bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of complement factor B allotypes and serum biomarkers in rheumatoid arthritis patients and their relatives
Authors: Nass F. R. , Skare T. L. , Goeldner I. , Nisihara R. , Messias‐Reason I. J. , Utiyama S. R. R.
Published: September 2015

The aim of the study was to investigate the allotypic variability of complement factor B (BF) in patients and relatives with rheumatoid arthritis (RA) and its association with serological biomarkers and clinical features of the disease. BF allotypes were determined by high‐voltage agarose gel electrophoresis in serum samples of 180 patients with RA, 198 relatives and 98 controls from Southern Brazil. Anticyclic citrullinated peptide (anti‐CCP), antimutated citrullinated vimentin (anti‐MCV) and IgA‐rheumatoid factor (RF) were determined by ELISA and IgM‐RF by latex agglutination in all samples. No significant differences were found in the allotypic variants of BF between patients with RA, relatives and controls, nor associations with gender and age of RA onset. BF*S07 allotype was significantly associated with extra‐articular manifestations (EAMs; Secondary Sjögren Syndrome, pneumonitis, rheumatoid nodules) in patients with RA (P = 0.02; OR = 6.62). Patients with phenotype BF F had lower positivity for anti‐MCV biomarker (P = 0.02; OR = 0.22) and those with allotype BF*S had higher prevalence of this autoantibody (P = 0.02; OR = 3.77). An increased frequency of RF‐IgA was detected in relatives of patients with RA with BF FS07 phenotype (P = 0.02; OR = 7.78). Complement BF variability did not influence the development of RA in the studied patients, but BF variants may act as markers of disease prognosis, such as development of EAMs, corroborating with the role of the alternative pathway in the pathogenesis of RA.
HLA‐A locus allelic dropout in Sanger sequence‐based typing due to the single nucleotide polymorphism of exon 1
Authors: Zhang W. , He Y. , Wang W. , Han Z. , He J. , Chen N. , Dong L. , Tao S. , He J. , Zhu F. , Lv H.
Published: September 2015

The DNA‐based method is used widely for HLA genotyping in routine work, but some allele may be dropout in the genotyping procedure. Here, we reported a case with HLA‐A allele dropout in the Sanger PCR‐SBT test. The initial PCR‐SBT method with a commercial agent kit was not characterized, and the result of Luminex technology indicated the dropout as a HLA‐A*02 allele. Subsequently, the sequences of exons 2–4 were fully matched with the A*02:07 and A*11:01:01 by allele group‐specific primer amplification PCR‐SBT. On further analysis, a novel allele A*02:07:07 was identified, which has one nucleotide difference from A*02:07:01 at position 6 C>G of exon 1. According to the sequencing for 5′‐UTR to 3′‐UTR, the novel single nucleotide polymorphism of exon 1 was contributed to HLA‐A locus allele dropout in the sample. Our results indicated multiplatform analysis is necessary when a conclusive HLA type cannot be determined by a single methodology.
Annual Research Review: Threats to the validity of child psychiatry and psychology
Authors: Rutter Michael , Pickles Andrew
Published: September 2015

Background

Suggestions have been made that many claims concern false‐positive findings in the field of child psychology and psychiatry.

Findings

The literature was searched for concepts and findings on the validity of child psychiatry and psychology. Substantial progress has been made in some, but not all, areas and considerable challenges remain in all.

Conclusions

The two major threats to validity concern the inability to examine brain tissues in life and the evidence that there is a high overlap among disorders. We emphasize the need to follow published guidelines on preplanned analyses and we note the dangers associated with unregulated flexibility in data analysis. We note the very important clinical and developmental findings that have been ignored, perhaps partly because of an excessive focus on technologies. Nevertheless, we are positive about both the accomplishments and the ways in which challenges are being met.
Vermistella arctica n. sp. Nominates the Genus Vermistella as a Candidate for Taxon with Bipolar Distribution
Authors: Tyml Tomáš , Kostka Martin , Ditrich Oleg , Dyková Iva
Published: September 2015

A new amoebozoan species, Vermistella arctica n. sp., is described from marine habitats in the central part of Svalbard archipelago. This is the first report on Arctic amoebae belonging to the genus Vermistella Moran and Anderson, 2007, the type species of which was described from the opposite pole of the planet. Psychrophily proved in the new strains qualifies the genus Vermistella as a bipolar taxon. Molecular phylogenetic analyses based on 18S rDNA and actin sequences did not show any affinity of the genus Vermistella to Stygamoeba regulata ATCC® 50892™ strain. A close phylogenetic relationship was found between Vermistella spp. and a sequence originating from an environmental sample from Cariaco basin, the largest marine permanently anoxic system in the world. Possible mechanisms of bipolar distribution are discussed.
Excellent post‐transplant survival in patients with intermediate stage hepatocellular carcinoma responding to neoadjuvant therapy
Authors: Finkenstedt Armin , Vikoler Anja , Portenkirchner Manuela , Mülleder Kerstin , Maglione Manuel , Margreiter Christian , Moser Patrizia , Vogel Wolfgang , Bale Reto , Freund Martin , Luger Anna , Tilg Herbert , Petersen Johannes , Schneeberger Stefan , Graziadei Ivo , Zoller Heinz , Glodny Bernhard
Published: September 2015

Background & Aims

Current treatment guidelines preclude liver transplantation for patients with BCLC B (intermediate stage) HCC, and expanding transplantation criteria for selected patients beyond early stage HCC remains controversial. The aim of this study was to determine stage‐dependent HCC recurrence and overall survival rates in transplant recipients and the impact of response to neoadjuvant treatment on outcome.

Methods

The CT/MRI scans of patients who underwent liver transplantation for HCC at our transplant centre during a time period of 12 years were reviewed by two radiologists to assess tumour stage and response to neoadjuvant treatment according to mRECIST.

Results

Of 174 HCC patients, 48 (28%) were BCLC intermediate stage. Neoadjuvant treatment was performed in 94% of patients. When patients were stratified according to tumour stage, no significant difference in overall survival was observed between very early or early and intermediate stage. When stratified according to treatment response, patients with complete response had a 5‐year overall survival of 87%, which was significantly higher than in patients with progressive disease (62%, P = 0.02). HCC recurrence in intermediate stage patients without disease progression after neoadjuvant treatment was equal to that in patients with very early or early stage HCC. Tumour grading, histological and radiological evidence of vascular invasion, but not tumour stage were identified as independent risk factors for HCC recurrence.

Conclusions

Liver transplantation may be an option for selected patients with BCLC intermediate stage HCC and complete response after neoadjuvant treatment because of excellent long‐term survival and low recurrence rates.
Heterogeneity of non‐alcoholic fatty liver disease
Authors: Yki‐Järvinen Hannele , Luukkonen Panu K.
Published: September 2015

See Article on Page 2537
Transcriptional variation associated with cactus host plant adaptation in Drosophila mettleri populations
Authors: Hoang Kim , Matzkin Luciano M. , Bono Jeremy M.
Published: September 2015

Although the importance of host plant chemistry in plant–insect interactions is widely accepted, the genetic basis of adaptation to host plants is not well understood. Here, we investigate transcriptional changes associated with a host plant shift in Drosophila mettleri. While D. mettleri is distributed mainly throughout the Sonoran Desert where it specializes on columnar cacti (Carnegiea gigantea and Pachycereus pringleii), a population on Santa Catalina Island has shifted to chemically divergent coastal prickly pear cactus (Opuntia littoralis). We compared gene expression of larvae from the Sonoran Desert and Santa Catalina Island when reared on saguaro (C. gigantea), coastal prickly pear and laboratory food. Consistent with expectations based on the complexity and toxicity of cactus relative to laboratory food, within‐population comparisons between larvae reared on these food sources revealed transcriptional differences in detoxification and other metabolic pathways. The majority of transcriptional differences between populations on the cactus hosts were independent of the rearing environment and included a disproportionate number of genes involved in processes relevant to host plant adaptation (e.g. detoxification, central metabolism and chemosensory pathways). Comparisons of transcriptional reaction norms between the two populations revealed extensive shared plasticity that likely allowed colonization of coastal prickly pear on Santa Catalina Island. We also found that while plasticity may have facilitated subsequent adaptive divergence in gene expression between populations, the majority of genes that differed in expression on the novel host were not transcriptionally plastic in the presumed ancestral state.
Evaluation of the effects of Streptococcus mutans chaperones and protein secretion machinery components on cell surface protein biogenesis, competence, and mutacin production
Authors: Crowley P.J. , Brady L.J.
Published: September 2015

The respective contributions of components of the protein translocation/maturation machinery to cell surface biogenesis in Streptococcus mutans are not fully understood. Here we used a genetic approach to characterize the effects of deletion of genes encoding the ribosome‐associated chaperone RopA (Trigger Factor), the surface‐localized foldase PrsA, and the membrane‐localized chaperone insertases YidC1 and YidC2, both singly and in combination, on bacterial growth, chain length, self‐aggregation, cell surface hydrophobicity, autolysis, and antigenicity of surface proteins P1 (AgI/II, PAc), WapA, GbpC, and GtfD. The single and double deletion mutants, as well as additional mutant strains lacking components of the signal recognition particle pathway, were also evaluated for their effects on mutacin production and genetic competence.
Diurnal patterns in Scots pine stem oleoresin pressure in a boreal forest
Authors: Rissanen K. , Hölttä T. , Vanhatalo A. , Aalto J. , Nikinmaa E. , Rita H. , Bäck J.
Published: September 2015

Coniferous tree stems contain large amounts of oleoresin under positive pressure in the resin ducts. Studies in North‐American pines indicated that the stem oleoresin exudation pressure (OEP) correlates negatively with transpiration rate and soil water content. However, it is not known how the OEP changes affect the emissions of volatile vapours from the trees. We measured the OEP, xylem diameter changes indicating changes in xylem water potential and monoterpene emissions under field conditions in mature Scots pine (Pinus sylvestris L.) trees in southern Finland. Contrary to earlier reports, the diurnal OEP changes were positively correlated with temperature and transpiration rate. OEP was lowest at the top part of the stem, where water potentials were also more negative, and often closely linked to ambient temperature and stem monoterpene emissions. However, occasionally OEP was affected by sudden changes in vapour pressure deficit (VPD), indicating the importance of xylem water potential on OEP as well. We conclude that the oleoresin storage pools in tree stems are in a dynamic relationship with ambient temperature and xylem water potential, and that the canopy monoterpene emission rates may therefore be also regulated by whole tree processes and not only by the conditions prevailing in the upper canopy.
The Arabidopsis F‐box E3 ligase RIFP1 plays a negative role in abscisic acid signalling by facilitating ABA receptor RCAR3 degradation
Authors: Li Ying , Zhang Liang , Li Dekuan , Liu Zhibin , Wang Jianmei , Li Xufeng , Yang Yi
Published: September 2015

The phytohormone abscisic acid (ABA) plays a vital role in plant growth and development. The function of ABA is mediated by a group of newly discovered ABA receptors, named PYRABACTIN RESISTANCE 1/PYR‐LIKE/REGULATORY COMPONENTS OF ABA RECEPTORs (PYR1/PYLs/RCARs). Here, we report that an Arabidopsis thaliana F‐box protein RCAR3 INTERACTING F‐BOX PROTEIN 1 (RIFP1) interacts with ABA receptor (RCAR3) and SCF E3 ligase complex subunits Arabidopsis SKP1‐LIKE PROTEINs (ASKs) in vitro and in vivo. The rifp1 mutant plants displayed increased ABA‐mediated inhibition of seed germination and water loss of detached leaves, while the overexpression of RIFP1 in Arabidopsis led to plants being insensitive to ABA. Meanwhile, the rifp1 mutant plants showed greater tolerance to water deficit. In addition, the RCAR3 protein level was more stable in the rifp1 mutant plants than in the wild‐type plants, indicating that RIFP1 facilitates the proteasome degradation of RCAR3. Accordingly, the loss of RIFP1 increased the transcript levels of several ABA‐responsive genes. Taken together, these data indicate that RIFP1 plays a negative role in the RCAR3‐mediated ABA signalling pathway and likely functions as an adaptor subunit of the SCF ubiquitin ligase complex to regulate ABA receptor RCAR3 stability.
Temporal kinetics of the transcriptional response to carbon depletion and sucrose readdition in Arabidopsis seedlings
Authors: Cookson Sarah Jane , Yadav Umesh Prasad , Klie Sebastian , Morcuende Rosa , Usadel Björn , Lunn John Edward , Stitt Mark
Published: September 2015

To investigate whether the transcriptional response to carbon (C) depletion and sucrose resupply depends on the duration and severity of the C depletion, Arabidopsis seedlings were grown in liquid culture and harvested 3, 6, 12, 24, 48 and 72 h after removing sucrose from the medium and 30 min after resupplying sucrose at each time. Expression profiling revealed early transcriptional inhibition of cell wall synthesis and remodelling of signalling, followed by induction of C recycling and photosynthesis and general inhibition of growth. The temporal sequence differed from the published response to progressive exhaustion of C during a night and extended night in vegetatively growing plants. The response to sucrose readdition was conserved across the C‐depletion time course. Intriguingly, the vast majority of rapidly responding transcripts decreased rather than increased. The majority of transcripts that respond rapidly to sucrose and many transcripts that respond during C depletion also decrease after treating seedlings with the transcriptional inhibitor cordycepin A. Comparison with published responses to overexpression of otsA, AKIN10 and bZIP11 revealed that many genes that respond to C depletion, and especially sucrose resupply, respond to one or more of these C‐signalling components. Thus, multiple factors contribute to C responsiveness, including many signalling components, transcriptional regulation and transcript turnover.
Collaboration between competitors' NPD teams: in search of effective modes of management control
Authors: Smets Lydie P.M. , Langerak Fred , Tatikonda Mohan V.
Published: September 2015

Successful collaboration between new product development (NPD) teams maintained by competitors (so‐called horizontal NPD collaboration) requires the use of formal modes of management control that simultaneously coordinate the teams' interdependent development activities and encourage their cooperative behavior. Nevertheless, prior theoretical and empirical research suggests that formal control modes required to improve coordination may also drive uncooperative, opportunistic behavior. To help managers in horizontal NPD collaborations select appropriate control modes, this study draws on organizational theory of management control and develops a conceptual framework that specifies the impact of one partner's use of input, process, and output controls on the other partner's perception of coordination effectiveness and cooperative behavior. The results of a scenario‐based experiment with 110 expert practitioners show that managers perceive the competitor's use of input control as harmful and process control as helpful for achieving coordination effectiveness. Moreover, managers respond positively to the competitor's use of input control and negatively to the competitor's use of output control when it comes to cooperative behavior. Together, the results indicate that no single mode of formal management control simultaneously enhances both coordination and cooperative behavior in horizontal NPD collaborations.
Twitter and Political Campaigning
Authors: Vergeer Maurice
Published: September 2015

The use of Twitter by politicians, parties, and the general audience in politics, particularly during election campaigns, has become an extremely popular research field almost overnight. Even though Twitter, a medium that emerged early in 2006 – the first tweet was posted on 21 March 2006 by Jack Dorsey, co‐founder of Twitter – and elections occurring only every few years, it has already received much academic attention. The studies produced are very diverse, ranging from analyzing how politicians or citizens use Twitter, to looking at their activities and the content of political Twitter messages, to network studies of Twitter users. This review will cover many types of studies that characterize the field. The large diversity in the studies conducted on elections will be represented in this review of approaches.
Over the Hill, Under Siege: Labor Force Graying, Labor Market Pushes, and Consequences for Life Chances
Authors: Lassus Lora A. Phillips
Published: September 2015

Interest in older workers has recently expanded due to concerns over labor force “graying.” Research and policy on aging adults' labor market participation have, thus far, framed the decision to labor as one shaped solely by the desires and capacities of older workers themselves. This perspective fails to recognize how multiple employer‐side barriers play a large role in defining – and limiting – available choices. In this review, I synthesize the multi‐disciplinary literature on employer‐side barriers to older workers' labor market participation. In particular, I identify and discuss individual‐, meso‐, and social structural‐level barriers that uniquely affect this group, noting where gaps in understanding remain. I consider older workers primarily as a whole to demonstrate how age operates as a distinct, important identity; however, I also reflect on how age overlaps with both other identities and cohort membership. Next, I briefly consider the relationship between these employer‐side barriers and aging adults' life chances, particularly in an era of austerity. Although I focus on the United States case, I also note key cross‐national similarities and differences. Finally, reflecting upon the foregoing review, I suggest that a redirection of public policy is necessary to effectively respond to this contemporary demographic shift.
Beyond the Sociology of Diagnosis
Authors: Jutel Annemarie
Published: September 2015

The sociology of diagnosis offers a vantage point from which to study health and illness, linking a number of other threads of sociological thought. While there has been a growing interest in diagnosis since Mildred Blaxter's suggestion for a sociological exploration in 1978 – a call echoed by Brown in 1990 – it is timely to reflect upon the way in which sociologists engage with diagnosis. Within this review essay, I first consider what it is to “be a sociology” in general terms. I then explore the implications of this for an effective sociology of diagnosis, discussing the priorities it has recently developed as well as the directions its scholars might consider. Finally, I suggest ways in which sociologists of diagnosis could broaden their approach in order to advance their understanding of health, illness, and medicine.
Computing interaural differences through finite element modeling of idealized human heads
Authors: Cai Tingli , Rakerd Brad , Hartmann William M.
Published: September 2015

Acoustical interaural differences were computed for a succession of idealized shapes approximating the human head-related anatomy: sphere, ellipsoid, and ellipsoid with neck and torso. Calculations were done as a function of frequency (100–2500 Hz) and for source azimuths from 10 to 90 degrees using finite element models. The computations were compared to free-field measurements made with a manikin. Compared to a spherical head, the ellipsoid produced greater large-scale variation with frequency in both interaural time differences and interaural level differences, resulting in better agreement with the measurements. Adding a torso, represented either as a large plate or as a rectangular box below the neck, further improved the agreement by adding smaller-scale frequency variation. The comparisons permitted conjectures about the relationship between details of interaural differences and gross features of the human anatomy, such as the height of the head, and length of the neck.
Multinational teams and diseconomies of scale in collaborative research
Authors: Hsiehchen David , Espinoza Magdalena , Hsieh Antony
Published: September 2015

Larger research teams are linked to decreasing impact, whereas contributions by international coauthors result in citation gains.
Transcriptional regulation of APOBEC3 antiviral immunity through the CBF-β/RUNX axis
Authors: Anderson Brett D. , Harris Reuben S.
Published: September 2015

HIV hijacks a single host protein to thwart a powerful antiviral defense on two fronts.
Unraveling the storage mechanism in organic carbonyl electrodes for sodium-ion batteries
Authors: Wu Xiaoyan , Jin Shifeng , Zhang Zhizhen , Jiang Liwei , Mu Linqin , Hu Yong-Sheng , Li Hong , Chen Xiaolong , Armand Michel , Chen Liquan , Huang Xuejie
Published: September 2015

Na-O layer provides Na
+
diffusion pathway and storage site, whereas benzene layer provides e−conduction pathway and redox center.
Metabolic Pathway Involved in 2-Methyl-6-Ethylaniline Degradation by Sphingobium sp. Strain MEA3-1 and Cloning of the Novel Flavin-Dependent Monooxygenase System
meaBA
Authors: Dong Weiliang , Chen Qiongzhen , Hou Ying , Li Shuhuan , Zhuang Kai , Huang Fei , Zhou Jie , Li Zhoukun , Wang Jue , Fu Lei , Zhang Zhengguang , Huang Yan , Wang Fei , Cui Zhongli
Published: September 2015

2-Methyl-6-ethylaniline (MEA) is the main microbial degradation intermediate of the chloroacetanilide herbicides acetochlor and metolachlor.
Sphingobium
sp. strain MEA3-1 can utilize MEA and various alkyl-substituted aniline and phenol compounds as sole carbon and energy sources for growth. We isolated the mutant strain MEA3-1Mut, which converts MEA only to 2-methyl-6-ethyl-hydroquinone (MEHQ) and 2-methyl-6-ethyl-benzoquinone (MEBQ). MEA may be oxidized by the P450 monooxygenase system to 4-hydroxy-2-methyl-6-ethylaniline (4-OH-MEA), which can be hydrolytically spontaneously deaminated to MEBQ or MEHQ. The MEA microbial metabolic pathway was reconstituted based on the substrate spectra and identification of the intermediate metabolites in both the wild-type and mutant strains. Plasmidome sequencing indicated that both strains harbored 7 plasmids with sizes ranging from 6,108 bp to 287,745 bp. Among the 7 plasmids, 6 were identical, and pMEA02′ in strain MEA3-1Mut lost a 37,000-bp fragment compared to pMEA02 in strain MEA3-1. Two-dimensional electrophoresis (2-DE) and protein mass fingerprinting (PMF) showed that MEA3-1Mut lost the two-component flavin-dependent monooxygenase (TC-FDM) MeaBA, which was encoded by a gene in the lost fragment of pMEA02. MeaA shared 22% to 25% amino acid sequence identity with oxygenase components of some TC-FDMs, whereas MeaB showed no sequence identity with the reductase components of those TC-FDMs. Complementation with
meaBA
in MEA3-1Mut and heterologous expression in
Pseudomonas putida
strain KT2440 resulted in the production of an active MEHQ monooxygenase.
Transcriptomic Analysis of Shiga-Toxigenic Bacteriophage Carriage Reveals a Profound Regulatory Effect on Acid Resistance in Escherichia coli
Authors: Veses-Garcia Marta , Liu Xuan , Rigden Daniel J. , Kenny John G. , McCarthy Alan J. , Allison Heather E.
Published: September 2015

Shiga-toxigenic bacteriophages are converting lambdoid phages that impart the ability to produce Shiga toxin to their hosts. Little is known about the function of most of the genes carried by these phages or the impact that lysogeny has on the
Escherichia coli
host. Here we use next-generation sequencing to compare the transcriptomes of
E. coli
strains infected with an Stx phage, before and after triggering of the bacterial SOS response that initiates the lytic cycle of the phage. We were able to discriminate between bacteriophage genes expressed in the lysogenic and lytic cycles, and we describe transcriptional changes that occur in the bacterial host as a consequence of Stx phage carriage. Having identified upregulation of the glutamic acid decarboxylase (GAD) operon, confirmed by reverse transcription-quantitative PCR (RT-qPCR), we used phenotypic assays to establish the ability of the Stx prophage to confer a greater acid resistance phenotype on the
E. coli
host. Known phage regulators were overexpressed in
E. coli
, and the acid resistance of the recombinant strains was tested. The phage-encoded transcriptional regulator CII was identified as the controller of the acid response in the lysogen. Infection of an
E. coli
O157 strain, from which integrated Stx prophages were previously removed, showed increased acid resistance following infection with a nontoxigenic phage, ϕ24
B
. In addition to demonstrating this link between Stx phage carriage and
E. coli
acid resistance, with its implications for survival postingestion, the data set provides a number of other potential insights into the impact of lambdoid phage carriage on the biology of
E. coli
.
Global Transcriptome and Mutagenic Analyses of the Acid Tolerance Response of Salmonella enterica Serovar Typhimurium
Authors: Ryan Daniel , Pati Niladri Bhusan , Ojha Urmesh K. , Padhi Chandrashekhar , Ray Shilpa , Jaiswal Sangeeta , Singh Gajinder P. , Mannala Gopala K. , Schultze Tilman , Chakraborty Trinad , Suar Mrutyunjay
Published: September 2015

Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) is one of the leading causative agents of food-borne bacterial gastroenteritis. Swift invasion through the intestinal tract and successful establishment in systemic organs are associated with the adaptability of
S
. Typhimurium to different stress environments. Low-pH stress serves as one of the first lines of defense in mammalian hosts, which
S
. Typhimurium must efficiently overcome to establish an infection. Therefore, a better understanding of the molecular mechanisms underlying the adaptability of
S
. Typhimurium to acid stress is highly relevant. In this study, we have performed a transcriptome analysis of
S
. Typhimurium under the acid tolerance response (ATR) and found a large number of genes (∼47%) to be differentially expressed (more than 1.5-fold or less than −1.5-fold;
P
< 0.01). Functional annotation revealed differentially expressed genes to be associated with regulation, metabolism, transport and binding, pathogenesis, and motility. Additionally, our knockout analysis of a subset of differentially regulated genes facilitated the identification of proteins that contribute to
S
. Typhimurium ATR and virulence. Mutants lacking genes encoding the K
+
binding and transport protein KdpA, hypothetical protein YciG, the flagellar hook cap protein FlgD, and the nitrate reductase subunit NarZ were significantly deficient in their ATRs and displayed varied
in vitro
virulence characteristics. This study offers greater insight into the transcriptome changes of
S
. Typhimurium under the ATR and provides a framework for further research on the subject.
Helicobacter pullorum Isolated from Fresh Chicken Meat: Antibiotic Resistance and Genomic Traits of an Emerging Foodborne Pathogen
Authors: Borges Vítor , Santos Andrea , Correia Cristina Belo , Saraiva Margarida , Ménard Armelle , Vieira Luís , Sampaio Daniel A. , Pinheiro Miguel , Gomes João Paulo , Oleastro Mónica
Published: September 2015

Meat and meat products are important sources of human intestinal infections. We report the isolation of
Helicobacter pullorum
strains from chicken meat. Bacteria were isolated from 4 of the 17 analyzed fresh chicken meat samples, using a membrane filter method. MIC determination revealed that the four strains showed acquired resistance to ciprofloxacin; one was also resistant to erythromycin, and another one was resistant to tetracycline. Whole-genome sequencing of the four strains and comparative genomics revealed important genetic traits within the
H. pullorum
species, such as 18 highly polymorphic genes (including a putative new cytotoxin gene), plasmids, prophages, and a complete type VI secretion system (T6SS). The T6SS was found in three out of the four isolates, suggesting that it may play a role in
H. pullorum
pathogenicity and diversity. This study suggests that the emerging pathogen
H. pullorum
can be transmitted to humans by chicken meat consumption/contact and constitutes an important contribution toward a better knowledge of the genetic diversity within the
H. pullorum
species. In addition, some genetic traits found in the four strains provide relevant clues to how this species may promote adaptation and virulence.
Poultry Body Temperature Contributes to Invasion Control through Reduced Expression of Salmonella Pathogenicity Island 1 Genes in Salmonella enterica Serovars Typhimurium and Enteritidis
Authors: Troxell Bryan , Petri Nicholas , Daron Caitlyn , Pereira Rafaela , Mendoza Mary , Hassan Hosni M. , Koci Matthew D.
Published: September 2015

Salmonella enterica
serovars Typhimurium (
S
. Typhimurium) and Enteritidis (
S
. Enteritidis) are foodborne pathogens, and outbreaks are often associated with poultry products. Chickens are typically asymptomatic when colonized by these serovars; however, the factors contributing to this observation are uncharacterized. Whereas symptomatic mammals have a body temperature between 37°C and 39°C, chickens have a body temperature of 41°C to 42°C. Here,
in vivo
experiments using chicks demonstrated that numbers of viable
S
. Typhimurium or
S
. Enteritidis bacteria within the liver and spleen organ sites were ≥4 orders of magnitude lower than those within the ceca. When similar doses of
S
. Typhimurium or
S
. Enteritidis were given to C3H/HeN mice, the ratio of the intestinal concentration to the liver/spleen concentration was 1:1. In the avian host, this suggested poor survival within these tissues or a reduced capacity to traverse the host epithelial layer and reach liver/spleen sites or both.
Salmonella
pathogenicity island 1 (SPI-1) promotes localization to liver/spleen tissues through invasion of the epithelial cell layer. Following
in vitro
growth at 42°C, SPI-1 genes
sipC
,
invF
, and
hilA
and the SPI-1
rtsA
activator were downregulated compared to expression at 37°C. Overexpression of the
hilA
activators
fur
,
fliZ
, and
hilD
was capable of inducing
hilA-lacZ
at 37°C but not at 42°C despite the presence of similar levels of protein at the two temperatures. In contrast, overexpression of either
hilC
or
rtsA
was capable of inducing
hilA
and
sipC
at 42°C. These data indicate that physiological parameters of the poultry host, such as body temperature, have a role in modulating expression of virulence.
Electroacupuncture Alleviates Cisplatin-Induced Nausea in Rats
Authors: Cui Yingxue , Wang Linpeng , Shi Guangxia , Liu Lu , Pei Pei , Guo Jianyou
Published: September 2015

Objective

Acupuncture has been shown to be effective for the treatment of chemotherapy-related nausea and vomiting. The aim of this study was to explore the mechanisms of action underlying the anti-emetic effect of electroacupuncture (EA).

Design

Forty-eight rats received saline (n=12) or 6 mg/kg cisplatin (n=36) to establish a chemotherapy-induced nausea and vomiting model. EA was performed at CV12 (n=12), bilateral PC6 (n=12), or sham points (n=12) 3 days before and 1–2 days after cisplatin administration (4–5 times in total), at 0.5–1 mA intensity and 2/15 Hz frequency for 10 min. Kaolin intake, food intake and bodyweight change were evaluated as markers of nausea and vomiting severity. Concentrations of serotonin (5-hydroxytryptamine, 5-HT) in the duodenum and c-Fos expression in the nucleus of the solitary tract (NTS) were measured using high performance liquid chromatography and immunohistochemistry, respectively.

Results

Cisplatin administration led to increased kaolin intake and reduced food intake and bodyweight over the following 2 days. EA at CV12 significantly reversed the cisplatin-induced change in kaolin intake (on days 1 and 2) and food intake and bodyweight (on day 1). EA at CV12 also attenuated the cisplatin-induced increase in 5-HT in the duodenum and suppressed c-Fos expression in the NTS. EA at PC6 influenced kaolin intake (on day 1 only) and c-Fos expression, but had no statistically significant effect on food intake, bodyweight or 5-HT expression.

Conclusions

This study demonstrated beneficial effects of EA on chemotherapy-induced nausea and vomiting in a rat model. The anti-emetic effect of EA may be mediated through inhibition of 5-HT secretion in the duodenum and activity of the NTS.
Interventions to increase immunisation coverage among children 12–23 months of age in India through participatory learning and community engagement: pilot study for a cluster randomised trial
Authors: Johri Mira , Chandra Dinesh , Koné Georges K , Dudeja Sakshi , Sylvestre Marie-Pierre , Sharma Jitendar K , Pahwa Smriti
Published: September 2015

Objective

With the aim of conducting a future cluster randomised trial to assess intervention impact on child vaccination coverage, we designed a pilot study to assess feasibility and aid in refining methods for the larger study.

Trial design

Cluster-randomised design with a 1:1 allocation ratio.

Methods

Clusters were 12 villages in rural Uttar Pradesh. All women residing in a selected village who were mothers of a child 0–23 months of age were eligible; participants were chosen at random. Over 4 months, intervention group (IG) villages received: (1) home visits by volunteers; (2) community mobilisation events to promote immunisation. Control group (CG) villages received community mobilisation to promote nutrition. A toll-free number for immunisation was offered to all IG and CG village residents. Primary outcomes were ex-ante criteria for feasibility of the main study related to processes for recruitment and randomisation (50% of villages would agree to participate and accept randomisation; 30 women could be recruited in 70% of villages), and retention of participants (50% of women retained from baseline to endline). Clusters were assigned to IG or CG using a computer-generated randomisation schedule. Neither participants nor those delivering interventions were blinded, but those assessing outcomes were blinded to group assignment.

Results

All villages contacted agreed to participate and accepted randomisation. 36 women were recruited per village; 432 participants were randomised (IG n=216; CG n=216). No clusters were lost to follow-up. The main analysis included 86% (373/432) of participants, 90% (195/216) from the IG and 82% (178/216) from the CG.

Conclusions

Criteria related to feasibility were satisfied, giving us confidence that we can successfully conduct a larger cluster randomised trial. Methodological lessons will inform design of the main study.

Trial registration number

ISRCTN16703097
How parents and practitioners experience research without prior consent (deferred consent) for emergency research involving children with life threatening conditions: a mixed method study
Authors: Woolfall Kerry , Frith Lucy , Gamble Carrol , Gilbert Ruth , Mok Quen , Young Bridget ,   the CONNECT advisory group
Published: September 2015

Objective

Alternatives to prospective informed consent to enable children with life-threatening conditions to be entered into trials of emergency treatments are needed. Across Europe, a process called deferred consent has been developed as an alternative. Little is known about the views and experiences of those with first-hand experience of this controversial consent process. To inform how consent is sought for future paediatric critical care trials, we explored the views and experiences of parents and practitioners involved in the CATheter infections in CHildren (CATCH) trial, which allowed for deferred consent in certain circumstances.

Design

Mixed method survey, interview and focus group study.

Participants

275 parents completed a questionnaire; 20 families participated in an interview (18 mothers, 5 fathers). 17 CATCH practitioners participated in one of four focus groups (10 nurses, 3 doctors and 4 clinical trial unit staff).

Setting

12 UK children's hospitals.

Results

Some parents were momentarily shocked or angered to discover that their child had or could have been entered into CATCH without their prior consent. Although these feelings resolved after the reasons why consent needed to be deferred were explained and that the CATCH interventions were already used in clinical care. Prior to seeking deferred consent for the first few times, CATCH practitioners were apprehensive, although their feelings abated with experience of talking to parents about CATCH. Parents reported that their decisions about their child's participation in the trial had been voluntary. However, mistiming the deferred consent discussion had caused distress for some. Practitioners and parents supported the use of deferred consent in CATCH and in future trials of interventions already used in clinical care.

Conclusions

Our study provides evidence to support the use of deferred consent in paediatric emergency medicine; it also indicates the crucial importance of practitioner communication and appropriate timing of deferred consent discussions.
Trends and interaction of polypharmacy and potentially inappropriate prescribing in primary care over 15 years in Ireland: a repeated cross-sectional study
Authors: Moriarty Frank , Hardy Colin , Bennett Kathleen , Smith Susan M , Fahey Tom
Published: September 2015

Objectives

To examine: (1) changes in polypharmacy in 1997, 2002, 2007 and 2012 and; (2) changes in potentially inappropriate prescribing (PIP) prevalence and the relationship between PIP and polypharmacy in individuals aged ≥65 years over this period in Ireland.

Methods

This repeated cross-sectional study using pharmacy claims data included all individuals eligible for the General Medical Services scheme in the former Eastern Health Board region of Ireland in 1997, 2002, 2007 and 2012 (range 338 025–539 752 individuals). Outcomes evaluated were prevalence of polypharmacy (being prescribed ≥5 regular medicines) and excessive polypharmacy (≥10 regular medicines) in all individuals and PIP prevalence in those aged ≥65 years determined by 30 criteria from the Screening Tool for Older Persons’ Prescriptions.

Results

The prevalence of polypharmacy increased from 1997 to 2012, particularly among older individuals (from 17.8% to 60.4% in those aged ≥65 years). The adjusted incident rate ratio for polypharmacy in 2012 compared to 1997 was 4.16 (95% CI 3.23 to 5.36), and for excessive polypharmacy it was 10.53 (8.58 to 12.91). Prevalence of PIP rose from 32.6% in 1997 to 37.3% in 2012. High-dose aspirin and digoxin prescribing decreased over time, but long-term proton pump inhibitors at maximal dose increased substantially (from 0.8% to 23.8%). The odds of having any PIP in 2012 were lower compared to 1997 after controlling for gender and level of polypharmacy, OR 0.39 (95% CI 0.39 to 0.4).

Conclusions

Accounting for the marked increase in polypharmacy, prescribing quality appears to have improved with a reduction in the odds of having PIP from 1997 to 2012. With growing numbers of people taking multiple regular medicines, strategies to address the related challenges of polypharmacy and PIP are needed.
Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial
Authors: Wade Julia , Holding Peter N , Bonnington Susan , Rooshenas Leila , Lane J Athene , Salter C Elizabeth , Tilling Kate , Speakman Mark J , Brewster Simon F , Evans Simon , Neal David E , Hamdy Freddie C , Donovan Jenny L
Published: September 2015

Objectives

To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial.

Design

Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability.

Setting

Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK.

Participants

Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM.

Results

Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care.

Conclusions

The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice.

Trial registration numbers

NCT02044172;ISRCTN20141297.
Improving access to high-quality primary care for socioeconomically disadvantaged older people in rural areas: a mixed method study protocol
Authors: Ford John A , Jones Andrew P , Wong Geoff , Clark Allan B , Porter Tom , Shakespeare Tom , Swart Ann Marie , Steel Nicholas
Published: September 2015

Introduction

The UK has an ageing population, especially in rural areas, where deprivation is high among older people. Previous research has identified this group as at high risk of poor access to healthcare. The aim of this study is to generate a theory of how socioeconomically disadvantaged older people from rural areas access primary care, to develop an intervention based on this theory and test it in a feasibility trial.

Methods and analysis

On the basis of the MRC Framework for Developing and Evaluating Complex Interventions, three methods will be used to generate the theory. First, a realist review will elucidate the patient pathway based on existing literature. Second, an analysis of the English Longitudinal Study of Ageing will be completed using structural equation modelling. Third, 15 semistructured interviews will be undertaken with patients and four focus groups with health professionals. A triangulation protocol will be used to allow each of these methods to inform and be informed by each other, and to integrate data into one overall realist theory. Based on this theory, an intervention will be developed in discussion with stakeholders to ensure that the intervention is feasible and practical. The intervention will be tested within a feasibility trial, the design of which will depend on the intervention. Lessons from the feasibility trial will be used to refine the intervention and gather the information needed for a definitive trial.

Ethics and dissemination

Ethics approval from the regional ethics committee has been granted for the focus groups with health professionals and interviews with patients. Ethics approval will be sought for the feasibility trial after the intervention has been designed. Findings will be disseminated to the key stakeholders involved in intervention development, to researchers, clinicians and health planners through peer-reviewed journal articles and conference publications, and locally through a dissemination event.
UK Fixation of Distal Tibia Fractures (UK FixDT): protocol for a randomised controlled trial of ‘locking’ plate fixation versus intramedullary nail fixation in the treatment of adult patients with a displaced fracture of the distal tibia
Authors: Achten Juul , Parsons Nicholas R , McGuinness Katie R , Petrou Stavros , Lamb Sarah E , Costa Matthew L
Published: September 2015

Introduction

The treatment of displaced, extra-articular fractures of the distal tibia remains controversial. These injuries are difficult to manage due to limited soft tissue cover, poor vascularity of the area and proximity to the ankle joint. Surgical treatment options are expanding and include locked intramedullary nails, plate and screw fixation and external fixator systems. The nail and plate options are most commonly used in the UK, but controversy exists over which treatment is most clinically and cost-effective. In this multicentre randomised controlled trial we aim to assess ratings of disability 6 months postinjury in patients who have sustained a distal tibia fracture treated with either an intramedullary nail or plate and locking screw fixation.

Methods and analysis

Adult patients presenting at trial centres with an acute fracture of the distal tibia will be considered for inclusion. A total of 320 patients will provide 90% power to detect a difference of 8 points in Disability Rating Index (DRI) score at 6 months at the 5% level. The randomisation sequence is stratified by trial centre and age, and administered via web-based service with 1:1 treatment allocation. Baseline demographic and pre-injury functional data and radiographs will be collected using the DRI, Olerud and Molander, and EuroQol EQ-5D questionnaire. Clinical assessment, early complications and radiographs will be recorded at 6–8 weeks. Functional outcome, health-related quality of life and resource use will be collected at 3, 6 and 12 months postoperatively. The main analysis will investigate differences in DRI 6 months postsurgery, between the two treatment groups, on an intention-to-treat basis. Tests will be two-sided and considered to provide evidence for a significant difference if p values are <0.05.

Ethics and dissemination

NRES Committee West-Midlands, 6/11/2012 (ref:12/WM/0340). The results of the trial will be disseminated via peer-reviewed publications and presentations at relevant conferences.

Trial registration number

ISRCTN99771224.