bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Typhoid Toxin Produced by the Nontyphoidal
Salmonella enterica
Serotype Javiana Is Required for Induction of a DNA Damage Response
In Vitro
and Systemic Spread
In Vivo
Authors: Miller Rachel A. , Betteken Michael I. , Guo Xiaodong , Altier Craig , Duhamel Gerald E. , Wiedmann Martin 
Published: March 2018

ABSTRACT

The
Salmonella
cytolethal distending toxin (S-CDT), first described as the “typhoid toxin” in
Salmonella enterica
subsp.
enterica
serotype Typhi, induces DNA damage in eukaryotic cells. Recent studies have shown that more than 40 nontyphoidal
Salmonella
(NTS) serotypes carry genes that encode S-CDT, yet very little is known about the activity, function, and role of S-CDT in NTS. Here we show that deletion of genes encoding the binding subunit (
pltB
) and a bacteriophage muramidase predicted to play a role in toxin export (
ttsA
) does not abolish toxin activity in the S-CDT-positive NTS
Salmonella enterica
subsp.
enterica
serotype Javiana. However,
S.
Javiana strains harboring deletions of both
pltB
and its homolog
artB
, had a complete loss of S-CDT activity, suggesting that
S.
Javiana carries genes encoding two variants of the binding subunit. S-CDT-mediated DNA damage, as determined by phosphorylation of histone 2AX (H2AX), producing phosphorylated H2AX (γH2AX), was restricted to epithelial cells in S and G
2
/M phases of the cell cycle and did not result in apoptosis or cell death. Compared to mice infected with a Δ
cdtB
strain, mice infected with wild-type
S.
Javiana had significantly higher levels of
S.
Javiana in the liver, but not in the spleen, ileum, or cecum. Overall, we show that production of active S-CDT by NTS serotype
S.
Javiana requires different genes (
cdtB
,
pltA
, and either
pltB
or
artB
) for expression of biologically active toxin than those reported for S-CDT production by
S.
Typhi (
cdtB
,
pltA
,
pltB
, and
ttsA
). However, as in
S.
Typhi, NTS S-CDT influences the outcome of infection both
in vitro
and
in vivo
.

IMPORTANCE
Nontyphoidal
Salmonella
(NTS) are a major cause of bacterial food-borne illness worldwide; however, our understanding of virulence mechanisms that determine the outcome and severity of nontyphoidal salmonellosis is incompletely understood. Here we show that S-CDT produced by NTS plays a significant role in the outcome of infection both
in vitro
and
in vivo
, highlighting S-CDT as an important virulence factor for nontyphoidal
Salmonella
serotypes. Our data also contribute novel information about the function of S-CDT, as S-CDT-mediated DNA damage occurs only during certain phases of the cell cycle, and the resulting damage does not induce cell death as assessed using a propidium iodide exclusion assay. Importantly, our data support that, despite having genetically similar S-CDT operons, NTS serotype
S.
Javiana has different genetic requirements than
S.
Typhi, for the production and export of active S-CDT.
Regulation of the IL-33/ST2 Pathway Contributes to the Anti-Inflammatory Effect of Acupuncture in the Ovalbumin-Induced Murine Asthma Model
Authors: Dong Ming , Ma Cheng , Wang Wen-Qian , Chen Juan , Wei Ying 
Published: March 2018

Background Bronchial asthma is a chronic airway inflammatory disease which has three main pathological features: airway hyperresponsiveness (AHR), airway remodelling, and chronic inflammation. Acupuncture is known to be an effective integrative medical therapy that has been used in the treatment of several chronic diseases, including bronchial asthma. The aim of the current study was to evaluate the effects of acupuncture on inflammation and regulation of the IL-33/ST2 pathway in a mouse model of asthma. Methods The murine asthma model was established by both injection and inhalation of ovalbumin (OVA). Within 24 hours of the last OVA challenge, lung function was assessed by measurement of the airway resistance (RL) and lung dynamic compliance (Cdyn). Pulmonary tissues were collected for the detection of pathological changes and mucus secretion. Serum levels of tumour necrosis factor α (TNF-α), interleukin (IL)-1β, IL-33 and sST2 (secreted ST2) were detected by ELISA. Th17 cell proportions and counts in bronchoalveolar lavage fluid (BALF) were analysed by flow cytometry. Results The results showed that AHR, chronic inflammation and mucus secretion were significantly suppressed by acupuncture treatment. RL decreased while Cdyn increased after acupuncture treatment. There was an apparent decrease in the serum concentrations of certain pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-33, and an increase in sST2 level compared with untreated asthmatic mice. Acupuncture also reduced the CD4 +IL-17A+ cell proportion and counts in BALF. Conclusion Acupuncture effectively protects lung function and attenuates airway inflammation in the OVA-induced mouse model of asthma, which supports the role of acupuncture as a potential therapy in asthma treatment.
Is exposure to ionising radiation associated with childhood cardiac arrhythmia in the Russian territories contaminated by the Chernobyl fallout? A cross-sectional population-based study
Authors: Jourdain Jean-Rene , Landon Geraldine , Clero Enora , Doroshchenko Vladimir , Silenok Aleksandr , Kurnosova Irina , Butsenin Andrei , Denjoy Isabelle , Franck Didier , Heuze Jean-Pierre , Gourmelon Patrick 
Published: March 2018

ObjectiveTo investigate childhood cardiac arrhythmia and chronic exposure to caesium-137 (137Cs) resulting from the Chernobyl accident.DesignProspective cross-sectional study using exposed/unexposed design conducted in the Bryansk region from May 2009 to May 2013 on children selected on the basis of137Cs soil deposition: control territories ([137Cs]<37 kBq per square metre, where children were considered as unexposed) and contaminated territories ([137Cs]>555 kBq per square metre, where children were considered as exposed).SettingRussian territories affected by the Chernobyl fallout (Bryansk region).ParticipantsThis cross-sectional study included 18 152 children aged 2–18 years and living in the Bryansk region (Russia).Main outcome measuresAll children received three medical examinations (ECG, echocardiography and137Cs whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests.ResultsCardiac arrhythmia was diagnosed in 1172 children living in contaminated territories and 1354 children living in control territories. The crude prevalence estimated to 13.3% in contaminated territories was significantly lower than in control territories with 15.2% over the period 2009–2013 (P<0.001). Considering137Cs whole-body burden as exposure, cardiac arrhythmia was found in 449 contaminated children and 2077 uncontaminated children, corresponding to an estimated crude prevalence of 14.5% and 14.2%, respectively, which does not differ significantly (P=0.74). Also, we investigated the association between territory, exposure to137Cs and cardiac arrhythmia: the adjusted OR was not significant (0.90 with 95% CI 0.81 to 1.00; P=0.06) for the territory. For137Cs whole-body burden, the ORs close to 1 did not reach statistical significance (P for trend=0.97).ConclusionThis study does not observe an association between cardiac arrhythmia and137Cs deposition levels in the Bryansk region exposed to Chernobyl fallout. The suspected increase of cardiac arrhythmia in children exposed to Chernobyl fallout is not confirmed.
Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: a case–control study in a 2-year prospective cohort
Authors: Prato Rosa , Fortunato Francesca , Cappelli Maria Giovanna , Chironna Maria , Martinelli Domenico 
Published: March 2018

ObjectivesCurrent strategies to prevent adult pneumococcal disease have been recently reviewed in Italy. We did a postlicensure study to estimate the direct vaccine effectiveness (VE) of the 13-valent pneumococcal conjugate vaccine (PCV13) against adult pneumococcal community-acquired pneumonia (pCAP).Study designBetween 2013 and 2015, a 2-year prospective cohort study of adults with CAP was conducted in the Apulia region of Italy where the average vaccine uptake of PCV13 was 32% among adults ≥65 years. The test-negative design was used to estimate VE against all episodes of confirmed pCAP and vaccine-type (VT)-CAP. VE in a subgroup of patients managed in the community was also estimated using a matched case–control design. VE was calculated as one minus the OR times 100%.ResultsThe overall VE of PCV13 was 33.2% (95% CI −106.6% to 82%) against pCAP irrespective of serotype and 38.1% (95% CI −131.9% to 89%) against VT-CAP in the cohort of adults ≥65 years. The VE was 42.3% (95% CI −244.1% to 94.7%) against VT-CAP in the age group at higher vaccine uptake. For the subgroup of cases managed in the community, the overall VE against disease due to any pneumococcal strain was 88.1% (95% CI 4.2% to 98.5%) and 91.7% (95% CI 13.1% to 99.2%) when we controlled for underlying conditions.ConclusionsAlthough our results are non-significant, PCV13 promises to be effective against all confirmed pCAP already with modest levels of uptake in the population of adults ≥65 years of age. Larger studies are needed to confirm the direct vaccine benefits.
A cost of illness study of hypoglycaemic events in insulin-treated diabetes in the Netherlands
Authors: de Groot Saskia , Enters-Weijnen Catherine F , Geelhoed-Duijvestijn Petronella H , Kanters Tim A 
Published: March 2018

ObjectivesPatients with diabetes mellitus are at a risk for hypoglycaemia. Besides the burden of hypoglycaemia for patients, hypoglycaemia poses an economic burden to society. The aim of this study was to calculate the per patient societal costs of hypoglycaemia among patients with type1 diabetes (T1DM) and type 2 diabetes (T2DM) on insulin therapy in the Netherlands.MethodsTo calculate the costs of hypoglycaemia, data from the Global Hypoglycaemia Assessment Tool (HAT) study were used. Dutch patients were selected from the HAT study database and data regarding healthcare resource use, informal care use and productivity losses were combined with Dutch unit costs to calculate the per patient 4-week costs of patients experiencing hypoglycaemia. Besides these 4-week costs, costs per hypoglycaemic event were calculated by dividing the study population total 4-week costs by the total number of events in this period.ResultsMean 4-week total costs of hypoglycaemia amounted to €163 (SD, €870) in T1DM and €134 (SD, €364) in T2DM. While productivity costs were the most important cost driver of hypoglycaemia in patients with T1DM (accounting for 72% of the total costs), costs of hypoglycaemia in patients with T2DM were almost entirely driven by costs within the healthcare sector (accounting for 98% of the total costs). Mean costs of a severe hypoglycaemic event were €828 and €508 in T1DM and T2DM, respectively, whereas mean costs of a non-severe event were almost zero.ConclusionsThis study showed that the economic burden of severe hypoglycaemia is substantial. The prevention of hypoglycaemia could therefore not only reduce the burden for patients, but also the economic burden to society.
A systematic assessment of Cochrane reviews and systematic reviews published in high-impact medical journals related to cancer
Authors: Goldkuhle Marius , Narayan Vikram M , Weigl Aaron , Dahm Philipp , Skoetz Nicole 
Published: March 2018

ObjectiveTo compare cancer-related systematic reviews (SRs) published in the Cochrane Database of SRs (CDSR) and high-impact journals, with respect to type, content, quality and citation rates.DesignMethodological SR with assessment and comparison of SRs and meta-analyses. Two authors independently assessed methodological quality using an Assessment of Multiple Systematic Reviews (AMSTAR)-based extraction form. Both authors independently screened search results, extracted content-relevant characteristics and retrieved citation numbers of the included reviews using the Clarivate Analytics Web of Science database.Data sourcesCancer-related SRs were retrieved from the CDSR, as well as from the 10 journals which publish oncological SRs and had the highest impact factors, using a comprehensive search in both the CDSR and MEDLINE.Eligibility criteria for selecting studiesWe included all cancer-related SRs and meta-analyses published from January 2011 to May 2016. Methodological SRs were excluded.ResultsWe included 346 applicable Cochrane reviews and 215 SRs from high-impact journals. Cochrane reviews consistently met more individual AMSTAR criteria, notably with regard to an a priori design (risk ratio (RR) 3.89; 95% CI 3.10 to 4.88), inclusion of the grey literature and trial registries (RR 3.52; 95% CI 2.84 to 4.37) in their searches, and the reporting of excluded studies (RR 8.80; 95% CI 6.06 to 12.78). Cochrane reviews were less likely to address questions of prognosis (RR 0.04; 95% CI 0.02 to 0.09), use individual patient data (RR 0.03; 95% CI 0.01 to 0.09) or be based on non-randomised controlled trials (RR 0.04; 95% CI 0.02 to 0.09). Citation rates of Cochrane reviews were notably lower than those for high-impact journals (Cochrane reviews: mean number of citations 6.52 (range 0–143); high-impact journal SRs: 74.45 (0–652)).ConclusionsWhen comparing cancer-related SRs published in the CDSR versus those published in high-impact medical journals, Cochrane reviews were consistently of higher methodological quality, but cited less frequently.
Effects of vaccines in patients with sickle cell disease: a systematic review protocol
Authors: Wiyeh Alison Beriliy , Abdullahi Leila Hussein , Wonkam Ambroise , Wiysonge Charles Shey , Kaba Mamadou 
Published: March 2018

IntroductionSickle cell disease (SCD) is an inherited haematological disorder caused by a single point mutation (Glub6Val) that promotes polymerisation of haemoglobin S and sickling of erythrocytes. Inflammation, haemolysis, microvascular obstruction and organ damage characterise the highly variable clinical expression of SCD. People with SCD are at increased risk of severe infections, hence the need for vaccination against common disease-causing organisms in this population. We aim to review the evidence on the efficacy and safety of vaccines in people with SCD.Methods and analysisThe present systematic review will examine the current data as indexed in PubMed, CENTRAL, EMBASE and EBSCOHost. We will consult Strategic Advisory Group of Experts practice statements, conference abstracts, reference lists of relevant articles, WHO ICTRP trial registry and experts in the field. Two authors will independently screen search outputs, select studies, extract data and assess risk of bias; resolving discrepancies by discussion and consensus between the two authors or arbitration by a third author when necessary. We will perform a meta-analysis for clinically homogenous studies. Evidence from clinically diverse studies will be aggregated using narrative synthesis of the findings. In either case, we will use the GRADE approach to assess the strength of the available evidence.Ethics and disseminationThe study draws on data that are readily available in the public domain, hence no formal ethical review and approval is required. The findings of this review will be disseminated through conference presentations and a publication in a peer-reviewed journal.PROSPERO registration numberCRD42018084051.
How the science of injury prevention contributes to advancing home fire safety in the USA: successes and opportunities
Authors: Gielen Andrea C , Frattaroli Shannon , Pollack Keshia M , Peek-Asa Corinne , Yang Jingzhen G 
Published: March 2018

BackgroundIn the decades since the landmark report-America Burning-was published in 1973, the number of home fire deaths has shrunk from >5500 per year to 2650 in 2015. This paper: (1) describes how science and practice in injury prevention and fire and life safety contributed to successful interventions, and (2) identifies emerging strategies and future opportunities to prevent home fire-related deaths.MethodsThe aims are addressed through the lens of population health research, with a focus on the work of selected Centers for Disease Control and Prevention-funded Injury Control Research Centers. Results are organised using the Haddon Matrix and an ecological model.ResultsWe found evidence to support interventions that address all components of both the matrix and the model, including: reduced ignition propensity cigarettes, stop smoking campaigns, housing codes, residential sprinkler systems, smoke alarms, community risk reduction, school-based educational programmes, and fire and burn response systems. Future reductions are likely to come from enhancing residential sprinkler and smoke alarm technology, and increasing their utilisation; expanding the use of community risk reduction methods; and implementing new technological solutions. Despite the successes, substantial disparities in home fire death rates remain, reflecting underlying social determinants of health.ConclusionMost of the evidence-supported interventions were focused on changing the policy and community environments to prevent home fires and reduce injury when a fire occurs. Future prevention efforts should give high priority to addressing the continued disparities in home fire deaths.
Cause-specific mortality in Swedish males diagnosed with non-psychotic mental disorders in late adolescence: a prospective population-based study
Authors: Henriksson Malin , Nyberg Jenny , Schiöler Linus , Hensing Gunnel , Kuhn Georg H , Söderberg Mia , Torén Kjell , Löve Jesper , Waern Margda , Åberg Maria 
Published: March 2018

BackgroundWhile risk of premature death is most pronounced among persons with severe mental illness, also milder conditions are associated with increased all-cause mortality. We examined non-psychotic mental (NPM) disorders and specific causes of natural death in a cohort of late adolescent men followed for up to 46 years.MethodsProspective cohort study of Swedish males (n=1 784 626) who took part in structured conscription interviews 1968–2005. 74 525 men were diagnosed with NPM disorders at or prior to conscription. Median follow-up time was 26 years. HRs for cause-specific mortality were calculated using Cox proportional hazards models.ResultsRisks in fully adjusted models were particularly elevated for death by infectious diseases (depressive and neurotic/adjustment disorders (HR 2.07; 95% CI 1.60 to 2.67), personality disorders (HR 2.90; 95% CI 1.96 to 4.28) and alcohol-related and other substance use disorders (HR 9.02; 95% CI 6.63 to 12.27)) as well as by gastrointestinal causes (depressive and neurotic/adjustment disorders (HR 1.64; 95% CI 1.42 to 1.89), personality disorders (HR 2.77; 95% CI 2.27 to 3.38) and alcohol-related/substance use disorders (HR 4.41; 95% CI 3.59 to 5.42)).ConclusionYoung men diagnosed with NPM disorders had a long-term increased mortality risk, in particular due to infectious and gastrointestinal conditions. These findings highlight the importance of early preventive actions for adolescents with mental illness.
High altitude arterialised capillary earlobe blood gas measurement using the Abbott i-STAT
Authors: Lewis Christopher T , Malein W L , Chesner I , Clarke S 
Published: March 2018

IntroductionMeasurement of physiological parameters in extreme environments is essential to advancing knowledge, prophylaxis and treatment of altitude sickness. Point-of-care testing facilitates investigation in non-specialist and remote settings, as well as becoming increasingly popular at the bedside for real-time results in the clinical environment. Arterialised capillary earlobe blood gases are recommended as a valid alternative to arterial sampling in research. This study aimed to test the feasibility of obtaining and analysing daily earlobe samples at high altitude.MethodsFrom 17 to 24 January 2016, 24 participants on a research expedition to Ecuador underwent daily earlobe blood gas measurements including pH, partial pressure of oxygen and partial pressure of carbon dioxide to 5043 m. Samples were analysed using an Abbott i-STAT blood gas analyser and G3+ cartridges.ResultsDaily measurements were successfully obtained and analysed at the point of care in 23/24 participants and were well tolerated with no adverse events. 12% (27/220) cartridges failed and required repeat sampling.ConclusionsDaily earlobe blood gas analysis using the Abbott i-STAT is feasible in a protected environment at high altitude. Participants and equipment should be kept warm before and during testing. Spare cartridges should be available. This methodology may be useful for both research and therapeutic measurements in remote, rural and wilderness medicine.
Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis
Authors: Xie Xue-Feng , Huang Xiao-Hui , Shen Ai-Zong , Li Jun , Sun Ye-Huan 
Published: March 2018

AbstractAimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.
Model-Based Calibration of a Robotic C-Arm System Using X-Ray Imaging
Authors: Thürauf Sabine , Hornung Oliver , Körner Mario , Vogt Florian , Knoll Alois , Nasseri M. Ali 
Published: March 2018

In interventional radiology or surgery, C-arm systems are typical imaging modalities. Apart from 2D X-ray images, C-arm systems are able to perform 2D/3D overlays. For this application, a previously recorded 3D volume is projected on a 2D X-ray image for providing additional information to the clinician. The required accuracy for this application is 1.5[Formula: see text]mm. Such a spatial accuracy is only achievable with C-arms, if a calibration is performed.State-of-the-art approaches interpolate between values of lookup tables of a sampled Cartesian volume. However, due to the non-linear system behavior in Cartesian space, a trade-off between the calibration effort and the calibrated volume is necessary. This leads to the calibration of the most relevant subvolume and high calibration times.We discuss a new model-based calibration approach for C-arm systems which potentially leads to a smaller calibration effort and simultaneously to an increased calibrated volume.In this work, we demonstrate that it is possible to calibrate a robotic C-arm system using X-ray images and that a static model of the system is required to achieve the desired accuracy for 2D/3D overlays, if re-orientations of the system are performed.