bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poly-
N
-Acetylglucosamine Expression by Wild-Type Yersinia pestis Is Maximal at Mammalian, Not Flea, Temperatures
Authors: Yoong Pauline , Cywes-Bentley Colette , Pier Gerald B. 
Published: August 2012

ABSTRACT

Numerous bacteria, including
Yersinia pestis
, express the poly-
N
-acetylglucosamine (PNAG) surface carbohydrate, a major component of biofilms often associated with a specific appearance of colonies on Congo red agar. Biofilm formation and PNAG synthesis by
Y. pestis
have been reported to be maximal at 21 to 28°C or “flea temperatures,” facilitating the regurgitation of
Y. pestis
into a mammalian host during feeding, but production is diminished at 37°C and thus presumed to be decreased during mammalian infection. Most studies of PNAG expression and biofilm formation by
Y. pestis
have used a low-virulence derivative of strain KIM, designated KIM6+, that lacks the pCD1 virulence plasmid, and an isogenic mutant without the pigmentation locus, which contains the hemin storage genes that encode PNAG biosynthetic proteins. Using confocal microscopy, fluorescence-activated cell sorter analysis and growth on Congo red agar, we confirmed prior findings regarding PNAG production with the KIM6+ strain. However, we found that fully virulent wild-type (WT) strains KIM and CO92 had maximal PNAG expression at 37°C, with lower PNAG production at 28°C both in broth medium and on Congo red agar plates. Notably, the typical dark colony morphology appearing on Congo red agar was maintained at 28°C, indicating that this phenotype is not associated with PNAG expression in WT
Y. pestis
. Extracts of WT sylvatic
Y. pestis
strains from the Russian Federation confirmed the maximal expression of PNAG at 37°C. PNAG production by WT
Y. pestis
is maximal at mammalian and not insect vector temperatures, suggesting that this factor may have a role during mammalian infection.

IMPORTANCE
Yersinia pestis
transitions from low-temperature residence and replication in insect vectors to higher-temperature replication in mammalian hosts. Prior findings based primarily on an avirulent derivative of WT (wild-type) KIM, named KIM6+, showed that biofilm formation associated with synthesis of poly-
N
-acetylglucosamine (PNAG) is maximal at 21 to 28°C and decreased at 37°C. Biofilm formation was purported to facilitate the transmission of
Y. pestis
from fleas to mammals while having little importance in mammalian infection. Here we found that for WT strains KIM and CO92, maximal PNAG production occurs at 37°C, indicating that temperature regulation of PNAG production in WT
Y. pestis
is not mimicked by strain KIM6+. Additionally, we found that Congo red binding does not always correlate with PNAG production, despite its widespread use as an indicator of biofilm production. Taken together, the findings show that a role for PNAG in WT
Y. pestis
infection should not be disregarded and warrants further study.
Salmonella
“Sops” Up a Preferred Electron Receptor in the Inflamed Intestine
Authors: Bliska James B. , van der Velden Adrianus W. M. 
Published: August 2012

ABSTRACT

The microbiota of the mammalian intestinal tract represents a formidable barrier to colonization by pathogens. To overcome this resistance to colonization, bacterial pathogens use virulence factors to induce intestinal inflammation, which liberates nutrients for selective use by the infecting microbe. Studies of
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) infection in a streptomycin-treated mouse colitis model show how virulence factor-induced inflammation can produce nutrients used selectively by the pathogen. Type III secreted effectors of invading
S
. Typhimurium induce inflammation in the intestine (epithelial cells and lamina propria macrophages) that causes changes in the composition of the lumen. For example, neutrophils entering the intestine produce superoxide, resulting in production of tetrathionate, which
S
. Typhimurium in the lumen uses as an electron acceptor for anaerobic respiration. In their recent study, Lopez et al. demonstrate that
S
. Typhimurium strains that are lysogenized with a phage encoding type III effector SopE induce the host to produce nitric oxide synthetase (iNOS) in the intestine (C. A. Lopez et al., mBio 3:e00143-12, 2012). Nitric oxide is converted to a highly favorable electron acceptor, nitrate. As a result, growth of
sopE
+
S
. Typhimurium in the intestine lumen is boosted by nitrate respiration. This is a striking example of how acquisition of a virulence factor by horizontal gene transfer can increase the metabolic fitness of a pathogen. Interestingly, survival of the invading bacteria is probably decreased as a result of the SopE-induced immune response, and yet the
S
. Typhimurium bacteria that multiply in the lumen of the intestine can efficiently disseminate to another host, ensuring success for the pathogen.
A 24-h helpline for access to expert management advice for food allergy-related anaphylaxis in children: protocol for a pragmatic randomised controlled trial
Authors: Kelleher Maeve M , Hourihane Jonathan O'B , DunnGalvin Audrey , Cullinane Claire , Fitzsimons John , Sheikh Aziz 
Published: August 2012

ObjectivesAnaphylaxis is an important, potentially life-threatening paediatric emergency. It is responsible for considerable morbidity and, in some cases, death. Poor outcomes may be associated with an inability to differentiate between milder and potentially more severe reactions and an associated reluctance to administer self-injectable adrenaline. This study aims to assess the effectiveness of a 24-h telephone access to specialist paediatric allergy expert advice in improving the quality of life of children and their families with potentially life-threatening food allergy (ie, anaphylaxis) compared with usual clinical care.Methods and analysisChildren aged less than 16 years with food allergy and who carry an adrenaline autoinjector will be recruited from the Paediatric Allergy Clinic at Cork University Hospital, Ireland and baseline disease-specific quality of life will be ascertained using the validated Food Allergy Quality of Life Questionnaire (FAQLQ). Participants will be randomised for a period of 6 months to the 24-h telephone specialist support line or usual care. The primary outcome measure of interest is a change in FAQLQ scores, which will be assessed at 0, 1 and 6 months postrandomisation. Analysis will be on an intention-to-treat basis using a 2×3 repeated measures within-between analysis of variance. Although lacking power, we will in addition assess the impact of the intervention on a range of relevant process and clinical endpoints.Ethics and disseminationThis trial protocol has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The findings will be presented at international scientific conferences and will be reported on in the peer-reviewed literature in early 2013.
Longitudinal cohort protocol study of oropharyngeal dysphagia: relationships to gross motor attainment, growth and nutritional status in preschool children with cerebral palsy
Authors: Benfer Katherine A , Weir Kelly A , Bell Kristie L , Ware Robert S , Davies Peter S W , Boyd Roslyn N 
Published: August 2012

IntroductionThe prevalence of oropharyngeal dysphagia (OPD) in children with cerebral palsy (CP) is estimated to be between 19% and 99%. OPD can impact on children's growth, nutrition and overall health. Despite the growing recognition of the extent and significance of health issues relating to OPD in children with CP, lack of knowledge of its profile in this subpopulation remains. This study aims to investigate the relationship between OPD, attainment of gross motor skills, growth and nutritional status in young children with CP at and between two crucial age points, 18–24 and 36 months, corrected age.Methods and analysisThis prospective longitudinal population-based study aims to recruit a total of 200 children with CP born in Queensland, Australia between 1 September 2006 and 31 December 2009 (60 per birth-year). Outcomes include clinically assessed OPD (Schedule for Oral Motor Assessment, Dysphagia Disorders Survey, Pre-Speech Assessment Scale, signs suggestive of pharyngeal phase impairment, Thomas-Stonell and Greenberg Saliva Severity Scale), parent-reported OPD on a feeding questionnaire, gross motor skills (Gross Motor Function Measure, Gross Motor Function Classification System and motor type), growth and nutritional status (linear growth and body composition) and dietary intake (3 day food record). The strength of relationship between outcome and exposure variables will be analysed using regression modelling with ORs and relative risk ratios.Ethics and disseminationThis protocol describes a study that provides the first large population-based study of OPD in a representative sample of preschool children with CP, using direct clinical assessment. Ethics has been obtained through the University of Queensland Medical Research Ethics Committee, the Children's Health Services District Ethics Committee, and at other regional and organisational ethics committees. Results are planned to be disseminated in six papers submitted to peer reviewed journals, and presentations at relevant international conferences.
Morphological study of synovial changes in two-stage reconstructions of the infected hip and knee arthroplasties
Authors: Gontarewicz Arthur , Niggemeyer Oliver , Tharun Lars , Grancicova Livia , Rüther Wolfgang , Zustin Jozef 
Published: August 2012

ObjectivesTo study the morphological changes of the regenerating synovium in two-stage revision arthroplasty, which is the gold standard for treatment of periprosthetic joint infection.DesignThe authors analysed a series of synovial biopsies to examine morphological changes in healing periprosthetic tissues damaged by previous surgery and infection.MethodsSynovial tissues from 19 patients (10 knees and 9 hips) who underwent a two-stage exchange surgery for periprosthetic infection were reviewed and correlated with clinical and laboratory findings.SettingRetrospective morphological study.ParticipantsArchival tissues from 19 two-stage revision arthroplasties in adult patients.ResultsHealing synovial tissue obtained at the reimplantation surgery showed characteristic layering: superficial fibrin exudate, immature richly vascularised granulation tissue and deeper maturing granulation tissue and fibrosis. Although increased neutrophil counts were found in the majority of cases, 2 of 19 cases showed dense infiltrates indicative of persistent infection, which correlated with positive microbiology in one case. One of the cases failed due to acetabular loosening and two cases failed due to late superinfection. One case showed a dense infiltration of eosinophils suggestive of a hypersensitivity reaction, which was subsequently proven by cutaneous tests. Foci of extramedullary haematopoiesis were detected in two cases.ConclusionsWe observed characteristic morphological changes in the healing synovial tissue during reimplantation surgery for periprosthetic infection in serologically and microbiologically sterile tissues. Substantial increased counts of synovial neutrophils (>200 cells/10 high-power fields) seem to be indicative of persistent infection of the joint; therefore, prolonged antibiotic therapy should be considered in positive cases.
De novo pseudoaneurysm formation after angioplasty and stenting of posterior circulation intracranial atherosclerotic disease: mechanism, characterization with intravascular ultrasound and management considerations
Authors: Dabus Guilherme , Linfante Italo , Samaniego Edgar A 
Published: August 2012

BackgroundThe formation of de novo pseudoaneurysms after stent implantation has not been well characterized after stenting of intracranial vessels. Its clinical significance is unknown, resulting in a difficult decision making process with regard to its treatment.MethodsThe database of patients treated at the Baptist Cardiac and Vascular Institute, Miami, Florida, was reviewed. All patients with symptomatic intracranial atherosclerotic disease (ICAD) who underwent angioplasty and stenting with the Gateway-Wingspan system under the Food and Drug Administration Humanitarian Device Exemption protocol and had subsequent follow-up imaging demonstrating de novo pseudoaneurysm formation after stent implantation were included.Results21 patients with symptomatic ICAD who underwent angioplasty and stenting had follow-up angiography performed. Of these, we identified three patients (14%) who had de novo pseudoaneurysm formation in the follow-up angiography. All three patients were men in their sixties. All of our patients were asymptomatic and the lesions were found on routine follow-up angiography. No intervention was performed. One patient underwent intravascular ultrasound for better characterization of the lesion. Two lesions had either resolved or decreased in size on follow-up angiography. The other lesion remained stable.ConclusionsPost stenting pseudoaneurysm formation is a possible complication after intracranial stenting with unknown clinical significance. Our small series suggest that these cases may be managed conservatively.
Telephone referrals by junior doctors: a randomised controlled trial assessing the impact of SBAR in a simulated setting
Authors: Cunningham Neil James , Weiland Tracey J , van Dijk Julian , Paddle Paul , Shilkofski Nicole , Cunningham Nicola Yumei 
Published: August 2012

Abstract

Objective
To determine whether exposing junior doctors to Situation, Background, Assessment, Recommendation (SBAR) improves their telephone referrals. SBAR is a standardised minimum information communication tool.

Methods
A randomised controlled trial with participants and rating clinicians both blinded to group allocation. Hospital interns from a 2-year period (2006–2007) participated in two simulated clinical scenarios which required them to make telephone referrals. The intervention group was educated in SBAR between scenarios. Pre and post intervention telephone referrals were recorded, scored and compared. Six-month follow-up and year group comparisons were also made. An objective rating score measured the presence of specific ‘critical data’ communication elements on a scale of 1–12. Qualitative measures of global rating scores and participant self-rated scoring of performance were recorded. Time to ‘first pitch’ (the intern's initial speech) was also recorded.

Results
Data were available for 66 interns out of 91 eligible. SBAR exposure did not increase the number of communication elements presented; objective rating scores were 8.5 (IQ 7.0–9.0) for SBAR and 8.0 (IQ 6.5–8.0) for the control group (p=0.051). Median global rating scores, designed to measure ‘call impact’, were higher following SBAR exposure (SBAR: 3.0 (IQR 2.0–4.0); control: 2.0 (IQ 1.0–3.0); p=0.003)). Global rating scores improved as time to ‘first pitch’ duration decreased (p=0.001). SBAR exposure did not improve time to ‘first pitch’ duration.

Conclusion
In this simulated setting exposure to SBAR did not improve telephone referral performance by increasing the amount of critical information presented, despite the fact that it is a minimum data element tool. SBAR did improve the ‘call impact’ of the telephone referral as measured by qualitative global rating scores.
Magnetostratigraphy susceptibility for the Guadalupian series GSSPs (Middle Permian) in Guadalupe Mountains National Park and adjacent areas in West Texas
Authors: Ellwood Brooks B. , Lambert Lance L. , Tomkin Jonathan H. , Bell Gorden L. , Nestell Merlynd K. , Nestell Galina P. , Wardlaw Bruce R. 
Published: August 2012

Abstract
Here we establish a magnetostratigraphy susceptibility zonation for the three Middle Permian Global boundary Stratotype Sections and Points (GSSPs) that have recently been defined, located in Guadalupe Mountains National Park, West Texas, USA. These GSSPs, all within the Middle Permian Guadalupian Series, define (1) the base of the Roadian Stage (base of the Guadalupian Series), (2) the base of the Wordian Stage and (3) the base of the Capitanian Stage. Data from two additional stratigraphic successions in the region, equivalent in age to the Kungurian–Roadian and Wordian–Capitanian boundary intervals, are also reported. Based on low-field, mass specific magnetic susceptibility (χ) measurements of 706 closely spaced samples from these stratigraphic sections and time-series analysis of one of these sections, we (1) define the magnetostratigraphy susceptibility zonation for the three Guadalupian Series Global boundary Stratotype Sections and Points; (2) demonstrate that χ datasets provide a proxy for climate cyclicity; (3) give quantitative estimates of the time it took for some of these sediments to accumulate; (4) give the rates at which sediments were accumulated; (5) allow more precise correlation to equivalent sections in the region; (6) identify anomalous stratigraphic horizons; and (7) give estimates for timing and duration of geological events within sections.
The Pancreas Cancer Microenvironment
Authors: Feig Christine , Gopinathan Aarthi , Neesse Albrecht , Chan Derek S. , Cook Natalie , Tuveson David A. 
Published: August 2012

Abstract
Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients. Clin Cancer Res; 18(16); 4266–76. ©2012 AACR.
A Phase I Dose-Finding Trial of Recombinant Interleukin-21 and Rituximab in Relapsed and Refractory Low Grade B-cell Lymphoproliferative Disorders
Authors: Timmerman John M. , Byrd John C. , Andorsky David J. , Yamada Reiko E. , Kramer Janet , Muthusamy Natarajan , Hunder Naomi , Pagel John M. 
Published: August 2012

AbstractPurpose: We conducted a phase I study to determine the safety, maximum-tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies.Experimental Design: One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy.Results: Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months).Conclusions: Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted. Clin Cancer Res; 18(20); 5752–60. ©2012 AACR.
Macrophages Promote Fibroblast Growth Factor Receptor-Driven Tumor Cell Migration and Invasion in a Cxcr2-Dependent Manner
Authors: Bohrer Laura R. , Schwertfeger Kathryn L. 
Published: August 2012

Abstract
Infiltration of immune cells, specifically macrophages, into the tumor microenvironment has been linked to increased mammary tumor formation and progression. Activation of growth factor receptor signaling pathways within mammary epithelial cells, such as the fibroblast growth factor receptor 1 (FGFR1) pathway, induces recruitment of macrophages to the mammary epithelium. These macrophages promote increased epithelial cell proliferation and angiogenesis. However, the specific mechanisms by which these macrophages are regulated by the preneoplastic epithelial cells and the mechanisms of action of the macrophages within the developing FGFR1-driven tumor microenvironment remain unknown. In this study, we show that activation of inducible FGFR1 in mammary glands leads to decreased activity of the TGFβ/Smad3 pathway in macrophages associated with early stage lesions. Further studies show that macrophages have increased expression of inflammatory chemokines that bind Cxcr2 following exposure to conditioned media from mammary epithelial and tumor cells in which the FGF pathway had been activated. The increase in these ligands is inhibited following activation of the TGFβ pathway, suggesting that decreased TGFβ signaling contributes to the upregulation of these chemokines. Using coculture studies, we further show that macrophages are capable of promoting epithelial and tumor cell migration and invasion through activation of Cxcr2. These results indicate that macrophage-derived Cxcr2 ligands may be important for promoting mammary tumor formation regulated by FGFR signaling. Furthermore, these results suggest that targeting Cxcr2 may represent a novel therapeutic strategy for breast cancers that are associated with high levels of infiltrating macrophages. Mol Cancer Res; 10(10); 1294–305. ©2012 AACR.
ABO Blood Group and Risk of Coronary Heart Disease in Two Prospective Cohort Studies
Authors: He Meian , Wolpin Brian , Rexrode Kathy , Manson JoAnn E. , Rimm Eric , Hu Frank B. , Qi Lu 
Published: August 2012

Objective—
Epidemiological data regarding the association between ABO blood groups and risk of coronary heart disease (CHD) have been inconsistent. We sought to investigate the associations between ABO blood group and CHD risk in prospective cohort studies.

Methods and Results—

Two large, prospective cohort studies (the Nurses’ Health Study [NHS] including 62 073 women and the Health Professionals Follow-up Study [HPFS] including 27 428 men) were conducted with more than 20 years of follow-up (26 years in NHS and 24 years in HPFS). A meta-analysis was performed to summarize the associations from the present study and previous studies. In NHS, during 1 567 144 person-years of follow-up, 2055 participants developed CHD; in HPFS, 2015 participants developed CHD during 517 312 person-years of follow-up. ABO blood group was significantly associated with the risk of developing CHD in both women and men (log-rank test;
P
=0.0048 and 0.0002, respectively). In the combined analysis adjusted for cardiovascular risk factors, compared with participants with blood group O, those with blood groups A, B, or AB were more likely to develop CHD (adjusted hazard ratios [95% CI] for incident CHD were 1.06 [0.99–1.15], 1.15 [1.04–1.26], and 1.23 [1.11–1.36], respectively). Overall, 6.27% of the CHD cases were attributable to inheriting a non-O blood group. Meta-analysis indicated that non-O blood group had higher risk of CHD (relative risk =1.11; 95% CI, 1.05–1.18;
P
=0.001) compared with O blood group.

Conclusion—
These data suggest that ABO blood group is significantly associated with CHD risk. Compared with other blood groups, those with the blood type O have moderately lower risk of developing CHD.