bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosine Phosphorylation and Dephosphorylation in Burkholderia cenocepacia Affect Biofilm Formation, Growth under Nutritional Deprivation, and Pathogenicity
Authors: Andrade Angel , Tavares-Carreón Faviola , Khodai-Kalaki Maryam , Valvano Miguel A. 
Published: November 2015

ABSTRACT

Burkholderia cenocepacia
, a member of the
B. cepacia
complex (Bcc), is an opportunistic pathogen causing serious chronic infections in patients with cystic fibrosis. Tyrosine phosphorylation has emerged as an important posttranslational modification modulating the physiology and pathogenicity of Bcc bacteria. Here, we investigated the predicted bacterial tyrosine kinases BCAM1331 and BceF and the low-molecular-weight protein tyrosine phosphatases BCAM0208, BceD, and BCAL2200 of
B. cenocepacia
K56-2. We show that BCAM1331, BceF, BCAM0208, and BceD contribute to biofilm formation, while BCAL2200 is required for growth under nutrient-limited conditions. Multiple deletions of either tyrosine kinase or low-molecular-weight protein tyrosine phosphatase genes resulted in the attenuation of
B. cenocepacia
intramacrophage survival and reduced pathogenicity in the
Galleria mellonella
larval infection model. Experimental evidence indicates that BCAM1331 displays reduced tyrosine autophosphorylation activity compared to that of BceF. With the artificial substrate
p
-nitrophenyl phosphate, the phosphatase activities of the three low-molecular-weight protein tyrosine phosphatases demonstrated similar kinetic parameters. However, only BCAM0208 and BceD could dephosphorylate BceF. Further, BCAL2200 became tyrosine phosphorylated
in vivo
and catalyzed its autodephosphorylation. Together, our data suggest that despite having similar biochemical activities, low-molecular-weight protein tyrosine phosphatases and tyrosine kinases have both overlapping and specific roles in the physiology of
B. cenocepacia
.
Specific CD4+T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis
Authors: Volz Magdalena Sarah , Moos Verena , Allers Kristina , Luge Enno , Mayer-Scholl Anne , Nöckler Karsten , Loddenkemper Christoph , Jansen Andreas , Schneider Thomas 
Published: November 2015

ABSTRACTClinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4+T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure toLeptospira). Whole-blood specimens were stimulated withLeptospiraantigensin vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4+T cells. The production of inflammatory cytokines such as TNF-α by CD4+T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease.
Functional Analysis of Bacteriophage Immunity through a Type I-E CRISPR-Cas System in Vibrio cholerae and Its Application in Bacteriophage Genome Engineering
Authors: Box Allison M. , McGuffie Matthew J. , O'Hara Brendan J. , Seed Kimberley D. 
Published: November 2015

ABSTRACT

The classical and El Tor biotypes of
Vibrio cholerae
serogroup O1, the etiological agent of cholera, are responsible for the sixth and seventh (current) pandemics, respectively. A genomic island (GI), GI-24, previously identified in a classical biotype strain of
V. cholerae
, is predicted to encode clustered regularly interspaced short palindromic repeat (CRISPR)-associated proteins (Cas proteins); however, experimental evidence in support of CRISPR activity in
V. cholerae
has not been documented. Here, we show that CRISPR-Cas is ubiquitous in strains of the classical biotype but excluded from strains of the El Tor biotype. We also provide
in silico
evidence to suggest that CRISPR-Cas actively contributes to phage resistance in classical strains. We demonstrate that transfer of GI-24 to
V. cholerae
El Tor via natural transformation enables CRISPR-Cas-mediated resistance to bacteriophage CP-T1 under laboratory conditions. To elucidate the sequence requirements of this type I-E CRISPR-Cas system, we engineered a plasmid-based system allowing the directed targeting of a region of interest. Through screening for phage mutants that escape CRISPR-Cas-mediated resistance, we show that CRISPR targets must be accompanied by a 3′ TT protospacer-adjacent motif (PAM) for efficient interference. Finally, we demonstrate that efficient editing of
V. cholerae
lytic phage genomes can be performed by simultaneously introducing an editing template that allows homologous recombination and escape from CRISPR-Cas targeting.

IMPORTANCE
Cholera, caused by the facultative pathogen
Vibrio cholerae
, remains a serious public health threat. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) provide prokaryotes with sequence-specific protection from invading nucleic acids, including bacteriophages. In this work, we show that one genomic feature differentiating sixth pandemic (classical biotype) strains from seventh pandemic (El Tor biotype) strains is the presence of a CRISPR-Cas system in the classical biotype. We demonstrate that the CRISPR-Cas system from a classical biotype strain can be transferred to a
V. cholerae
El Tor biotype strain and that it is functional in providing resistance to phage infection. Finally, we show that this CRISPR-Cas system can be used as an efficient tool for the editing of
V. cholerae
lytic phage genomes.
Regulation of Type IV Pili Contributes to Surface Behaviors of Historical and Epidemic Strains of Clostridium difficile
Authors: Purcell Erin B. , McKee Robert W. , Bordeleau Eric , Burrus Vincent , Tamayo Rita 
Published: November 2015

ABSTRACT

The intestinal pathogen
Clostridium difficile
is an urgent public health threat that causes antibiotic-associated diarrhea and is a leading cause of fatal nosocomial infections in the United States.
C. difficile
rates of recurrence and mortality have increased in recent years due to the emergence of so-called “hypervirulent” epidemic strains. A great deal of the basic biology of
C. difficile
has not been characterized. Recent findings that flagellar motility, toxin synthesis, and type IV pilus (TFP) formation are regulated by cyclic diguanylate (c-di-GMP) reveal the importance of this second messenger for
C. difficile
gene regulation. However, the function(s) of TFP in
C. difficile
remains largely unknown. Here, we examine TFP-dependent phenotypes and the role of c-di-GMP in controlling TFP production in the historical 630 and epidemic R20291 strains of
C. difficile
. We demonstrate that TFP contribute to
C. difficile
biofilm formation in both strains, but with a more prominent role in R20291. Moreover, we report that R20291 is capable of TFP-dependent surface motility, which has not previously been described in
C. difficile
. The expression and regulation of the
pilA1
pilin gene differs between R20291 and 630, which may underlie the observed differences in TFP-mediated phenotypes. The differences in
pilA1
expression are attributable to greater promoter-driven transcription in R20291. In addition, R20291, but not 630, upregulates c-di-GMP levels during surface-associated growth, suggesting that the bacterium senses its substratum. The differential regulation of surface behaviors in historical and epidemic
C. difficile
strains may contribute to the different infection outcomes presented by these strains.

IMPORTANCE
How
Clostridium difficile
establishes and maintains colonization of the host bowel is poorly understood. Surface behaviors of
C. difficile
are likely relevant during infection, representing possible interactions between the bacterium and the intestinal environment. Pili mediate bacterial interactions with various surfaces and contribute to the virulence of many pathogens. We report that type IV pili (TFP) contribute to biofilm formation by
C. difficile
. TFP are also required for surface motility, which has not previously been demonstrated for
C. difficile
. Furthermore, an epidemic-associated
C. difficile
strain showed higher pilin gene expression and greater dependence on TFP for biofilm production and surface motility. Differences in TFP regulation and their effects on surface behaviors may contribute to increased virulence in recent epidemic strains.
Is there an association between tendinopathy and diabetes mellitus? A systematic review with meta-analysis
Authors: Ranger Tom A , Wong Andrea M Y , Cook Jill L , Gaida Jamie E 
Published: November 2015

BackgroundMusculoskeletal symptoms limit adherence to exercise interventions for individuals with type 2 diabetes. People with diabetes may be susceptible to tendinopathy due to chronically elevated blood glucose levels. Therefore, we aimed to investigate this potential association by systematically reviewing and meta-analysing case–control, cross-sectional, and studies that considered both of these conditions.MethodsNine medical databases and hand searching methods were used without year limits to identify all relevant English language articles that considered diabetes and tendinopathy. Two authors applied exclusion criteria and one author extracted data with verification by a second author. Meta-analysis was conducted using a random effects model. Results were expressed as odds ratio (OR), mean difference or standardised mean difference with a confidence intervals (95% CI). Heterogeneity was assessed by I2.Findings31 studies were included in the final analysis of which 26 recruited people with diabetes and five recruited people with tendinopathy. Tendinopathy was more prevalent in people with diabetes (17 studies, OR 3·67, 95% CI 2·71 to 4·97), diabetes was more prevalent in people with tendinopathy (5 studies, OR 1·28, 95% CI 1·10 to 1·49), people with diabetes and tendinopathy had a longer duration of diabetes than people with diabetes only (6 studies, mean difference 5·26 years, 95% CI 4·15 to 6·36) and people with diabetes had thicker tendons than controls (9 studies, standardised mean difference 0·79 95% CI 0·47 to 1·12).InterpretationThese findings provide strong evidence that diabetes is associated with higher risk of tendinopathy. This is clinically relevant as tendinopathy may affect adherence to exercise interventions for diabetes.
Epidemiology of haemodialysis catheter complications: a survey of 865 dialysis patients from 14 haemodialysis centres in Henan province in China
Authors: Wang Kai , Wang Pei , Liang Xianhui , Lu Xiaoqing , Liu Zhangsuo 
Published: November 2015

ObjectivesTo investigate the incidence rates and risk factors for catheter-related complications in different districts and populations in Henan Province in China.DesignCross-sectional.SettingFourteen hospitals in Henan Province.Participants865 patients with renal dysfunction undergoing dialysis using catheters between October 2013 and October 2014.Main outcome measuresThe main outcome measures were complications, risk factors and patient characteristics. Catheter-related complications included catheter-related infection (catheter exit-site infection, catheter tunnel infection and catheter-related bloodstream infection), catheter dysfunction (thrombosis, catheter malposition or kinking, and fibrin shell formation) and central vein stenosis.ResultsThe overall incidence rate was 7.74/1000 catheter-days, affecting 38.61% of all patients, for catheter infections, 10.58/1000 catheter-days, affecting 56.65% of all patients, for catheter dysfunction, and 0.68/1000 catheter-days, affecting 8.79% of all patients, for central vein stenosis. Multivariate analysis showed that increased age, diabetes, primary educational level or below, rural residence, lack of a nephropathy visit before dialysis and pre-established permanent vascular access, not taking oral drugs to prevent catheter thrombus, lower serum albumin levels and higher ferritin levels were independently associated with catheter infections. Rural residence, not taking oral drugs to prevent thrombus, lack of an imaging examination after catheter insertion, non-tunnel catheter type, lack of medical insurance, lack of nephropathy visit before dialysis and pre-established permanent vascular access, left-sided catheter position, access via the femoral vein and lower haemoglobin level were independently associated with catheter dysfunction. Diabetes, lack of nephropathy visit before dialysis and pre-established permanent vascular access, lack of oral drugs to prevent catheter thrombus, left-sided catheter location and higher number of catheter insertions, were independently associated with central vein stenosis.ConclusionsThe rate of catheter-related complications was high in patients with end-stage renal disease in Henan Province. Our finding suggest that strategies should be implemented to decrease complication rates.
Disparities in road crash mortality among pedestrians using wheelchairs in the USA: results of a capture–recapture analysis
Authors: Kraemer John D , Benton Connor S 
Published: November 2015

ObjectiveThis study aims to quantify and describe the burden of fatal pedestrian crashes among persons using wheelchairs in the USA from 2006 to 2012.DesignThe occurrence of fatal pedestrian crashes among pedestrians using wheelchairs was assessed using two-source capture-recapture. Descriptive analysis of fatal crashes was conducted using customary approaches.SettingTwo registries were constructed, both of which likely undercounted fatalities among pedestrians who use wheelchairs. The first used data from the Fatality Analysis Reporting System, and the second used a LexisNexis news search.Outcome measuresMortality rate (per 100 000 person-years) and crash-level, driver-level and pedestrian-level characteristics of fatal crashes.ResultsThis study found that, from 2006 to 2012, the mortality rate for pedestrians using wheelchairs was 2.07/100 000 person-years (95% CI 1.60 to 2.54), which was 36% higher than the overall population pedestrian mortality rate (p=0.02). Men's risk was over fivefold higher than women's risk (p<0.001). Compared to the overall population, persons aged 50–64 using wheelchairs had a 38% increased risk (p=0.04), and men who use wheelchairs aged 50–64 had a 75% increased risk over men of the same age in the overall population (p=0.006). Almost half (47.6%; 95% CI 42.8 to 52.5) of fatal crashes occurred in intersections and 38.7% (95% CI 32.0 to 45.0) of intersection crashes occurred at locations without traffic control devices. Among intersection crashes, 47.5% (95% CI 40.6 to 54.5) involved wheelchair users in a crosswalk; no crosswalk was available for 18.3% (95% CI 13.5 to 24.4). Driver failure to yield right-of-way was noted in 21.4% (95% CI 17.7 to 25.7) of crashes, and no crash avoidance manoeuvers were detected in 76.4% (95% CI 71.0 to 81.2).ConclusionsPersons who use wheelchairs experience substantial pedestrian mortality disparities calling for behavioural and built environment interventions.
Social determinants of HIV infection, hotspot areas and subpopulation groups in Ethiopia: evidence from the National Demographic and Health Survey in 2011
Authors: Lakew Yihunie , Benedict Susan , Haile Demewoz 
Published: November 2015

ObjectiveThis study identifies social determinants of HIV infection, hotspot areas and subpopulation groups in Ethiopia.DesignThe study used data from the 2011 Ethiopian Demographic and Health Survey (EDHS). Sample blood tests from the finger pricks collected on filter paper cards were labelled with a barcode unique to each respondent. Spatial scan statistics and geographic information system tools were used to map hotspot areas of HIV prevalence. Bivariate and multivariable logistic regression models were used to identify social determinants of HIV infection.PopulationA total of 30 625 adults (16 515 women and 14 110 men) were included from 11 administrative states of Ethiopia.Main outcome measuresLaboratory-confirmed HIV serostatus is the main outcome variable.ResultsHIV prevalence reached 10–21% in the central, eastern and western geographic clusters of Ethiopia. Multivariable analysis showed that individuals who were in the middle, richer and richest wealth quintiles had increased odds of having HIV over those in the poorest quintile. Adults who had primary, secondary and higher educational levels had higher odds of being HIV positive than non-educated individuals. The odds of having HIV were higher among adults who had multiple lifetime sexual partners than those with a single partner. An increasing odds of HIV infection were observed among adults in the age groups of 25–29, 30–34, 35–39 and 40–45 years compared with adults in the age group of 45–49 years. Merchants had higher odds of being HIV positive than those who were not employed. The odds of having HIV were higher among urban residents and females than among rural residents and males, respectively.ConclusionsThis study found statistically significant HIV concentrations in administrative zones of central, eastern and western Ethiopia. Geospatial monitoring and targeting of prevention strategies for specific population groups is recommended.
Cross-sectional study of depression and help-seeking in Uttarakhand, North India
Authors: Mathias Kaaren , Goicolea Isabel , Kermode Michelle , Singh Lawrence , Shidhaye Rahul , Sebastian Miguel San 
Published: November 2015

ObjectivesThis study sought to use a population-based cross-sectional survey to describe depression prevalence, healthcare seeking and associations with socioeconomic determinants in a district in North India.SettingThis study was conducted in Sahaspur and Raipur, administrative blocks of Dehradun district, Uttarakhand, in July 2014.ParticipantsA population-based sample of 960 people over the age of 18 years was selected in 30 randomised clusters after being stratified by rural:urban census ratios.Primary outcome measuresThe survey used a validated screening tool, Patient Health Questionnaire, to identify people with depression, and collected information regarding socioeconomic variables and help-seeking behaviours. Depression prevalence and health seeking behaviours were calculated, and multivariable logistic regression was used to assess associations between risk factors and depression.ResultsPrevalence of depression was 6% (58/960), with a further 3.9% (37/960) describing a depressive episode of over 2 weeks in the past 12 months. Statistically significant adjusted OR for depression of more than 2 were found for people who were illiterate, classified as Scheduled Caste/Tribe or Other Backward Castes, living in temporary material housing and who had recently taken a loan. While over three quarters of people with depression (79%) had attended a private or government general medical practitioner in the past 3 months, none had received talking therapy (100% treatment gap) and two people (3.3%) had been prescribed antidepressants.ConclusionsThere are clear associations between social, educational and economic disadvantage and depression in this population. Strategies that address the social determinants of depression, such as education, social exclusion, financial protection and affordable housing for all are indicated. To address the large treatment gap in Uttarakhand, we must ensure access to primary and secondary mental health providers who can recognise and appropriately manage depression.
An embedded checklist in the Anesthesia Information Management System improves pre-anaesthetic induction setup: a randomised controlled trial in a simulation setting
Authors: Wetmore Douglas , Goldberg Andrew , Gandhi Nishant , Spivack John , McCormick Patrick , DeMaria Samuel 
Published: November 2015

BackgroundAnaesthesiologists work in a high stress, high consequence environment in which missed steps in preparation may lead to medical errors and potential patient harm. The pre-anaesthetic induction period has been identified as a time in which medical errors can occur. The Anesthesia Patient Safety Foundation has developed a Pre-Anesthetic Induction Patient Safety (PIPS) checklist. We conducted this study to test the effectiveness of this checklist, when embedded in our institutional Anesthesia Information Management System (AIMS), on resident performance in a simulated environment.MethodsUsing a randomised, controlled, observer-blinded design, we compared performance of anaesthesiology residents in a simulated operating room under production pressure using a checklist in completing a thorough pre-anaesthetic induction evaluation and setup with that of residents with no checklist. The checklist was embedded in the simulated operating room's electronic medical record.ResultsData for 38 anaesthesiology residents shows a statistically significant difference in performance in pre-anaesthetic setup and evaluation as scored by blinded raters (maximum score 22 points), with the checklist group performing better by 7.8 points (p<0.01). The effects of gender and year of residency on total score were not significant. Simulation duration (time to anaesthetic agent administration) was increased significantly by the use of the checklist.ConclusionRequired use of a pre-induction checklist improves anaesthesiology resident performance in a simulated environment. The PIPS checklist as an integrated part of a departmental AIMS warrant further investigation as a quality measure.