formation as the main outcome measure.Results53 children met the inclusion criteria and 18 (34.6%) developed stenosis. Only those with giant coronary aneurysms (GCA) developed stenosis, with the highest risk group overall being children under the age of 6 months (hazard ratio (HR) 2.82 3.79, p=0.004). In a subset of only cases of GCA (33), a majority went on to develop stenosis (18/33). Median time to diagnosis was 190 days. In this group, children under the age of 6 months were again at highest risk (HR 2.62, p=0.04). IVIG administration, sex and ethnicity were not statistically significant predictors.ConclusionsThis retrospective study demonstrates a relatively high incidence of stenosis in children with Kawasaki disease and coronary vascular abnormalities. Overall, a majority of cases with GCA progressed into stenosis, with children under the age of 6 months being at highest risk.