bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional gastrointestinal transit times in severe ulcerative colitis
Authors: Haase A. M. , Gregersen T. , Christensen L. A. , Agnholt J. , Dahlerup J. F. , Schlageter V. , Krogh K. 
Published: January 2016

AbstractBackgroundGastrointestinal (GI) dysmotility may present secondary to inflammatory bowel disease. The main aim of this study was to investigate GI motility in ulcerative colitis (UC) patients during severe disease activity.MethodsTwenty patients with severe UC were studied with a novel telemetric capsule system (3D‐Transit) designed for minimally invasive, ambulatory assessment of total and regional GI transit times. Ten patients were available for follow‐up during remission. Data were compared to those of 20 healthy subjects (HS).Key ResultsTotal GI transit time was significantly longer in patients with severe UC (median 44.5 h [range 9.9–102.7 h]) than in HS (median 27.6 h [range 9.6–56.4 h]) (p = 0.032). Additionally, during severe UC, transit time was prolonged through the proximal colon (p = 0.003) and there were strong trends toward longer than normal small intestinal transit time (HS: median 4.9 h [range 3.4–8.3 h] vs severe UC patients: median 5.9 h [range 3.9–11.9 h]; p = 0.053) and colorectal transit times (HS: median 18.2 h [range 1.5–43.7] vs severe UC patients: median 34.9 h [range 0.4–90.9 h]; p = 0.056). Our data further indicate that total GI and colorectal transit times may be prolonged in UC during early remission.Conclusions & InferencesTotal GI transit times are significantly prolonged during severe UC.
Antibody profiling in ultrasound normal individuals with positive serology for cystic echinococcosis
Authors: Mourglia‐Ettlin G. , Miles S. , Hernández A. , Dematteis S. 
Published: January 2016

SummaryCystic echinococcosis is a zoonotic disease caused by the cestode parasite Echinococcus granulosus. In endemic regions, seropositive individuals to E. granulosus usually and markedly outnumber image‐confirmed cases of cystic echinococcosis, suggesting that some parasite challenges derive in unsuccessful infection establishments. However, it is still unknown whether such parasite‐specific antibodies in healthy individuals might play a role in resistance/susceptibility to the infection. Therefore, we have here analysed the profile of antibodies recognizing E. granulosus antigens in seropositive but ultrasound normal individuals, as well as in surgery‐confirmed patients and healthy donors. Our results showed that ultrasound normal individuals exhibited low avidity IgG antibodies, as well as low levels of parasite‐specific IgG1 and IgG4 antibodies. In addition, they displayed significant levels of specific IgE, and thus, they revealed a uniquely high IgE:IgG4 ratio. Moreover, high levels of parasite‐specific IgM were detected in such individuals, which showed characteristics of natural cross‐reacting antibodies. Therefore, our results indicate that ultrasound normal individuals but seropositive for E. granulosus antigens exhibit a distinctive antibody profile. In this regard, possible associations between their antiparasite antibodies and potential resistance mechanisms to cystic echinococcosis are discussed.
Policy Change, Policy Feedback, and Interest Mobilization: The Politics of Nuclear Waste Management
Authors: Nowlin Matthew C. 
Published: January 2016

AbstractMany of the leading theories of the policy process are aimed at providing insights into the factors that make policy change more (or less) likely. In general, policy change is seen as a result of shifting dynamics within policy subsystems. However, building on theories of policy feedback and interest mobilization, this article examines whether policy change, apart from being an effect of subsystem dynamics, can be a cause of shifting dynamics as latent actors are motivated to participate in the subsystem as a result of policy change. Two hypotheses regarding post‐policy change mobilization are developed and tested using data on participation in congressional hearings concerning the management of nuclear waste. The findings suggest that policy change can activate latent policy actors, specifically those actors that view themselves as “losing” as a result of the policy change. These results point to the need for scholars to examine the potential impacts of post‐policy change dynamics on policy development.
The Outsourcing of Research and Development in Global Markets: Evidence from France
Authors: Jabbour Liza , Zuniga Pluvia 
Published: January 2016

AbstractThe pace of technological change, the increasing need for multidisciplinary competences and the rising costs of innovation have contributed to the global expansion of technological activities, including the international outsourcing of research and development (R&D). This paper shows that firms involved in international outsourcing of R&D are of a particular kind: they are highly outward oriented, more productive and R&D intensive. Furthermore, firms with patents are more intensely involved in this activity. Our results also suggest that the outsourcing of R&D in global markets by French firms is motivated by technology sourcing rather than cost‐saving interests.
Seroprevalence of Coxiella burnetii in Australian dogs
Authors: Shapiro A. J. , Norris J. M. , Heller J. , Brown G. , Malik R. , Bosward K. L. 
Published: January 2016

SummaryThe role of dogs in the transmission of Coxiella burnetii to humans is uncertain, and extensive seroprevalence studies of dogs have not been previously conducted in Australia. This study determined C. burnetii exposure in four diverse canine subpopulations by adapting, verifying and comparing an indirect immunofluoresence assay (IFA) and an enzyme‐linked immunosorbent assay (ELISA) used to detect anti‐C. burnetii antibodies in humans. Canine serum samples (n = 1223) were tested with IFA from four subpopulations [breeding establishments; household pets; free‐roaming dogs in Aboriginal communities; shelter dogs]. The proportions of seropositive dogs were as follows: breeding (7/309, 2.3%), household pets (10/328, 3%), Aboriginal communities (21/321, 6.5%) and shelters (5/265, 1.9%). Dogs from Aboriginal communities were 2.8 times (CI 1.5–5.1; P < 0.001) more likely to be seropositive than dogs from other populations. The ELISA was used on 86 of 1223 sera tested with IFA, and a Cohen's Kappa coefficient of 0.60 (CI 0.43–0.78) indicated good agreement between the two assays. This study has established that Australian dogs within all four subpopulations have been exposed to C. burnetii and that a higher seroprevalence was observed amongst free‐roaming dogs associated with Aboriginal communities. As C. burnetii recrudesces during pregnancy and birth products contain the highest concentration of organism, individuals assisting at the time of parturition, those handling pups shortly after birth as well as those residing in the vicinity of whelping dogs are potentially at risk of developing Q fever. However, the identification of active antigen shed in excreta from seropositive dogs is required in order to accurately define and quantify the public health risk.
Optimized
In Vitro
Antibiotic Susceptibility Testing Method for Small-Colony Variant Staphylococcus aureus
Authors: Precit Mimi R. , Wolter Daniel J. , Griffith Adam , Emerson Julia , Burns Jane L. , Hoffman Lucas R. 
Published: January 2016

ABSTRACT

Staphylococcus aureus
small-colony variants (SCVs) emerge frequently during chronic infections and are often associated with worse disease outcomes. There are no standardized methods for SCV antibiotic susceptibility testing (AST) due to poor growth and reversion to normal-colony (NC) phenotypes on standard media. We sought to identify reproducible methods for AST of
S. aureus
SCVs and to determine whether SCV susceptibilities can be predicted on the basis of treatment history, SCV biochemical type (auxotrophy), or the susceptibilities of isogenic NC coisolates. We tested the growth and stability of SCV isolates on 11 agar media, selecting for AST 2 media that yielded optimal SCV growth and the lowest rates of reversion to NC phenotypes. We then performed disk diffusion AST on 86
S. aureus
SCVs and 28 isogenic NCs and Etest for a subset of 26 SCVs and 24 isogenic NCs. Growth and reversion were optimal on brain heart infusion agar and Mueller-Hinton agar supplemented with compounds for which most clinical SCVs are auxotrophic: hemin, menadione, and thymidine. SCVs were typically nonsusceptible to either trimethoprim-sulfamethoxazole or aminoglycosides, in accordance with the auxotrophy type. In contrast, SCVs were variably nonsusceptible to fluoroquinolones, macrolides, lincosamides, fusidic acid, and rifampin;
mecA
-positive SCVs were invariably resistant to cefoxitin. All isolates (both SCVs and NCs) were susceptible to quinupristin-dalfopristin, vancomycin, minocycline, linezolid, chloramphenicol, and tigecycline. Analysis of SCV auxotrophy type, isogenic NC antibiograms, and antibiotic treatment history had limited utility in predicting SCV susceptibilities. With clinical correlation, this AST method and these results may prove useful in directing treatment for SCV infections.
Ultrafiltration and Microarray for Detection of Microbial Source Tracking Marker and Pathogen Genes in Riverine and Marine Systems
Authors: Li Xiang , Harwood Valerie J. , Nayak Bina , Weidhaas Jennifer L. 
Published: January 2016

ABSTRACT

Pathogen identification and microbial source tracking (MST) to identify sources of fecal pollution improve evaluation of water quality. They contribute to improved assessment of human health risks and remediation of pollution sources. An MST microarray was used to simultaneously detect genes for multiple pathogens and indicators of fecal pollution in freshwater, marine water, sewage-contaminated freshwater and marine water, and treated wastewater. Dead-end ultrafiltration (DEUF) was used to concentrate organisms from water samples, yielding a recovery efficiency of >95% for
Escherichia coli
and human polyomavirus. Whole-genome amplification (WGA) increased gene copies from ultrafiltered samples and increased the sensitivity of the microarray. Viruses (adenovirus, bocavirus, hepatitis A virus, and human polyomaviruses) were detected in sewage-contaminated samples. Pathogens such as
Legionella pneumophila
,
Shigella flexneri
, and
Campylobacter fetus
were detected along with genes conferring resistance to aminoglycosides, beta-lactams, and tetracycline. Nonmetric dimensional analysis of MST marker genes grouped sewage-spiked freshwater and marine samples with sewage and apart from other fecal sources. The sensitivity (percent true positives) of the microarray probes for gene targets anticipated in sewage was 51 to 57% and was lower than the specificity (percent true negatives; 79 to 81%). A linear relationship between gene copies determined by quantitative PCR and microarray fluorescence was found, indicating the semiquantitative nature of the MST microarray. These results indicate that ultrafiltration coupled with WGA provides sufficient nucleic acids for detection of viruses, bacteria, protozoa, and antibiotic resistance genes by the microarray in applications ranging from beach monitoring to risk assessment.
Enantioselective Synthesis of Vicinal (
R
,
R
)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase
Authors: Calam Eduard , González-Roca Eva , Fernández M. Rosario , Dequin Sylvie , Parés Xavier , Virgili Albert , Biosca Josep A. 
Published: January 2016

ABSTRACT

Butanediol dehydrogenase (Bdh1p) from
Saccharomyces cerevisiae
belongs to the superfamily of the medium-chain dehydrogenases and reductases and converts reversibly
R
-acetoin and
S
-acetoin to (2
R
,3
R
)-2,3-butanediol and
meso
-2,3-butanediol, respectively. It is specific for NAD(H) as a coenzyme, and it is the main enzyme involved in the last metabolic step leading to (2
R
,3
R
)-2,3-butanediol in yeast. In this study, we have used the activity of Bdh1p in different forms—purified enzyme, yeast extracts, permeabilized yeast cells, and as a fusion protein (with yeast formate dehydrogenase, Fdh1p)—to transform several vicinal diketones to the corresponding diols. We have also developed a new variant of the
delitto perfetto
methodology to place
BDH1
under the control of the
GAL1
promoter, resulting in a yeast strain that overexpresses butanediol dehydrogenase and formate dehydrogenase activities in the presence of galactose and regenerates NADH in the presence of formate. While the use of purified Bdh1p allows the synthesis of enantiopure (2
R
,3
R
)-2,3-butanediol, (2
R
,3
R
)-2,3-pentanediol, (2
R
,3
R
)-2,3-hexanediol, and (3
R
,4
R
)-3,4-hexanediol, the use of the engineered strain (as an extract or as permeabilized cells) yields mixtures of the diols. The production of pure diol stereoisomers has also been achieved by means of a chimeric fusion protein combining Fdh1p and Bdh1p. Finally, we have determined the selectivity of Bdh1p toward the oxidation/reduction of the hydroxyl/ketone groups from (2
R
,3
R
)-2,3-pentanediol/2,3-pentanedione and (2
R
,3
R
)-2,3-hexanediol/2,3-hexanedione. In conclusion, Bdh1p is an enzyme with biotechnological interest that can be used to synthesize chiral building blocks. A scheme of the favored pathway with the corresponding intermediates is proposed for the Bdh1p reaction.
Genomic Comparison of Two O111:H
−
Enterohemorrhagic Escherichia coli Isolates from a Historic Hemolytic-Uremic Syndrome Outbreak in Australia
Authors: McAllister Lauren J. , Bent Stephen J. , Petty Nicola K. , Skippington Elizabeth , Beatson Scott A. , Paton James C. , Paton Adrienne W. 
Published: January 2016

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) is an important cause of diarrhea and hemolytic-uremic syndrome (HUS) worldwide. Australia's worst outbreak of HUS occurred in Adelaide in 1995 and was one of the first major HUS outbreaks attributed to a non-O157 Shiga-toxigenic
E. coli
(STEC) strain. Molecular analyses conducted at the time suggested that the outbreak was caused by an O111:H
−
clone, with strains from later in the outbreak harboring an extra copy of the genes encoding the potent Shiga toxin 2 (Stx2). Two decades later, we have used next-generation sequencing to compare two isolates from early and late in this important outbreak. We analyzed genetic content, single-nucleotide polymorphisms (SNPs), and prophage insertion sites; for the latter, we demonstrate how paired-end sequence data can be leveraged to identify such insertion sites. The two strains are genetically identical except for six SNP differences and the presence of not one but two additional Stx2-converting prophages in the later isolate. Isolates from later in the outbreak were associated with higher levels of morbidity, suggesting that the presence of the additional Stx2-converting prophages is significant in terms of the virulence of this clone.
Therapeutic Role of Interleukin 22 in Experimental Intra-abdominal Klebsiella pneumoniae Infection in Mice
Authors: Zheng Mingquan , Horne William , McAleer Jeremy P. , Pociask Derek , Eddens Taylor , Good Misty , Gao Bin , Kolls Jay K. 
Published: January 2016

ABSTRACT

Interleukin 22 (IL-22) is an IL-10-related cytokine produced by T helper 17 (Th17) cells and other immune cells that signals via IL-22 receptor alpha 1 (IL-22Ra1), which is expressed on epithelial tissues, as well as hepatocytes. IL-22 has been shown to have hepatoprotective effects that are mediated by signal transducer and activator of transcription 3 (STAT3) signaling. However, it is unclear whether IL-22 can directly regulate antimicrobial programs in the liver. To test this hypothesis, hepatocyte-specific IL-22Ra1 knockout (
Il22Ra1
Hep−/−
) and Stat3 knockout (
Stat3

Hep
−/−

) mice were generated and subjected to intra-abdominal infection with
Klebsiella pneumoniae
, which results in liver injury and necrosis. We found that overexpression of IL-22 or therapeutic administration of recombinant IL-22 (rIL-22), given 2 h postinfection, significantly reduced the bacterial burden in both the liver and spleen. The antimicrobial activity of rIL-22 required hepatic
Il22Ra1
and
Stat3
. Serum from rIL-22-treated mice showed potent bacteriostatic activity against
K. pneumoniae
, which was dependent on lipocalin 2 (LCN2). However,
in vivo
, rIL-22-induced antimicrobial activity was only partially reduced in LCN2-deficient mice. We found that rIL-22 also induced serum amyloid A2 (SAA2) and that SAA2 had anti-
K. pneumoniae
bactericidal activity
in vitro
. These results demonstrate that IL-22, through IL-22Ra1 and STAT3 singling, can induce intrinsic antimicrobial activity in the liver, which is due in part to LCN2 and SAA2. Therefore, IL-22 may be a useful adjunct in treating hepatic and intra-abdominal infections.
Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci
Authors: Pollet Rebecca M. , Ingle James D. , Hymes Jeff P. , Eakes Thomas C. , Eto Karina Yui , Kwong Stephen M. , Ramsay Joshua P. , Firth Neville , Redinbo Matthew R. 
Published: January 2016

ABSTRACT

Antimicrobial resistance in
Staphylococcus aureus
presents an increasing threat to human health. This resistance is often encoded on mobile plasmids, such as pSK41; however, the mechanism of transfer of these plasmids is not well understood. In this study, we first examine key protein-DNA interactions formed by the relaxase enzyme, NES, which initiates and terminates the transfer of the multidrug resistance plasmid pSK41. Two loops on the NES protein, hairpin loops 1 and 2, form extensive contacts with the DNA hairpin formed at the
oriT
region of pSK41, and here we establish that these contacts are essential for proper DNA cleavage and religation by the full 665-residue NES protein
in vitro
. Second, pSK156 and pCA347 are nonconjugative
Staphylococcus aureus
plasmids that contain sequences similar to the
oriT
region of pSK41 but differ in the sequence predicted to form a DNA hairpin. We show that pSK41-encoded NES is able to bind, cleave, and religate the
oriT
sequences of these nonconjugative plasmids
in vitro
. Although pSK41 could mobilize a coresident plasmid harboring its cognate
oriT
, it was unable to mobilize plasmids containing the pSK156 and pCA347 variant
oriT
mimics, suggesting that an accessory protein like that previously shown to confer specificity in the pWBG749 system may also be involved in transmission of plasmids containing a pSK41-like
oriT
. These data indicate that the conjugative relaxase in
trans
mechanism recently described for the pWBG749 family of plasmids also applies to the pSK41 family of plasmids, further heightening the potential significance of this mechanism in the horizontal transfer of staphylococcal plasmids.

IMPORTANCE
Understanding the mechanism of antimicrobial resistance transfer in bacteria such as
Staphylococcus aureus
is an important step toward potentially slowing the spread of antimicrobial-resistant infections. This work establishes protein-DNA interactions essential for the transfer of the
Staphylococcus aureus
multiresistance plasmid pSK41 by its relaxase, NES. This enzyme also processed variant
oriT
-like sequences found on numerous plasmids previously considered nontransmissible, suggesting that in conjunction with an uncharacterized accessory protein, these plasmids may be transferred horizontally via a relaxase in
trans
mechanism. These findings have important implications for our understanding of staphylococcal resistance plasmid evolution.
Electrocardiographic abnormalities in elite high school athletes: comparison to adolescent hypertrophic cardiomyopathy
Authors: Thompson Alex J , Cannon Bryan C , Wackel Philip L , Horner Justin M , Ackerman Michael J , O'Leary Patrick W , Eidem Benjamin W , Johnson Jonathan N 
Published: January 2016

BackgroundIn athletes, ECG changes from physiological cardiac remodelling are common but can overlap with findings from a pathological disorder. We compared ECG findings in a group of elite high school athletes to a cohort of adolescents with hypertrophic cardiomyopathy (HCM).Methods/resultsWe prospectively performed 15-lead ECGs and echocardiograms in 147 elite high school athletes. Student-athlete ECGs were compared in blinded fashion to ECGs of 148 adolescents with HCM of similar age and ethnicity. Standard ECG hypertrophy criteria and established expert opinion guidelines (European Society of Cardiology, ESC and Seattle criteria) were analysed. All student-athletes had normal echocardiograms. Overall, 77/147 (52%) of student-athletes met standard ECG criteria for ventricular hypertrophy compared to 126/148 (85%) adolescents with HCM (p<0.0001). There were 112/148 (76%) adolescents with HCM who had pathological Q-waves, T-wave inversion and/or ST-segment depression compared to 1/147 (1%) athletes (p<0.0001). Most patients with HCM (84%, 124/148) had ≥1 abnormal ECG finding(s) according to Seattle criteria, compared to 1% of student-athletes (2/147). Similarly, 130/148 (88%) patients with HCM met group-2 ESC criteria (abnormal), compared to 36/147 (24%) student-athletes (p<0.0001).ConclusionsOver 50% of elite high school athletes with echocardiographically confirmed normal hearts satisfied standard voltage criteria for ventricular hypertrophy. Pathological Q-waves, T-wave inversion or ST-segment depression were most helpful in distinguishing adolescents with HCM from normals. Both ESC and Seattle criteria successfully stratified the student-athlete and HCM cohorts, however each had a false-negative rate >10% for the HCM cohort. The Seattle criteria demonstrated a significantly lower false-positive rate (1%) than the ESC criteria (24%).
Understanding pathways to breast cancer diagnosis among women in the Western Cape Province, South Africa: a qualitative study
Authors: Moodley Jennifer , Cairncross Lydia , Naiker Thurandrie , Momberg Mariette 
Published: January 2016

ObjectivesThe aim of this study was to explore and understand women's pathways to breast cancer diagnosis and factors influencing this journey.Design and settingIndepth interviews were conducted with clients at a tertiary level breast cancer clinic in Cape Town, South Africa. A thematic analysis was performed underpinned by the theoretical concepts of the Model of Pathways to Treatment framework.Participants20 women were interviewed within 1 week of being diagnosed with breast cancer.ResultsThe average time between discovery of bodily changes to breast cancer diagnosis was 8.5 months. Deficits in breast self-awareness and knowledge of breast cancer symptoms delayed women's interpretation of bodily changes as being abnormal. All women first noticed breast lumps; however, many did not perceive it as abnormal until additional symptoms were present. General good health, attribution of symptoms to ageing, and past benign breast disease resulted in women being complacent about bodily changes. Disclosure to family members served as a trigger to seek healthcare. The initial type of primary level care services women accessed was influenced by perceptions of care each service provided, finances, structural factors, and personal safety related to the physical location of services.ConclusionsSymptom appraisal and interpretation contributed significantly to delayed presentation. To improve timely diagnosis of breast cancer, interventions that increase women's confidence in detecting breast changes, improve knowledge of breast cancer symptoms, address myths, and encourage prompt help-seeking behaviour are required.