bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of sodium, deoxycorticosterone and duration of hypertension on pressor responses in rats
Authors: Bing Robert F. , Russell Gavin I. , Swales John D. , Thurston Herbert 
Published: December 2014

1. Enhanced pressor responsiveness to angiotensin II and noradrenaline has been demonstrated in the hypertension that follows deoxycorticosterone (DOC) and salt administration in the rat. The present studies were carried out to assess the importance of factors common to both pressor agents and those specific to individual agents such as receptor availability.2. Accordingly pressor reponses to angiotensin II and noradrenaline have been studied in normotensive salt‐loaded and sodium depleted rats with and without DOC, and in rats with DOC‐salt hypertension of short and long duration. These responses have been related to the plasma renin levels in the animals studied.3. Pressor reponses to angiotensin II were increased, dose‐response curve (d.r.c.) shifted to the left, in salt‐loaded rats and the administration of DOC produced a further increase. DOC‐salt hypertension of short duration was associated with an even greater responsiveness. Sodium depletion, however, reduced responsiveness (d.r.c. shifted to the right) and concurrent DOC administration did not alter this. Angiotensin II responses were closely correlated with plasma renin concentration over a wide range of values (p.r.c, r = ‐0·77, P < 0·001). The differences between the groups could be explained therefore by the number of unoccupied angiotensin II receptors available.4. On the other hand only sodium loaded rats that were also receiving DOC showed any change in noradrenaline responsiveness, when the dose‐response curve was shifted to the left. Noradrenaline responses showed no linear relationship to plasma renin concentration.5. The presence of hypertension did not significantly alter noradrenaline responses and the increase observed in angiotensin II responsiveness could be explained by the greater suppression of plasma renin in this group. Duration of hypertension had no effect on responsiveness to either agent.6. These results point to important differences in the pressor responsiveness to angiotensin II and noradrenaline with variation of salt intake and DOC administration.
Utility of Real-Time PCR for Detection of Exserohilum rostratum in Body and Tissue Fluids during the Multistate Outbreak of Fungal Meningitis and Other Infections
Authors: Gade Lalitha , Grgurich Dale E. , Kerkering Thomas M. , Brandt Mary E. , Litvintseva Anastasia P. 
Published: December 2014

ABSTRACT

Exserohilum rostratum
was the major cause of the multistate outbreak of fungal meningitis linked to contaminated injections of methylprednisolone acetate produced by the New England Compounding Center. Previously, we developed a fungal DNA extraction procedure and broad-range and
E. rostratum
-specific PCR assays and confirmed the presence of fungal DNA in 28% of the case patients. Here, we report the development and validation of a TaqMan real-time PCR assay for the detection of
E. rostratum
in body fluids, which we used to confirm infections in 57 additional case patients, bringing the total number of case patients with PCR results positive for
E. rostratum
to 171 (37% of the 461 case patients with available specimens). Compared to fungal culture and the previous PCR assays, this real-time PCR assay was more sensitive. Of the 139 identical specimens from case patients tested by all three methods, 19 (14%) were positive by culture, 41 (29%) were positive by the conventional PCR assay, and 65 (47%) were positive by the real-time PCR assay. We also compared the utility of the real-time PCR assay with that of the previously described beta-
d
-glucan (BDG) detection assay for monitoring response to treatment in case patients with serially collected CSF. Only the incident CSF specimens from most of the case patients were positive by real-time PCR, while most of the subsequently collected specimens were negative, confirming our previous observations that the BDG assay was more appropriate than the real-time PCR assay for monitoring the response to treatment. Our results also demonstrate that the real-time PCR assay is extremely susceptible to contamination and its results should be used only in conjunction with clinical and epidemiological data.
Sonication of Explanted Prosthesis Combined with Incubation in BD Bactec Bottles for Pathogen-Based Diagnosis of Prosthetic Joint Infection
Authors: Shen Hao , Tang Jin , Wang Qiaojie , Jiang Yao , Zhang Xianlong 
Published: December 2014

ABSTRACT

Prosthetic joint infection (PJI) is a rare but refractory complication of arthroplasty. Accurate identification of pathogens is a key step for successful treatment of PJI, which remains a challenge for clinicians and laboratory workers. We designed a combined culture method with sonication of implants and incubation in a BD Bactec system to improve the effectiveness of pathogen diagnosis in PJI. The aims of this study were to investigate the diagnostic accuracy of sonicate fluid cultures in the BD Bactec system and to compare the results with those of synovial fluid cultures in the BD Bactec system. The prosthetic components removed were sonicated in Ringer's solution, and then sonicate fluid was incubated in Bactec bottles for 5 days. Synovial fluid was incubated in Bactec bottles for 5 days as a control. Synovial fluid cultures with Bactec bottles and sonicate fluid cultures with Bactec bottles showed sensitivities of 64% and 88%, respectively (
P
= 0.009), with specificities of 98% and 87% (
P
= 0.032), respectively. Sonicate fluid cultures with Bactec bottles were more sensitive than synovial fluid cultures with Bactec bottles regardless of whether antimicrobial agents were used within 14 days before surgery (81% versus 52%;
P
= 0.031) or not (93% versus 72%;
P
= 0.031). Sonication of explanted prostheses followed by incubation of the resulting sonicate fluid in Bactec bottles detected many more pathogens than did synovial fluid cultures with Bactec bottles. This method is also effective in cases with antibiotic treatment before surgery.
Clinical and Microbiological Characteristics of Eggerthella lenta Bacteremia
Authors: Gardiner B. J. , Tai A. Y. , Kotsanas D. , Francis M. J. , Roberts S. A. , Ballard S. A. , Junckerstorff R. K. , Korman T. M. 
Published: December 2014

ABSTRACT

Eggerthella lenta
is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with
E. lenta
bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as
E. lenta
by both commercially available matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a
vanA
or
vanB
gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.
Rapid Homogeneous Immunoassay Based on Time-Resolved Förster Resonance Energy Transfer for Serodiagnosis of Acute Hantavirus Infection
Authors: Hepojoki Satu , Hepojoki Jussi , Hedman Klaus , Vapalahti Olli , Vaheri Antti 
Published: December 2014

ABSTRACT

We recently introduced a homogeneous immunoassay based on time-resolved Förster resonance energy transfer (TR-FRET) elicited by fluorophore-labeled antigen and fluorophore-labeled protein L, bound by an immunoglobulin. As the first clinical application, we employ this approach (LFRET) in serodiagnosis of Puumala hantavirus (PUUV) infection. A reference panel containing serum from individuals with acute (
n =
21) or past (
n =
17) PUUV infection and from PUUV-seronegative individuals (
n =
20) was used to define the parameters. The clinical assay performance was evaluated with a prospectively collected serum panel (panel 2;
n =
153). Based on the results for panel 1, the threshold for positivity was set at a signal level that was 3-fold over background, while those with a signal <3-fold over the background level were considered PUUV seronegative. With panel 1, 20/21 acute- and 7/10 past-infection samples induced positive signals, compared to 0/20 seronegatives. With panel 2, a positive signal was obtained in 39/40 acute- and 4/10 past-infection samples, as opposed to 7/103 seronegatives. However, after IgG depletion, 58/61 acute-infection samples were LFRET positive, while all past-infection and seronegative samples were negative, corresponding to 100% specificity and 95% sensitivity in detection of acute PUUV infection. We demonstrate that the novel immunoassay is a promising tool for rapid serodiagnosis of acute Puumala virus infection.
Contribution of (1,3)-Beta-
d
-Glucan to Diagnosis of Invasive Candidiasis after Liver Transplantation
Authors: Levesque E. , El Anbassi S. , Sitterle E. , Foulet F. , Merle J. C. , Botterel F. 
Published: December 2014

ABSTRACT

Invasive candidiasis (IC) causes high morbidity and mortality rates after liver transplantation, in part due to delayed diagnosis. The fungal cell wall component (1,3)-beta-
d
-glucan (BG) could be an early biomarker of IC. This preliminary prospective study was designed to evaluate the contribution of BG measurements to the diagnosis of IC after liver transplantation. All consecutive patients who underwent liver transplantation at Henri Mondor Hospital in France between January and June 2013 were enrolled prospectively in the study. They were monitored weekly for colonization by
Candida
, and colonization index values were calculated. Serum samples were tested for BG (Fungitell; Cape Cod Inc.) at least weekly between liver transplantation and discharge from the hospital. A total of 52 patients (including 39 male patients) were enrolled, with a median age of 55 years (range, 31 to 69 years). The median Model for End-Stage Liver Disease (MELD) score was 27 (range, 6 to 40). Cultures from 42 patients (81%) yielded
Candida
spp., with the most common
Candida
species isolated being
Candida glabrata
(47%). Six cases of documented IC were found for four of the 52 patients. On the day the clinical diagnosis of IC was made, analysis based on combining two sequential BG-positive samples (>146 pg/ml) and a colonization index of ≥0.5 revealed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) results of 83%, 89%, 50%, and 97.6%, respectively. The detection of BG associated with
Candida
colonization may be a promising tool based on a high NPV that can rule out IC among high-risk patients.
Evaluation of the Cepheid Xpert C. difficile/
Epi
and Meridian Bioscience
illumi
gene C. difficile Assays for Detecting Clostridium difficile Ribotype 033 Strains
Authors: Androga Grace O. , McGovern Alan M. , Elliott Briony , Chang Barbara J. , Perkins Timothy T. , Foster Niki F. , Riley Thomas V. 
Published: December 2014

ABSTRACT

Clostridium difficile
PCR ribotype 033 (RT033) is found in the gastrointestinal tracts of production animals and, occasionally, humans. The
illumi
gene
C. difficile
assay (Meridian Bioscience, Inc.) failed to detect any of 52
C. difficile
RT033 isolates, while all strains signaled positive for the binary toxin genes but were reported as negative for
C. difficile
by the Xpert
C. difficile
/
Epi
assay (Cepheid).
LMP1 Promotes Expression of Insulin-Like Growth Factor 1 (IGF1) To Selectively Activate IGF1 Receptor and Drive Cell Proliferation
Authors: Tworkoski Kathryn , Raab-Traub Nancy 
Published: December 2014

ABSTRACT
Epstein-Barr Virus (EBV) is a gammaherpesvirus that infects the majority of the human population and is linked to the development of multiple cancers, including nasopharyngeal carcinoma. Latent membrane protein 1 (LMP1) is considered the primary oncoprotein of EBV, and in epithelial cells it induces the expression and activation, or phosphorylation, of the epidermal growth factor receptor kinase. To identify effects on additional kinases, an unbiased screen of receptor tyrosine kinases potentially activated by LMP1 was performed. Using a protein array, it was determined that LMP1 selectively activates insulin-like growth factor 1 receptor (IGF1R). This activation takes place in fibroblast, epithelial, and nasopharyngeal cell lines that express LMP1 stably and transiently. Of note, LMP1 altered the phosphorylation, but not the expression, of IGF1R. The use of LMP1 mutants with defective signaling domains revealed that the C-terminal activating region 2 domain of LMP1 increased the mRNA expression and the secretion of the ligand IGF1, which promoted phosphorylation of IGF1R. IGF1R phosphorylation was dependent upon activation of canonical NF-κB signaling and was suppressed by IκBα and a dominant negative form of TRAF6. Inhibition of IGF1R activation with two small-molecule inhibitors, AG1024 and picropodophyllin (PPP), or with short hairpin RNA (shRNA) directed against IGF1R selectively reduced proliferation, focus formation, and Akt activation in LMP1-positive cells but did not impair LMP1-induced cell migration. Expression of constitutively active Akt rescued cell proliferation in the presence of IGF1R inhibitors. These findings suggest that LMP1-mediated activation of IGF1R contributes to the ability of LMP1 to transform epithelial cells.

IMPORTANCE
EBV is linked to the development of multiple cancers in both lymphoid and epithelial cells, including nasopharyngeal carcinoma. Nasopharyngeal carcinoma is a major cancer that develops in specific populations, with nearly 80,000 new cases reported annually. LMP1 is consistently expressed in early lesions and continues to be detected within 50 to 80% of these cancers at later stages. It is therefore of paramount importance to understand the mechanisms through which LMP1 alters cell growth and contributes to tumorigenesis. This study is the first to determine that LMP1 activates the IGF1R tyrosine kinase by regulating expression of the ligand IGF1. Additionally, the data in this paper reveal that specific targeting of IGF1R selectively impacts LMP1-positive cells. These findings suggest that therapies directed against IGF1R may specifically impair the growth of EBV-infected cells.
Improving Neutralization Potency and Breadth by Combining Broadly Reactive HIV-1 Antibodies Targeting Major Neutralization Epitopes
Authors: Kong Rui , Louder Mark K. , Wagh Kshitij , Bailer Robert T. , deCamp Allan , Greene Kelli , Gao Hongmei , Taft Justin D. , Gazumyan Anna , Liu Cassie , Nussenzweig Michel C. , Korber Bette , Montefiori David C. , Mascola John R. 
Published: December 2014

ABSTRACT

The isolation of broadly neutralizing HIV-1 monoclonal antibodies (MAbs) to distinct epitopes on the viral envelope glycoprotein (Env) provides the potential to use combinations of MAbs for prevention and treatment of HIV-1 infection. Since many of these MAbs have been isolated in the last few years, the potency and breadth of MAb combinations have not been well characterized. In two parallel experiments, we examined the
in vitro
neutralizing activities of double-, triple-, and quadruple-MAb combinations targeting four distinct epitopes, including the CD4-binding site, the V1V2-glycan region, the V3-glycan supersite, and the gp41 membrane-proximal external region (MPER), using a panel of 125 Env-pseudotyped viruses. All MAb combinations showed substantially improved neutralization breadth compared to the corresponding single MAbs, while the neutralization potency of individual MAbs was maintained. At a 50% inhibitory concentration (IC
50
) cutoff of 1 μg/ml per antibody, double-MAb combinations neutralized 89 to 98% of viruses, and triple combinations neutralized 98 to 100%. Overall, the improvement of neutralization breadth was closely predicted by an additive-effect model and explained by complementary neutralization profiles of antibodies recognizing distinct epitopes. Subtle but consistent favorable interactions were observed in some MAb combinations, whereas less favorable interactions were observed on a small subset of viruses that are highly sensitive to V3-glycan MAbs. These data demonstrate favorable
in vitro
combinations of broadly neutralizing HIV-1 MAbs and suggest that such combinations could have utility for HIV-1 prevention and treatment.

IMPORTANCE
Over the last 5 years, numerous broadly reactive HIV-1-neutralizing MAbs have been isolated from B cells of HIV-1-infected donors. Each of these MAbs binds to one of the major vulnerable sites (epitopes) on the surface of the viral envelope glycoprotein. Since antibodies to distinct viral epitopes could theoretically act together to provide greater potency and breadth of virus neutralization, we tested physical mixtures of double, triple, and quadruple combinations of neutralizing MAbs targeting four major epitopes on HIV-1 Env. When tested together, antibody combinations showed substantially improved neutralization breadth compared to single MAbs. This improvement could be explained by the complementary neutralization profiles of individual MAbs. We further demonstrated that each antibody maintained its full neutralization potency when used in combination with other MAbs. These data provide a rationale for clinical use of antibody-based combinations for HIV-1 prevention and therapy.
A population-based study of premature mortality in relation to neighbourhood density of alcohol sales and cheque cashing outlets in Toronto, Canada
Authors: Matheson Flora I , Creatore Maria Isabella , Gozdyra Piotr , Park Alison L , Ray Joel G 
Published: December 2014

ObjectiveAlcohol overuse and poverty, each associated with premature death, often exist within disadvantaged neighbourhoods. Cheque cashing places (CCPs) may be opportunistically placed in disadvantaged neighbourhoods, where customers abound. We explored whether neighbourhood density of CCPs and alcohol outlets are each related to premature mortality among adults.DesignRetrospective population-based study.Setting140 neighbourhoods in Toronto, Ontario, 2005–2009.ParticipantsAdults aged 20–59 years.MeasuresOur primary outcome was premature all-cause mortality among adults aged 20–59 years. Across neighbourhoods we explored neighbourhood density, in km2, of CCPs and alcohol outlets, and the relation of each to premature mortality. Poisson regression provided adjusted relative risks (aRRs) and 95% CIs, adjusting for material deprivation quintile (Q), crime Q and number of banks.ResultsIntentional self-harm, accidental poisoning and liver disease were among the top five causes of premature death among males aged 20–59 years. The overall premature mortality rate was 96.3/10 000 males and 55.9/10 000 females. Comparing the highest versus lowest CCP density Q, the aRR for death was 1.25 (95% CI 1.15 to 1.36) among males and 1.11 (95% CI 0.99 to 1.24) among females. The corresponding aRR comparing the highest Q versus lowest Q alcohol outlet density in relation to premature mortality was 1.36 (95% CI 1.25 to 1.48) for males and 1.11 (95% CI 1.00 to 1.24) for females. The pattern of the relation between either CCPs or alcohol outlet density and premature mortality was typically J shaped.ConclusionsThere is a J-shaped relation between CCP or alcohol outlet density and premature mortality, even on controlling for conventional measures of poverty. Formal banking and alcohol reduction strategies might be added to health promotion policies aimed at reducing premature mortality in highly affected neighbourhoods.
LIGHT MESON STUDIES WITH WASA-AT-COSY
Authors: HEIJKENSKJÖLD L. ,   for the WASA-at-COSY collaboration
Published: December 2014

Detailed experimental studies of the decays and interactions of light mesons, such as π0, η and ω, are highly needed as precision tests for theoretical models. The Wide Angle Shower Apparatus (WASA) detector is one of the available experimental set-ups optimized for studying production and decays of light mesons. In contrast to the focus of this workshop, the mesons are produced through proton-proton or proton-deuteron collisions using a fixed target. This paper will present status of studies performed by the WASA-at-COSY collaboration in the field of light meson interactions.
Modelling fluid flow in Opalinus Clay excavation damage zone. A semi-analytical approach
Authors: Alcoverro J. , Olivella S. , Alonso E. E. 
Published: December 2014

Abstract

The HG-A
in situ test
, located at the Mont Terri Underground Rock Laboratory (URL), was analysed as part of the FORGE project. This test investigated the behaviour of the excavation damage zone (EDZ) around a backfilled microtunnel by a series of water- and gas-injection tests. Prior to testing, the backfilled microtunnel was sealed with a hydraulic megapacker system. A key aspect was the investigation of crack opening and closure along the EDZ in response to water and gas injections in the context of radioactive waste disposal. In the model, the intrinsic permeability of the EDZ was assumed to depend on deformation, and additional simplifying assumptions were considered: axisymmetry about the tunnel axis; no gravity; soil slices orthogonal to the tunnel axis move independently and in plane strain; liquid and gas flows along the EDZ parallel to the tunnel axis; and undrained saturated conditions for the Opalinus Clay. As a result, the field equations were reduced to differential equations for liquid and gas pressures defined in a one-dimensional (1D) domain representing the EDZ. The main trends of the pressure evolution observed in the test section were reproduced. A 2D axisymmetric model confirmed the validity of the simplifying assumptions, except for small zones of the EDZ near the megapacker ends.