bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Staphylococcus epidermidis Biofilm by Trimethylsilane Plasma Coating
Authors: Ma Yibao , Chen Meng , Jones John E. , Ritts Andrew C. , Yu Qingsong , Sun Hongmin
Published: September 2012

Biofilm formation on implantable medical devices is a major impediment to the treatment of nosocomial infections and promotes local progressive tissue destruction.
Staphylococcus epidermidis
infections are the leading cause of biofilm formation on indwelling devices. Bacteria in biofilms are highly resistant to antibiotic treatment, which in combination with the increasing prevalence of antibiotic resistance among human pathogens further complicates treatment of biofilm-related device infections. We have developed a novel plasma coating technology. Trimethylsilane (TMS) was used as a monomer to coat the surfaces of 316L stainless steel and grade 5 titanium alloy, which are widely used in implantable medical devices. The results of biofilm assays demonstrated that this TMS coating markedly decreased
S. epidermidis
biofilm formation by inhibiting the attachment of bacterial cells to the TMS-coated surfaces during the early phase of biofilm development. We also discovered that bacterial cells on the TMS-coated surfaces were more susceptible to antibiotic treatment than their counterparts in biofilms on uncoated surfaces. These findings suggested that TMS coating could result in a surface that is resistant to biofilm development and also in a bacterial community that is more sensitive to antibiotic therapy than typical biofilms.
Serine-Type Carboxypeptidase KexA of Aspergillus oryzae Has Broader Substrate Specificity than Saccharomyces cerevisiae Kex1 and Is Required for Normal Hyphal Growth and Conidiation
Authors: Morita Hiroto , Tomita Sayako , Maeda Hiroshi , Okamoto Ayako , Yamagata Youhei , Kusumoto Ken-Ichi , Amano Hitoshi , Ishida Hiroki , Takeuchi Michio
Published: September 2012

Aspergillus oryzae
has an ortholog of
Saccharomyces cerevisiae KEX1
, termed
kexA
. A truncated form of KexA protein showed serine-type carboxypeptidase activity and somewhat broader substrate specificity than Kex1 protease. Furthermore, our results indicated that KexA is required for normal growth of
A. oryzae
and that it might be involved in hyphal branching.
Increased Resistance to Multiple Antimicrobials and Altered Resistance Gene Expression in CMY-2-Positive Salmonella enterica following a Simulated Patient Treatment with Ceftriaxone
Authors: Hamilton Russell D. , Hulsebus Holly J. , Akbar Samina , Gray Jeffrey T.
Published: September 2012

Salmonellosis is one of the most common causes of food-borne disease in the United States. Increasing antimicrobial resistance and corresponding increases in virulence present serious challenges. Currently, empirical therapy for invasiveSalmonella entericainfection includes either ceftriaxone or ciprofloxacin (E. L. Hohmann, Clin. Infect. Dis. 32:263–269, 2001). TheblaCMY-2gene confers resistance to ceftriaxone, the antimicrobial of choice for pediatric patients with invasiveSalmonella entericainfections, making these infections especially dangerous (J. M. Whichard et al., Emerg. Infect. Dis. 11:1464–1466, 2005). We hypothesized thatblaCMY-2-positiveSalmonella entericawould exhibit increased MICs to multiple antimicrobial agents and increased resistance gene expression following exposure to ceftriaxone using a protocol that simulated a patient treatmentin vitro. SevenSalmonella entericastrains survived a simulated patient treatmentin vitroand, following treatment, exhibited a significantly increased ceftriaxone MIC. Not only would these isolates be less responsive to further ceftriaxone treatment, but because theblaCMY-2genes are commonly located on large, multidrug-resistant plasmids, increased expression of theblaCMY-2gene may be associated with increased expression of other drug resistance genes located on the plasmid (N. D. Hanson and C. C. Sanders, Curr. Pharm. Des. 5:881–894, 1999). The results of this study demonstrate that a simulated patient treatment with ceftriaxone can alter the expression of antimicrobial resistance genes, includingblaCMY-2andfloRinS. entericaserovar Typhimurium andS. entericaserovar Newport. Additionally, we have shown increased MICs following a simulated patient treatment with ceftriaxone for tetracycline, amikacin, ceftriaxone, and cefepime, all of which have resistance genes commonly located on CMY-2 plasmids. The increases in resistance observed are significant and may have a negative impact on both public health and antimicrobial resistance ofSalmonella enterica.
Impact of Vitamin B
12
on Formation of the Tetrachloroethene Reductive Dehalogenase in Desulfitobacterium hafniense Strain Y51
Authors: Reinhold Anika , Westermann Martin , Seifert Jana , von Bergen Martin , Schubert Torsten , Diekert Gabriele
Published: September 2012

Corrinoids are essential cofactors of reductive dehalogenases in anaerobic bacteria. Microorganisms mediating reductive dechlorination as part of their energy metabolism are either capable of
de novo
corrinoid biosynthesis (e.g.,
Desulfitobacterium
spp.) or dependent on exogenous vitamin B
12
(e.g.,
Dehalococcoides
spp.). In this study, the impact of exogenous vitamin B
12
(cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the subcellular localization of the reductive PCE dehalogenase was investigated in the Gram-positive
Desulfitobacterium hafniense
strain Y51, a bacterium able to synthesize corrinoids
de novo
. PCE-depleted cells grown for several subcultivation steps on fumarate as an alternative electron acceptor lost the tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of the
pce
gene cluster. In the absence of vitamin B
12
, a gradual decrease of the PceA activity and protein amount was observed; after 5 subcultivation steps with 10% inoculum, more than 90% of the enzyme activity and of the PceA protein was lost. In the presence of vitamin B
12
, a significant delay in the decrease of the PceA activity with an ∼90% loss after 20 subcultivation steps was observed. This corresponded to the decrease in the
pceA
gene level, indicating that exogenous vitamin B
12
hampered the transposition of the
pce
gene cluster. In the absence or presence of exogenous vitamin B
12
, the intracellular corrinoid level decreased in fumarate-grown cells and the PceA precursor formed catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate that exogenous vitamin B
12
is not incorporated into the PceA precursor, even though it affects the transposition of the
pce
gene cluster.
Enhancement of Acetic Acid Tolerance in Saccharomyces cerevisiae by Overexpression of the
HAA1
Gene, Encoding a Transcriptional Activator
Authors: Tanaka Koichi , Ishii Yukari , Ogawa Jun , Shima Jun
Published: September 2012

Haa1 is a transcriptional activator required for
Saccharomyces cerevisiae
adaptation to weak acids. Here we show that the constitutive
HAA1
-overexpressing strain acquired a higher level of acetic acid tolerance. Under conditions of acetic acid stress, the intracellular level of acetic acid was significantly lower in
HAA1
-overexpressing cells than in the wild-type cells.
Overexpression of a Novel Biotrophy-Specific Colletotrichum truncatum Effector, CtNUDIX, in Hemibiotrophic Fungal Phytopathogens Causes Incompatibility with Their Host Plants
Authors: Bhadauria Vijai , Banniza Sabine , Vandenberg Albert , Selvaraj Gopalan , Wei Yangdou
Published: September 2012

The hemibiotrophic fungusColletotrichum truncatumcauses anthracnose disease on lentils and a few other grain legumes. It shows initial symptomless intracellular growth, where colonized host cells remain viable (biotrophy), and then switches to necrotrophic growth, killing the colonized host plant tissues. Here, we report a novel effector gene,CtNUDIX, fromC. truncatumthat is exclusively expressed during the late biotrophic phase (before the switch to necrotrophy) and elicits a hypersensitive response (HR)-like cell death in tobacco leaves transiently expressing the effector. CtNUDIX homologs, which contain a signal peptide and a Nudix hydrolase domain, may be unique to hemibiotrophic fungal and fungus-like plant pathogens. CtNUDIX lacking a signal peptide or a Nudix motif failed to induce cell death in tobacco. Expression of CtNUDIX:eGFP in tobacco suggested that the fusion protein might act on the host cell plasma membrane. Overexpression ofCtNUDIXinC. truncatumand the rice blast pathogen,Magnaporthe oryzae, resulted in incompatibility with the hosts lentil and barley, respectively, by causing an HR-like response in infected host cells associated with the biotrophic invasive hyphae. These results suggest thatC. truncatumand possiblyM. oryzaeelicit cell death to signal the transition from biotrophy to necrotrophy.
Campylobacter jejuni Outer Membrane Vesicles Play an Important Role in Bacterial Interactions with Human Intestinal Epithelial Cells
Authors: Elmi Abdi , Watson Eleanor , Sandu Pamela , Gundogdu Ozan , Mills Dominic C. , Inglis Neil F. , Manson Erin , Imrie Lisa , Bajaj-Elliott Mona , Wren Brendan W. , Smith David G. E. , Dorrell Nick
Published: September 2012

Campylobacter jejuni
is the most prevalent cause of food-borne gastroenteritis in the developed world; however, the molecular basis of pathogenesis is unclear. Secretion of virulence factors is a key mechanism by which enteric bacterial pathogens interact with host cells to enhance survival and/or damage the host. However,
C. jejuni
lacks the virulence-associated secretion systems possessed by other enteric pathogens. Many bacterial pathogens utilize outer membrane vesicles (OMVs) for delivery of virulence factors into host cells. In the absence of prototypical virulence-associated secretion systems, OMVs could be an important alternative for the coordinated delivery of
C. jejuni
proteins into host cells. Proteomic analysis of
C. jejuni
11168H OMVs identified 151 proteins, including periplasmic and outer membrane-associated proteins, but also many determinants known to be important in survival and pathogenesis, including the cytolethal distending toxin (CDT).
C. jejuni
OMVs contained 16
N
-linked glycoproteins, indicating a delivery mechanism by which these periplasm-located yet immunogenic glycoproteins can interact with host cells.
C. jejuni
OMVs possess cytotoxic activity and induce a host immune response from T84 intestinal epithelial cells (IECs), which was not reduced by OMV pretreatment with proteinase K or polymyxin B prior to coincubation with IECs. Pretreatment of IECs with methyl-beta-cyclodextrin partially blocks OMV-induced host immune responses, indicating a role for lipid rafts in host cell plasma membranes during interactions with
C. jejuni
OMVs. OMVs isolated from a
C. jejuni
11168H
cdtA
mutant induced interleukin-8 (IL-8) to the same extent as did wild-type OMVs, suggesting OMV induction of IL-8 is independent of CDT.
Global Effect of Interleukin-10 on the Transcriptional Profile Induced by Neisseria meningitidis in Human Monocytes
Authors: Gopinathan Unni , Øvstebø Reidun , Olstad Ole Kristoffer , Brusletto Berit , Dalsbotten Aass Hans Christian , Kierulf Peter , Brandtzaeg Petter , Berg Jens Petter
Published: September 2012

In meningococcal septic shock, the dominant inducer of inflammation is lipopolysaccharide (LPS) in the outer membrane ofNeisseria meningitidis, while interleukin-10 (IL-10) is the principal anti-inflammatory cytokine. We have used microarrays and Ingenuity Pathway Analysis to study the global effects of IL-10 on gene expression induced byN. meningitidis, after exposure of human monocytes (n= 5) for 3 h toN. meningitidis(106cells/ml), recombinant human IL-10 (rhIL-10) (25 ng/ml), andN. meningitidiscombined with rhIL-10.N. meningitidisand IL-10 differentially expressed 3,579 and 648 genes, respectively. IL-10 downregulated 125 genes which were upregulated byN. meningitidis, including NLRP3, the key molecule of the NLRP3 inflammasome. IL-10 also upregulated 270 genes which were downregulated byN. meningitidis, including members of the leukocyte immunuglobulin-like receptor (LIR) family. Fifty-three genes revealed a synergistically increased expression whenN. meningitidisand IL-10 were combined. AIM2 (the principal molecule of the AIM2 inflammasome) was among these genes (fold change [FC], 18.3 versus 7.4 and 9.4 after stimulation byN. meningitidisand IL-10, respectively). We detected reduced concentrations (92% to 40%) of six cytokines (IL-1b, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], macrophage inflammatory protein alpha [MIP-α], MIP-β) in the presence of IL-10, compared with concentrations with stimulation byN. meningitidisalone. Our data analysis of the effects of IL-10 on gene expression induced byN. meningitidissuggests that high plasma levels of IL-10 in meningococcal septic shock plasma may have a profound effect on a variety of functions and cellular processes in human monocytes, including cell-to-cell signaling, cellular movement, cellular development, antigen presentation, and cell death.
Antigenic Characterization of an Intrinsically Unstructured Protein, Plasmodium falciparum Merozoite Surface Protein 2
Authors: Adda Christopher G. , MacRaild Christopher A. , Reiling Linda , Wycherley Kaye , Boyle Michelle J. , Kienzle Vivian , Masendycz Paul , Foley Michael , Beeson James G. , Norton Raymond S. , Anders Robin F.
Published: September 2012

Merozoite surface protein 2 (MSP2) is an abundant glycosylphosphatidylinositol (GPI)-anchored protein ofPlasmodium falciparum, which is a potential component of a malaria vaccine. As all forms of MSP2 can be categorized into two allelic families, a vaccine containing two representative forms of MSP2 may overcome the problem of diversity in this highly polymorphic protein. Monomeric recombinant MSP2 is an intrinsically unstructured protein, but its conformational properties on the merozoite surface are unknown. This question is addressed here by analyzing the 3D7 and FC27 forms of recombinant and parasite MSP2 using a panel of monoclonal antibodies raised against recombinant MSP2. The epitopes of all antibodies, mapped using both a peptide array and by nuclear magnetic resonance (NMR) spectroscopy on full-length recombinant MSP2, were shown to be linear. The antibodies revealed antigenic differences, which indicate that the conserved N- and C-terminal regions, but not the central variable region, are less accessible in the parasite antigen. This appears to be an intrinsic property of parasite MSP2 and is not dependent on interactions with other merozoite surface proteins as the loss of some conserved-region epitopes seen using the immunofluorescence assay (IFA) on parasite smears was also seen on Western blot analyses of parasite lysates. Further studies of the structural basis of these antigenic differences are required in order to optimize recombinant MSP2 constructs being evaluated as potential vaccine components.
The Hydroxamate Siderophore Rhequichelin Is Required for Virulence of the Pathogenic Actinomycete Rhodococcus equi
Authors: Miranda-CasoLuengo Raúl , Coulson Garry B. , Miranda-CasoLuengo Aleksandra , Vázquez-Boland José A. , Hondalus Mary K. , Meijer Wim G.
Published: September 2012

We previously showed that the facultative intracellular pathogen
Rhodococcus equi
produces a nondiffusible and catecholate-containing siderophore (rhequibactin) involved in iron acquisition during saprophytic growth. Here, we provide evidence that the
rhbABCDE
cluster directs the biosynthesis of a hydroxamate siderophore, rhequichelin, that plays a key role in virulence. The
rhbC
gene encodes a nonribosomal peptide synthetase that is predicted to produce a tetrapeptide consisting of
N

5

-formyl-
N
5
-hydroxyornithine, serine,
N
5
-hydroxyornithine, and
N

5

-acyl-
N
5
-hydroxyornithine. The other
rhb
genes encode putative tailoring enzymes mediating modification of ornithine residues incorporated into the hydroxamate product of RhbC. Transcription of
rhbC
was upregulated during growth in iron-depleted medium, suggesting that it plays a role in iron acquisition. This was confirmed by deletion of
rhbCD
, rendering the resulting strain
R. equi
SID2 unable to grow in the presence of the iron chelator 2,2-dipyridyl. Supernatant of the wild-type strain rescued the phenotype of
R. equi
SID2. The importance of rhequichelin in virulence was highlighted by the rapid increase in transcription levels of
rhbC
following infection and the inability of
R. equi
SID2 to grow within macrophages. Unlike the wild-type strain,
R. equi
SID2 was unable to replicate
in vivo
and was rapidly cleared from the lungs of infected mice. Rhequichelin is thus a key virulence-associated factor, although nonpathogenic
Rhodococcus
species also appear to produce rhequichelin or a structurally closely related compound. Rhequichelin biosynthesis may therefore be considered an example of cooption of a core actinobacterial trait in the evolution of
R. equi
virulence.
Escherichia coli Isolates That Carry
vat
,
fyuA
,
chuA
, and
yfcV
Efficiently Colonize the Urinary Tract
Authors: Spurbeck Rachel R. , Dinh Paul C. , Walk Seth T. , Stapleton Ann E. , Hooton Thomas M. , Nolan Lisa K. , Kim Kwang Sik , Johnson James R. , Mobley Harry L. T.
Published: September 2012

Extraintestinal
Escherichia coli
(ExPEC), a heterogeneous group of pathogens, encompasses avian, neonatal meningitis, and uropathogenic
E. coli
strains. While several virulence factors are associated with ExPEC, there is no core set of virulence factors that can be used to definitively differentiate these pathotypes. Here we describe a multiplex of four virulence factor-encoding genes,
yfcV
,
vat
,
fyuA
, and
chuA
, highly associated with uropathogenic
E. coli
strains that can distinguish three groups of
E. coli
: diarrheagenic and animal-associated
E. coli
strains, human commensal and avian pathogenic
E. coli
strains, and uropathogenic and neonatal meningitis
E. coli
strains. Furthermore, human intestinal isolates that encode all four predictor genes express them during exponential growth in human urine and colonize the bladder in the mouse model of ascending urinary tract infection in higher numbers than human commensal strains that do not encode the four predictor genes (
P
= 0.02), suggesting that the presence of the predictors correlates with uropathogenic potential.
Leptospiral Outer Membrane Protein Microarray, a Novel Approach to Identification of Host Ligand-Binding Proteins
Authors: Pinne Marija , Matsunaga James , Haake David A.
Published: September 2012

Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic spirochetes belonging to the genusLeptospira. The leptospiral life cycle involves transmission via freshwater and colonization of the renal tubules of their reservoir hosts. Infection requires adherence to cell surfaces and extracellular matrix components of host tissues. These host-pathogen interactions involve outer membrane proteins (OMPs) expressed on the bacterial surface. In this study, we developed anLeptospira interrogansserovar Copenhageni strain Fiocruz L1-130 OMP microarray containing all predicted lipoproteins and transmembrane OMPs. A total of 401 leptospiral genes or their fragments were transcribed and translatedin vitroand printed on nitrocellulose-coated glass slides. We investigated the potential of this protein microarray to screen for interactions between leptospiral OMPs and fibronectin (Fn). This approach resulted in the identification of the recently described fibronectin-binding protein, LIC10258 (MFn8, Lsa66), and 14 novel Fn-binding proteins, denotedMicroarrayFn-binding proteins (MFns). We confirmed Fn binding of purified recombinant LIC11612 (MFn1), LIC10714 (MFn2), LIC11051 (MFn6), LIC11436 (MFn7), LIC10258 (MFn8, Lsa66), and LIC10537 (MFn9) by far-Western blot assays. Moreover, we obtained specific antibodies to MFn1, MFn7, MFn8 (Lsa66), and MFn9 and demonstrated that MFn1, MFn7, and MFn9 are expressed and surface exposed underin vitrogrowth conditions. Further, we demonstrated that MFn1, MFn4 (LIC12631, Sph2), and MFn7 enable leptospires to bind fibronectin when expressed in the saprophyte,Leptospira biflexa. Protein microarrays are valuable tools for high-throughput identification of novel host ligand-binding proteins that have the potential to play key roles in the virulence mechanisms of pathogens.
Directional Evolution of Chlamydia trachomatis towards Niche-Specific Adaptation
Authors: Borges Vítor , Nunes Alexandra , Ferreira Rita , Borrego Maria J. , Gomes João P.
Published: September 2012

On behalf of the host-pathogen “arms race,” a cutting-edge approach for elucidating genotype-phenotype relationships relies on the identification of positively selected loci involved in pathoadaptation. We studied the obligate intracellular bacterium
Chlamydia trachomatis
, for which same-species strains display a nearly identical core and pan genome, while presenting a wide range of tissue tropism and ecological success. We sought to evaluate the evolutionary patterns underlying species separation (divergence) and
C. trachomatis
serovar radiation (polymorphism) and to establish genotype-phenotype associations. By analyzing 60
Chlamydia
strains, we detected traces of Muller's ratchet as a result of speciation and identified positively selected genes and codons hypothetically involved in the infection of different human cell types (e.g., columnar epithelial cells of ocular or genital mucosae and mononuclear phagocytes) and also events likely driving pathogenic and ecological success dissimilarities. In general, these genes code for proteins involved in immune response elicitation, proteolysis, and the subversion of host-cell functions, and also for proteins with unknown function(s). Several genes are potentially involved in more than one adaptive process, suggesting multiple functions or a distinct
modus operandi
for a specific function, and thus should be considered as crucial research targets. In addition, six of the nine genes encoding the putative antigen/adhesin polymorphic membrane proteins seem to be under positive selection along specific serovars, which sustains an essential biological role of this extra-large paralogue family in chlamydial pathobiology. This study provides insight into how evolutionary inferences illuminate ecological processes such as adaptation to different niches, pathogenicity, or ecological success driven by arms races.
A Conserved UDP-Glucose Dehydrogenase Encoded outside the
hasABC
Operon Contributes to Capsule Biogenesis in Group A Streptococcus
Authors: Cole Jason N. , Aziz Ramy K. , Kuipers Kirsten , Timmer Anjuli M. , Nizet Victor , van Sorge Nina M.
Published: September 2012

Group A
Streptococcus
(GAS) is a human-specific bacterial pathogen responsible for serious morbidity and mortality worldwide. The hyaluronic acid (HA) capsule of GAS is a major virulence factor, contributing to bloodstream survival through resistance to neutrophil and antimicrobial peptide killing and to
in vivo
pathogenicity. Capsule biosynthesis has been exclusively attributed to the ubiquitous
hasABC
hyaluronan synthase operon, which is highly conserved across GAS serotypes. Previous reports indicate that
hasA
, encoding hyaluronan synthase, and
hasB
, encoding UDP-glucose 6-dehydrogenase, are essential for capsule production in GAS. Here, we report that precise allelic exchange mutagenesis of
hasB
in GAS strain 5448, a representative of the globally disseminated M1T1 serotype, did not abolish HA capsule synthesis.
In silico
whole-genome screening identified a putative HasB paralog, designated HasB2, with 45% amino acid identity to HasB at a distant location in the GAS chromosome.
In vitro
enzymatic assays demonstrated that recombinant HasB2 is a functional UDP-glucose 6-dehydrogenase enzyme. Mutagenesis of
hasB2
alone slightly decreased capsule abundance; however, a Δ
hasB
Δ
hasB2
double mutant became completely acapsular. We conclude that HasB is not essential for M1T1 GAS capsule biogenesis due to the presence of a newly identified HasB paralog, HasB2, which most likely resulted from gene duplication. The identification of redundant UDP-glucose 6-dehydrogenases underscores the importance of HA capsule expression for M1T1 GAS pathogenicity and survival in the human host.
Analysis of ThiC Variants in the Context of the Metabolic Network of Salmonella enterica
Authors: Palmer Lauren D. , Dougherty Michael J. , Downs Diana M.
Published: September 2012

In bacteria, the 4-amino-hydroxymethyl-2-methylpyrimidine (HMP) moiety of thiamine is synthesized from 5-aminoimidazole ribotide (AIR), a branch point metabolite of purine and thiamine biosynthesis. ThiC is a member of the radical
S
-adenosylmethionine (AdoMet) superfamily and catalyzes the complex chemical rearrangement of AIR to HMP-P. As reconstituted
in vitro
, the ThiC reaction requires AdoMet, AIR, and reductant. This study analyzed variants of ThiC
in vivo
and
in vitro
to probe the metabolic network surrounding AIR in
Salmonella enterica
. Several variants of ThiC that required metabolic perturbations to function
in vivo
were biochemically characterized
in vitro
. Results presented herein indicate that the subtleties of the metabolic network have not been captured in the current reconstitution of the ThiC reaction.
The Combined Effect of Acupuncture and Tanacetum parthenium on quality of life in women with headache: Randomised study
Authors: Ferro Eliane Cristina , Biagini Angelo Piva , da Silva Ícaro Eduardo Fuchs , Silva Marcelo Lourenço , Silva Josie Resende Torres
Published: September 2012

Background

The aim of the present study was to investigate the efficacy and tolerability of acupuncture (AC), Tanacetum (TAN) or combined treatment on quality of life in women with chronic migraine (CM).

Methods

A total of 69 women volunteers were randomly divided into 3 groups: AC, acupuncture administered in 20 sessions over 10 weeks (n=22); TAN, at 150 mg/day (n=23); and AC+TAN (n=23). The primary outcome was Short-Form 36 (SF-36) quality of life assessment score. Secondary outcomes included the Migraine Disability Assessment (MIDAS) and visual analogue scale (VAS) score experienced after randomisation.

Results

AC+TAN was statistically significantly more effective than AC or TAN alone in overall health-related quality of life (SF-36; p<0.05), on MIDAS score (−35.1 (10.6) AC vs −24.8 (11.7) TAN vs −42.5 (9.8) AC+TAN; p<0.05) and in reducing the mean score of pain on VAS (−5.6 (2.4) AC vs −3.7 (2.1) TAN vs −6.4 (3.1) AC+TAN; p<0.05).

Conclusions

The present work shows an improvement of the quality of life and better analgesic effect of acupuncture combined with TAN treatment on migraine pain in women when compared with acupuncture or TAN alone.
Epilepsies in infancy
Authors: Alam Shouja , Lux Andrew L
Published: September 2012

To evaluate and manage epileptic seizures and other paroxysmal events in infants, it is necessary to ask five key questions: (1) Is this a type of epilepsy?; (2) What seizure type(s) are occurring?; (3) Do these seizure types, combined with factors such as age at onset and EEG features, constitute an ‘epilepsy syndrome’?; (4) What investigations do we need to do in searching for an underlying aetiology? and finally, (5) What is the prognosis for neurological and developmental state in later life?

This review considers epilepsies that have an onset in infancy but after the perinatal period, outlines the commoner epilepsy syndromes occurring in this age group and describes paroxysmal events that can mimic epilepsy. Epilepsies in infancy may be the manifestation of a genetic predisposition associated with a benign course and good prognosis for neurodevelopment. In contrast, they may pose the challenging situation of ‘epileptic encephalopathy’, rare but potentially treatable metabolic conditions, or structural abnormalities with poor developmental outlook and intractable seizures. Seizures in infancy are relatively rare and there is a wide range of underlying causes, some of which require specific treatments to avoid preventable neurodevelopmental damage. Guidance from the National Institute for Health and Clinical Excellence suggests early referral of cases of infantile epilepsy to a tertiary centre.
Brain drain in sub-Saharan Africa: contributing factors, potential remedies and the role of academic medical centres
Authors: Kasper Jennifer , Bajunirwe Francis
Published: September 2012

A double jeopardy exists in resource-limited settings (RLS) in sub-Saharan Africa (SSA): there are a disproportionately greater number of acutely ill patients, but a paucity of healthcare workers (HCW) to care for them. SSA has 25% of the global disease burden but only 3% of the world's HCW. Thirty-two SSA countries do not meet the WHO minimum of 23 HCW per 10000 population. Contributing factors include insufficient supply, inadequate distribution and migration. Potential remedies include international workforce policies, non-governmental organisations, national and international medical organisations’ codes of conduct, inter-country collaborations, donor-directed policies and funding to train more people in-country, and health system strengthening and task-shifting. Collaborations among academic institutions from resource-rich and poor countries can help address HCW supply, distribution and migration. It is now opportune to harness bright, committed people from academic centres in resource-rich and poor settings to create long-term, collaborative relationships focused on training, clinical skills and locally relevant research endeavours, who mutually strive for HCW retention, less migration, and ultimately sufficient HCW to provide optimal care in all RLS.
Are boys and girls that different? An analysis of traumatic brain injury in children
Authors: Collins Niamh C , Molcho Michal , Carney Peter , McEvoy Linda , Geoghegan Lourda , Phillips Jack P , Nicholson Alf J
Published: September 2012

Introduction

The Phillips Report on traumatic brain injury (TBI) in Ireland found that injury was more frequent in men and that gender differences were present in childhood. This study determined when gender differences emerge and examined the effect of gender on the mechanism of injury, injury type and severity and outcome.

Methods

A national prospective, observational study was conducted over a 2-year period. All patients under 17 years of age referred to a neurosurgical service following TBI were included. Data on patient demographics, events surrounding injury, injury type and severity, patient management and outcome were collected from ‘on-call’ logbooks and neurosurgical admissions records.

Results

342 patients were included. Falls were the leading cause of injury for both sexes. Boys’ injuries tended to involve greater energy transfer and involved more risk-prone behaviour resulting in a higher rate of other (non-brain) injury and a higher mortality rate. Intentional injury occurred only in boys. While injury severity was similar for boys and girls, significant gender differences in injury type were present; extradural haematomas were significantly higher in boys (p=0.014) and subdural haematomas were significantly higher in girls (p=0.011). Mortality was 1.8% for girls and 4.3% for boys.

Conclusions

Falls were responsible for most TBI, the home is the most common place of injury and non-operable TBI was common. These findings relate to all children. Significant gender differences exist from infancy. Boys sustained injuries associated with a greater energy transfer, were less likely to use protective devices and more likely to be injured deliberately. This results in a different pattern of injury, higher levels of associated injury and a higher mortality rate.
Deliberate self-harm patients in the emergency department: who will repeat and who will not? Validation and development of clinical decision rules
Authors: Bilén Katarina , Ponzer Sari , Ottosson Carin , Castrén Maaret , Pettersson Hans
Published: September 2012

Objectives

(1) Validate an existing clinical tool for assessing risk after deliberate self-harm (DSH), Manchester Self-Harm Rule, in a new setting and new population, (2) develop a clinical decision rule based on factors associated with repeated self-harm in a Swedish population and (3) compare these rules.

Design

A consecutive series of 1524 patients attending one of Scandinavia's largest emergency departments (ED) due to DSH during a 3-year period were included. Explanatory factors were collected from hospital charts and national databases. A nationwide register-based follow-up of new DSH episode or death by suicide within 6 months was used. We used logistic regression, area under the curve and classification trees to identify factors associated with repetition. To evaluate the ability of different decision rules to identify patients who will repeat DSH, we calculated the sensitivity and specificity.

Main outcome measure

Repeated DSH or suicide within 6 months.

Results

The cumulative incidence for patients repeating within 6 months was 20.3% (95% CI 18.0% to 22.0%). Application of Manchester Self-Harm Rule to our material yielded a sensitivity of 89% and a specificity of 21%. The clinical decision rule based on four factors associated with repetition in the Swedish population yielded a sensitivity of 90% and a specificity of 18%.

Conclusions

Application of either rules, with high sensitivity, may facilitate assessment in the ED and help focus right resources on patients at a higher risk. Irrespective of the choice of decision rule, it is difficult to separate those who will repeat from those who will not due to low specificity.
Sensitive troponin assay predicts outcome in syncope
Authors: Reed Matthew J , Mills Nicholas L , Weir Christopher J
Published: September 2012

Aims

To assess whether plasma troponin concentration measured by a sensitive assay can predict 1-month and 1-year serious outcome, or all-cause death in patients presenting with syncope to the emergency department (ED).

Methods

Prospective cohort study of admitted adult patients presenting to the ED after an episode of syncope who had plasma troponin measured 12 h after syncope using the ARCHITECTSTATsensitive troponin I assay (Abbott Diagnostics). Primary endpoints were the composite endpoint of serious outcome or all-cause death at 1 month and 1 year.

Results

Between 1 March 2007 and 22 July 2008, 338 of 528 patients admitted from the ED with syncope had plasma troponin concentrations determined. Troponin concentrations were above the limit of detection in 261 (77%) patients. Patients numbering 120 (36%) had a troponin concentration ≥0.03 ng/ml (99th percentile of normal reference population), and 66 (20%) had concentrations ≥0.05 ng/ml (local diagnostic threshold for myocardial infarction). The proportion of patients with a composite serious outcome increased across patients stratified into quintiles based on peak troponin concentration at 1 month (0%, 9%, 13%, 26%, 70%) and at 1 year (10%, 22%, 26%, 52%, 85%).

Conclusions

The majority of patients admitted from the ED with syncope have detectable plasma troponin concentrations. Peak troponin concentration was associated with increasing risk of serious outcome and death, and this risk increases with higher troponin concentrations. Troponin may have a future role in the risk stratification of patients with syncope.
Vitamin D deficiency in children presenting to the emergency department: a growing concern. Vitamin D deficiency in Birmingham's children: presentation to the emergency department
Authors: Kehler Lisa , Verma Sapna , Krone Ruth , Roper Emily
Published: September 2012

Introduction

The increase in detected vitamin D deficiency appears to be multifactorial: an increasingly multicultural society, reduced exposure to sunlight due to concern about skin cancer and a more sedentary lifestyle and dietary changes within the population.

Methods

This was a retrospective survey of children found to be vitamin D deficient after attending the emergency department from March 2009 until March 2010. These data were then subdivided according to their age, ethnic origin, presenting complaint and biochemical associated features.

Results

We identified 89 patients with a low vitamin D level (total vitamin D levels less than 50 nmol/l), with 83% of those having very low vitamin D levels (less than 25 nmol/l). The most common presenting features were abdominal pain (19%), a seizure (17%) and limb pain (15%). The most common ethnic origins in our series were Pakistani (37%) followed by black African (11.2%).

Conclusions

Vitamin D deficiency should be considered in children with pigmented skin presenting with a range of symptoms. The detected vitamin D deficiency probably represents only a very small proportion of the vitamin D deficiency in children in Birmingham.
A re-conceptualisation of acute spinal care
Authors: Hauswald Mark
Published: September 2012

The emergency care of patients who may have spinal injuries has become highly ritualised. There is little scientific support for many of the recommended interventions and there is evidence that at least some methods now used in the field and emergency department are harmful. Since prospective clinical trials are not likely to resolve these issues I propose a reconceptualisation of spinal trauma to allow a more rational approach to treatment. To do this I analyse the basic physics, biomechanics and physiology involved. I then develop a list of recommended treatment variations that are more in keeping with the actual causes of post impact neurological deterioration than are current methods. Discarding the fundamentally flawed emphasis on decreasing post injury motion and concentrating on efforts to minimise energy deposition to the injured site, while minimising treatment delays, can simplify and streamline care without subjecting patients to procedures that are not useful and potentially harmful. Specific treatments that are irrational and which can be safely discarded include the use of backboards for transportation, cervical collar use except in specific injury types, immobilisation of ambulatory patients on backboards, prolonged attempts to stabilise the spine during extrication, mechanical immobilisation of uncooperative or seizing patients and forceful in line stabilisation during airway management.
Psychosocial characteristics associated with frequent physical fighting: findings from the 2009 National Youth Risk Behavior Survey
Authors: Swahn Monica H , Bossarte Robert M , Palmier Jane B , Yao Huang , Van Dulmen Manfred H M
Published: September 2012

The goal of the current study was to determine the prevalence and psychosocial correlates associated with frequent fighting among US high school students. Cross-sectional analyses were conducted using the 2009 Youth Risk Behavior Survey (N=16 410). Multivariate logistic regression analyses determined associations between demographic and psychosocial correlates of frequent fighting. Among students, 13.6% reported fighting once, 15.3% reported fighting 2–11 times and 2.6% reported fighting 12 or more times in the past year. Risk factors associated with frequent fighting were weapon carrying (adjusted OR=10.55; 95% CI 7.40 to 15.05), suicide attempt (adjusted OR=6.16; 95% CI 3.70 to 10.28), binge drinking (adjusted OR=3.15; 95% CI 2.16 to 4.59) and feeling too unsafe to go to school (adjusted OR=3.09; 95% CI 2.00 to 4.77). There is a clear need to better understand the patterns and psychosocial characteristics of frequent physical fighting and the prevention and interventions strategies that may be most relevant for these vulnerable youth.
A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies
Authors: Gounis Matthew J , Nogueira Raul G , Mehra Manik , Chueh Juyu , Wakhloo Ajay K
Published: September 2012

Background and purpose

Recanalization strategies mediated by intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective treatment approach than either therapy used alone. There are few preclinical animal models to evaluate these strategies. Here we report on a model to simultaneously evaluate both of these treatment approaches.

Methods

Allogeneic clot was injected through the 6 F guide catheter after creating >50% luminal stenosis of the common carotid arteries of New Zealand White rabbits. The stenosis was released after 1 h, allowing sufficient time for clot–vessel wall interaction. Occlusion was confirmed and each vessel was assigned to receive either balloon angioplasty alone, intra-arterial tissue plasminogen activator (tPA, Alteplase, Genentech, San Francisco, California, USA), tPA delivery through prototype balloon infusion wire (NIT Therapeutics, Pittsburgh,  Pennsylvania, USA), partial stent deployment or partial stent deployment with locally delivered tPA. The negative control received no treatment.

Results

In vivo revascularization Thrombolysis in Cerebral Infarction (TICI) score revealed that the balloon infusion wire achieved a stable and higher revascularization score of TICI 2B, with a lower dose of tPA in comparison with other treatment strategies. All treatment strategies resulted in endothelial denudation and exposure of the internal elastic lamina.

Conclusions

The proposed animal model permits reliable and consistent thromboembolic occlusion of the target vasculature and allows for an assessment of both pharmacologic and mechanical revascularization strategies for acute ischemic stroke.
Changes in high-risk sexual behaviour among Estonian adults between 1996 and 2006
Authors: Liivlaid Hedi , Uusküla Anneli
Published: September 2012

Objective

To describe and compare sexual behaviour patterns in 1996 (before the explosion of the HIV epidemic in 2000) and 2006, and the correlates of high-risk sexual behaviour in Estonia.

Methods

Data on selected sexual behaviour characteristics were obtained by interviewing a probability sample of the adult population in Estonia in 1996 and 2006.

Results

Data were available from 2441 sexually experienced women and 1994 men, and 3005 women and 2812 men in the year 2006. There were no changes in the proportion of sexually experienced adults, frequency of intercourse, or same gender sexual relationships. There was an increase in sex under the age of 16 (women: 8.4% vs 14.1% adjusted OR (AOR) 2.05 (1.67 to 2.53); men: 21.9% vs 28.0% AOR 1.58 (1.35 to 1.84)). From 1996 to 2006, the proportion reporting intercourse with a casual partner in the previous 12 months decreased significantly for women (10.7% vs 6.0% AOR 0.54 (95% CI 0.41 to 0.72)) and men, (24.0% vs 16.5% AOR 0.71 (0.59 to 0.85)) in parallel with a decrease in those reporting never using condoms during intercourse with a casual partner (for women: 49.3% vs 19.2% AOR 0.27 (0.14 to 0.51); and men: 35.4% vs 20.2% AOR 0.37 (0.25 to 0.56)). In 2006, the odds for not always using condoms in intercourse with casual partners increased significantly with age (eg, ≤24 vs ≥45: AOR 3.46 (1.68 to 7.13)), and were higher among those widowed/divorced/separated (AOR 2.35 (CI 1.20 to 4.60)).

Conclusions

From 1996 to 2006, a significant reduction in high-risk sexual behaviour has occurred in Estonia across all age groups and genders.
AXELROD MODEL OF SOCIAL INFLUENCE WITH CULTURAL HYBRIDIZATION
Authors: RADILLO-DÍAZ ALEJANDRO , PÉREZ LUIS A. , DEL CASTILLO-MUSSOT MARCELO
Published: September 2012

Since cultural interactions between a pair of social agents involve changes in both individuals, we present simulations of a new model based on Axelrod's homogenization mechanism that includes hybridization or mixture of the agents' features. In this new hybridization model, once a cultural feature of a pair of agents has been chosen for the interaction, the average of the values for this feature is reassigned as the new value for both agents after interaction. Moreover, a parameter representing social tolerance is implemented in order to quantify whether agents are similar enough to engage in interaction, as well as to determine whether they belong to the same cluster of similar agents after the system has reached the frozen state. The transitions from a homogeneous state to a fragmented one decrease in abruptness as tolerance is increased. Additionally, the entropy associated to the system presents a maximum within the transition, the width of which increases as tolerance does. Moreover, a plateau was found inside the transition for a low-tolerance system of agents with only two cultural features.
NANOSCALE SUPERCONDUCTIVITY
Authors: KRUCHININ S. P. , NAGAO H.
Published: September 2012

We deal with the problem of nanoscale superconductivity. Nanoscale superconductivity remains to be one of the most interesting research areas in condensed mater. Recent technology and experiments have fabricated high-quality superconducting MgB 2 nanoparticles. We consider the two-band superconductivity in ultrasmall grains, by extending the Richardson exact solution to two-band systems, and develop the theory of interactions between nano-scale ferromagnetic particles and superconductors. The properties of nano-sized two-gap superconductors and the Kondo effect in superconducting ultrasmall grains are investigated as well. The theory of the Josephson effect is presented, and his application to quantum computing are analyzed.
MONITORING POWER CONSUMPTION USING A GENERALIZED VARIANT OF SELF-ORGANIZING MAP (SOM)
Authors: ALONSO SERAFÍN , MORÁN ANTONIO , PRADA MIGUEL A. , BARRIENTOS PABLO , DOMÍNGUEZ MANUEL
Published: September 2012

In this paper, we present a new approach for monitoring power consumption in several processes. The generalization of the envSOM algorithm, a variant of Self-Organizing Map (SOM), is used to build an electrical model and visualize the information. The envSOM extended to n hierarchical phases allows us to obtain a more accurate model from real past data. The model is conditioned hierarchically on environmental variables. In this way, time variables can be used to consider seasonality and weekday/hour periodicity. Time variable maps and electrical component planes make it possible to visualize and analyze power consumption. The representation of the Best Matching Unit (BMU) or its trajectory on these maps enables the on-line monitoring.
CONTROL OF SYNCHRONIZATION IN DELAY-COUPLED NETWORKS
Authors: SCHÖLL E. , SELIVANOV A. , LEHNERT J. , DAHMS T. , HÖVEL P. , FRADKOV A.
Published: September 2012

We consider synchronization in networks of delay-coupled oscillators. In these systems, the coupling phase has been found to be a crucial control parameter. By proper choice of this parameter one can switch between different synchronous oscillatory states of the network, e.g., in-phase oscillation, splay or various cluster states. Applying the speed-gradient method, we derive an adaptive algorithm for an automatic adjustment of the coupling phase, coupling strength, and delay time such that a desired state can be selected from an otherwise multistable regime.
NOISE AND OSCILLATIONS IN BIOLOGICAL SYSTEMS: MULTIDISCIPLINARY APPROACH BETWEEN EXPERIMENTAL BIOLOGY, THEORETICAL MODELLING AND SYNTHETIC BIOLOGY
Authors: ULLNER E. , ARES S. , MORELLI L. G. , OATES A. C. , JÜLICHER F. , NICOLA E. , HEUSSEN R. , WHITMORE D. , BLYUSS K. , FRYETT M. , ZAKHAROVA A. , KOSESKA A. , NENE N. R. , ZAIKIN A.
Published: September 2012

Rapid progress of experimental biology has provided a huge flow of quantitative data, which can be analyzed and understood only through the application of advanced techniques recently developed in theoretical sciences. On the other hand, synthetic biology enabled us to engineer biological models with reduced complexity. In this review we discuss that a multidisciplinary approach between this sciences can lead to deeper understanding of the underlying mechanisms behind complex processes in biology. Following the mini symposia "Noise and oscillations in biological systems" on Physcon 2011 we have collected different research examples from theoretical modeling, experimental and synthetic biology.
ON LINEAR MULTI-INPUT SYSTEMS DEPENDING ON CONTINUOUS PARAMETERS. FEEDBACK EQUIVALENCES IN LOW DIMENSION
Authors: CARRIEGOS M. V. , GARCÍA-FERNÁNDEZ R. M. , LÓPEZ-CABECEIRA M. M. , TROBAJO M. T.
Published: September 2012

We survey some recent results relating different notions of feedback equivalence of linear systems in a geometric point of view.