bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Reproductive Immunology to Improve Clinical Practices
Authors: Garg Manish
Published: April 2013

The American Society for Reproductive Immunology's Second Clinical Reproductive Immunology Symposium: ‘Using Reproductive Immunology to Improve Clinical Practices’ was held on October 27th to 28th 2012, in New Haven, Connecticut. The objective of this symposium was to disseminate up‐to‐date clinical reproductive immunology information and how it relates to current clinical practices, diagnostics, and therapeutics for women's reproductive and pregnancy‐related issues, with a view to bridging the distance between clinicians and translational researchers. It provided a common platform to physicians and physician scientists to facilitate the application of research outcomes into current medical practice. This symposium highlighted the current status of health issues during pregnancy including preeclampsia, preterm birth, maternal obesity and diabetes, autoimmunity and infection. In addition, a session was dedicated toward demystifying laboratory techniques of reproductive immunology for clinicians. This symposium was attended by approximately 50 delegates along with the 16 invited speakers and included 17 presentations that addressed key issues in the immunology of maternal–fetal well‐being. This report will summarize the highlights of the meeting.
Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein–Barr virus, and clonality are important predictors of disease progression and regression
Authors: Ichikawa Ayako , Arakawa Fumiko , Kiyasu Junichi , Sato Kensaku , Miyoshi Hiroaki , Niino Daisuke , Kimura Yoshizo , Takeuchi Masanori , Yoshida Maki , Ishibashi Yukinao , Nakashima Shinji , Sugita Yasuo , Miura Osamu , Ohshima Koichi
Published: April 2013

Objectives

Patients with rheumatoid arthritis (RA) may develop lymphoproliferative disorders (RA‐LPD). Immunosuppressive states due to methotrexate (MTX) and Epstein–Barr virus (EBV) reactivation have been regarded as causes. Sometimes spontaneous regression occurs after withdrawal of MTX. The objective of this study was to identify factors predictive of relapse and survival in patients with RA‐LPD, and spontaneous regression in patients with RA‐LPD treated with MTX (MTX‐LPD).

Methods

We evaluated the clinicopathological features, clinical characteristics, and treatment outcomes in 102 cases of RA‐LPD. In addition, EBV infection and clonality of immunoglobulin heavy chain gene (IGH) were analyzed by in situ hybridization and polymerase chain reaction, respectively.

Results

The 102 cases included patients with diffuse large B‐cell lymphoma (DLBCL; n = 53), Hodgkin lymphoma (n = 9), polymorphic B‐cell LPD (n = 20), reactive lymphadenitis (n = 11), peripheral T‐cell lymphoma (PTCL; n = 4), composite lymphoma (n = 2), and follicular lymphoma (n = 3). EBV was detected in 60% (56/93) of patients. Spontaneous regression occurred in 59% (28/47) of patients in whom MTX was withdrawn. Regression was associated with EBV positivity (P = 0.007) and non‐DLBCL (P = 0.006), but not with MTX amount and other clinical features. Monoclonal bands of IGH were observed in 31 of 74 cases. In patients with DLBCL, poor disease‐free survival (P = 0.05) was associated with clonality of IGH. In all patients, factors predictive of shorter survival were age (>70 yr) and histological type of DLBCL.

Conclusions

Histology, EBV positivity, and monoclonality of IGH are useful for predicting clinical outcomes in patients with RA‐LPD.
Recent progress in satellite cell/myoblast engraftment – relevance for therapy
Authors: Briggs Deborah , Morgan Jennifer E.
Published: April 2013

There is currently no cure for muscular dystrophies, although several promising strategies are in basic and clinical research. One such strategy is cell transplantation with satellite cells (or their myoblast progeny) to repair damaged muscle and provide dystrophin protein with the aim of preventing subsequent myofibre degeneration and repopulating the stem cell niche for future use. The present review aims to cover recent advances in satellite cell/myoblast therapy and to discuss the challenges that remain for it to become a realistic therapy.
Rapid screening of yeast mutants with reporters identifies new splicing phenotypes
Authors: Dreumont Natacha , Séraphin Bertrand
Published: April 2013

Nuclear precursor mRNA splicing requires the stepwise assembly of a large complex, the spliceosome. Recent large‐scale analyses, including purification of splicing complexes, high‐throughput genetic screens and interactomic studies, have linked numerous factors to this dynamic process, including a well‐defined core conserved from yeast to human. Intriguingly, despite extensive studies, no splicing defects were reported for some of the corresponding yeast mutants. To resolve this paradox, we screened a collection of viable yeast strains carrying mutations in splicing‐related factors with a set of reporters including artificial constructs carrying competing splice sites. Previous analyses have indeed demonstrated that this strategy identifies yeast factors able to regulate alternative splicing and whose properties are conserved in human cells. The method, sensitive to subtle defects, revealed new splicing phenotypes for most analyzed factors such as the Urn1 protein. Interestingly, a mutant of PRP8 specifically lacking an N‐terminal proline‐rich region stimulated the splicing of a reporter containing competing branchpoint/3′ splice site regions. Thus, using appropriate reporters, yeast can be used to quickly delineate the effect of various factors on splicing and identify those with the propensity to regulate alternative splicing events.

Structured digital abstract

Lsm8 physically interacts with Prp4, Prp24, Prp3, Prp6, Snu114, Brr2, Lsm4 and Prp8 by tandem affinity purification (View interaction)
Quality of life and satisfaction of patients after nonsurgical primary root canal treatment provided by undergraduate students, graduate students and endodontic specialists
Authors: Hamasha A. A. , Hatiwsh A.
Published: April 2013

Aim

(i) To assess the impact of primary root canal treatment on the perceived quality of life amongst a cohort of Jordanian patients, (ii) to assess this cohort's satisfaction of their primary root canal treatment, and (iii) to evaluate the association of the level of training and experience of clinicians with these two parameters.

Methodology

A systematic random sample of 302 subjects was selected from patients who attended undergraduate, graduate and specialty clinics of Jordan University of Science and Technology. Participants were interviewed before and two weeks after completion of root canal treatment. The study instrument included the Oral Health Impact Profile questionnaire (Dugas et al. 2002) and seven semantic differential scales. Data analyses included descriptive statistics and nonparametric analyses.

Results

More than 90% of subjects reported improvements in the sense of taste, pain, eating, altering food temperature, self‐consciousness, waking up during sleep, interruption of meals, difficulty to relax and difficulty to sleep after root canal treatment. There was no significant difference in terms of improvement amongst patients treated by specialists, graduate students or undergraduate students. The overall semantic differential score of intraoperative pain, pleasantness, chewing ability and general satisfaction was about 8. Satisfaction of root canal treatment by specialists was higher in terms of time involved, intraoperative pain, pleasantness and general satisfaction than those treatments by undergraduate students. Patients treated by specialist were least satisfied with the treatment cost compared to those patients treated by graduate or undergraduate students.

Conclusions

The impact of root canal treatment on the quality of life was apparent. Satisfaction with root canal treatment approximates 8 on the semantic differential scale with preference for specialists over dental students.
The Sensitivity of Overall Collapse of Damaged Submarine Pressure Hulls to Material Strength
Authors: MacKay John R. , Keulen Fred van
Published: April 2013

Budget and schedule restrictions sometimes require naval submarines to be operated with unrepaired corrosion damage to the pressure hull. It is important to understand the effects of corrosion wastage on the structural capacity of the hull, so that appropriate diving depth restrictions can be imposed if necessary. The current paper presents an experimental study of the interaction of material behavior with corrosion defects, especially with respect to their effect on overall elasto-plastic collapse of pressure hulls. Twenty ring-stiffened cylinders, representative of submarine pressure hulls failing by overall collapse, were machined from high- and low-grade aluminum alloy tubes. Artificial general corrosion damage was introduced in selected specimens by machining away material from the outside of the cylinder shell in rectangular patches of uniform depth. The cylinders were monotonically loaded to collapse under external hydrostatic pressure. One corroded cylinder was repeatedly loaded past the yield limit before the collapse test in order to study the effect of cyclic plastic loading on its ultimate collapse strength. Overall collapse pressures for corroded cylinders with a variety of patch sizes and depths and material strengths were reduced by, on average, 0.85 times the depth of thinning divided by the original shell thickness. The collapse strength of corroded cylinders was found to be more sensitive to the shape of the stress-strain curve than for intact specimens. Higher levels of strain hardening and ductility were found to improve the performance of damaged cylinders. Permanent deformations in the cyclically loaded cylinder, as measured with strain gauges, grew with each constant-amplitude load cycle; however, the additional deformations tended towards zero with increasing number of cycles, and a subsequent collapse test indicated that the cyclic loading did not affect the collapse pressure. The sensitivity of overall collapse to material strength is related to not only the yield stress, but also the plastic reserve of the material; higher levels of strain hardening and ductility increase overall collapse strength of hulls, especially those with general corrosion damage. The effect of a given level of corrosion thinning is less severe for cylinders with relatively greater levels of strain hardening. It is unlikely that cyclic plastic loading of corroded hulls will lead to premature collapse at a load level below the monotonic collapse pressure.
Growth Media Simulating Ileal and Colonic Environments Affect the Intracellular Proteome and Carbon Fluxes of Enterohemorrhagic Escherichia coli O157:H7 Strain EDL933
Authors: Polzin Sabrina , Huber Claudia , Eylert Eva , Elsenhans Ines , Eisenreich Wolfgang , Schmidt Herbert
Published: April 2013

In this study, the intracellular proteome of
Escherichia coli
O157:H7 strain EDL933 was analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight (MALDI-TOF) spectrometry after growth in simulated ileal environment media (SIEM) and simulated colonic environment media (SCEM) under aerobic and microaerobic conditions. Differentially expressed intracellular proteins were identified and allocated to functional protein groups. Moreover, metabolic fluxes were analyzed by isotopologue profiling with [U-
13
C
6
]glucose as a tracer. The results of this study show that EDL933 responds with differential expression of a complex network of proteins and metabolic pathways, reflecting the high metabolic adaptability of the strain. Growth in SIEM and SCEM is obviously facilitated by the upregulation of nucleotide biosynthesis pathway proteins and could be impaired by exposition to 50 ï¿½M 6-mercaptopurine under aerobic conditions. Notably, various stress and virulence factors, including Shiga toxin, were expressed without having contact with a human host.
Characterization of
bla
SHV
Genes on Plasmids from Escherichia coli and Salmonella enterica Isolates from Canadian Food Animals (2006-2007)
Authors: Pouget Jennie G. , Coutinho Fiona J. , Reid-Smith Richard J. , Boerlin Patrick
Published: April 2013

bla
SHV
genes from
Escherichia coli
and
Salmonella enterica
isolates from chicken (
n
= 19) and pork (
n
= 1) were identified as
bla
SHV-2
(
n
= 5) or
bla
SHV-2a
(
n
= 15). Eighteen were on plasmids of the incI1 (
n
= 15), incP (
n
= 2), and incFIB (
n
= 1) incompatibility groups. These plasmids were all transferable by conjugation between
E. coli
and
S. enterica
.
Use of Antibody Responses against Locus of Enterocyte Effacement (LEE)-Encoded Antigens To Monitor Enterohemorrhagic Escherichia coli Infections on Cattle Farms
Authors: Joris Maria-Adelheid , Vanrompay Daisy , Verstraete Karen , De Reu Koen , De Zutter Lieven , Cox Eric
Published: April 2013

Enterohemorrhagic
Escherichia coli
(EHEC) is a significant zoonotic pathogen causing severe disease associated with watery and bloody diarrhea, hemorrhagic colitis, and the hemolytic-uremic syndrome (HUS) in humans. Infections are frequently associated with contact with EHEC-contaminated ruminant feces. Both natural and experimental infection of cattle induces serum antibodies against the LEE-encoded proteins intimin, EspA, EspB, and Tir and the Shiga toxins Stx1 and Stx2, although the latter are poorly immunogenic in cattle. We determined whether antibodies and/or the kinetics of antibody responses against intimin, Tir, EspA, and/or EspB can be used for monitoring EHEC infections in beef cattle herds in order to reduce carcass contamination at slaughter. We examined the presence of serum antibodies against recombinant O157:H7
E. coli
intimin EspA, EspB, and Tir during a cross-sectional study on 12 cattle farms and during a longitudinal time course study on two EHEC-positive cattle farms. We searched for a possible correlation between intimin, Tir, EspA, and/or EspB antibodies and fecal excretion of EHEC O157, O145, O111, O103, or O26 seropathotypes. The results indicated that serum antibody responses to EspB and EspA might be useful for first-line screening at the herd level for EHEC O157, O26, and most likely also for EHEC O103 infections. However, antibody responses against EspB are of less use for monitoring individual animals, since some EHEC-shedding animals did not show antibody responses and since serum antibody responses against EspB could persist for several months even when shedding had ceased.
Diversity of Benzylsuccinate Synthase-Like (
bssA
) Genes in Hydrocarbon-Polluted Marine Sediments Suggests Substrate-Dependent Clustering
Authors: Acosta-Gonzï¿½lez Alejandro , Rossellï¿½-Mï¿½ra Ramon , Marquï¿½s Silvia
Published: April 2013

The potential of hydrocarbon biodegradation in marine sediments was determined through the detection of a functional biomarker, the
bssA
gene, coding for benzylsuccinate synthase, the key enzyme of anaerobic toluene degradation. Eight
bssA
clone libraries (409 sequences) were constructed from polluted sediments affected by the
Prestige
oil spill in the Atlantic Islands National Park and from hydrocarbon-amended sediment microcosms in Mallorca. The amplified products and database-derived
bssA
-like sequences grouped into four major clusters, as determined by phylogenetic reconstruction, principal coordinate analysis (PCoA), and a subfamily prediction tool. In addition to the classical
bssA
sequences that were targeted, we were able to detect sequences homologous to the naphthylmethylsuccinate synthase gene (
nmsA
) and the alkylsuccinate synthase gene (
assA
), the
bssA
homologues for anaerobic 2-methylnaphthalene and alkane degradation, respectively. The detection of
bssA
-like variants was determined by the persistence and level of pollution in the marine samples. The observed level of gene diversity was lower in the Mallorca sediments, which were dominated by
assA
-like sequences. In contrast, the Atlantic Islands samples, which were highly contaminated with methylnaphthalene-rich crude oil, showed a high proportion of
nmsA
-like sequences. Some of the detected genes were phylogenetically related to
Deltaproteobacteria
communities, previously described as the predominant hydrocarbon degraders at these sites. Differences between all detected
bssA
-like genes described to date indicate separation between marine and terrestrial sequences and further subgrouping according to taxonomic affiliation. Global analysis suggested that
bssA
homologues appeared to cluster according to substrate specificity. We observed undetected divergent gene lineages of
bssA
homologues, which evidence the existence of new degrader groups in these environments.
Hybrid Cluster Proteins and Flavodiiron Proteins Afford Protection to Desulfovibrio vulgaris upon Macrophage Infection
Authors: Figueiredo Mafalda C. O. , Lobo Susana A. L. , Sousa Sara H. , Pereira Fábio P. , Wall Judy D. , Nobre Lígia S. , Saraiva Lígia M.
Published: April 2013

Desulfovibrio
species are Gram-negative anaerobic sulfate-reducing bacteria that colonize the human gut. Recently,
Desulfovibrio
spp. have been implicated in gastrointestinal diseases and shown to stimulate the epithelial immune response, leading to increased production of inflammatory cytokines by macrophages. Activated macrophages are key cells of the immune system that impose nitrosative stress during phagocytosis. Hence, we have analyzed the
in vitro
and
in vivo
responses of
Desulfovibrio vulgaris
Hildenborough to nitric oxide (NO) and the role of the hybrid cluster proteins (HCP1 and HCP2) and rubredoxin oxygen oxidoreductases (ROO1 and ROO2) in NO protection. Among the four genes,
hcp2
was the gene most highly induced by NO, and the
hcp2
transposon mutant exhibited the lowest viability under conditions of NO stress. Studies in murine macrophages revealed that
D. vulgaris
survives incubation with these phagocytes and triggers NO production at levels similar to those stimulated by the cytokine gamma interferon (IFN-γ). Furthermore,
D. vulgaris
hcp
and
roo
mutants exhibited reduced viability when incubated with macrophages, revealing that these gene products contribute to the survival of
D. vulgaris
during macrophage infection.
DNA Substrate-Induced Activation of the Agrobacterium VirB/VirD4 Type IV Secretion System
Authors: Cascales Eric , Atmakuri Krishnamohan , Sarkar Mayukh K. , Christie Peter J.
Published: April 2013

The bitopic membrane protein VirB10 of the
Agrobacterium
VirB/VirD4 type IV secretion system (T4SS) undergoes a structural transition in response to sensing of ATP binding or hydrolysis by the channel ATPases VirD4 and VirB11. This transition, detectable as a change in protease susceptibility, is required for DNA substrate passage through the translocation channel. Here, we present evidence that DNA substrate engagement with VirD4 and VirB11 also is required for activation of VirB10. Several DNA substrates (oncogenic T-DNA and plasmids RSF1010 and pCloDF13) induced the VirB10 conformational change, each by mechanisms requiring relaxase processing at cognate
oriT
sequences. VirD2 relaxase deleted of its translocation signal or any of the characterized relaxases produced in the absence of cognate DNA substrates did not induce the structural transition. Translocated effector proteins, e.g., VirE2, VirE3, and VirF, also did not induce the transition. By mutational analyses, we supplied evidence that the N-terminal periplasmic loop of VirD4, in addition to its catalytic site, is essential for early-stage DNA substrate transfer and the VirB10 conformational change. Further studies of VirB11 mutants established that three T4SS-mediated processes, DNA transfer, protein transfer, and pilus production, can be uncoupled and that the latter two processes proceed independently of the VirB10 conformational change. Our findings support a general model whereby DNA ligand binding with VirD4 and VirB11 stimulates ATP binding/hydrolysis, which in turn activates VirB10 through a structural transition. This transition confers an open-channel configuration enabling passage of the DNA substrate to the cell surface.
Nontypeable Haemophilus influenzae Carbonic Anhydrase Is Important for Environmental and Intracellular Survival
Authors: Langereis Jeroen D. , Zomer Aldert , Stunnenberg Hendrik G. , Burghout Peter , Hermans Peter W. M.
Published: April 2013

Nontypeable
Haemophilus influenzae
(NTHi) is one of the leading causes of noninvasive mucosal infections, such as otitis media, sinusitis, and conjunctivitis. During its life cycle, NTHi is exposed to different CO
2
levels, which vary from ∼0.04% in ambient air during transmission to a new host to over 5% in the respiratory tract and tissues of the human host during colonization and disease. We used the next-generation sequencing Tn-seq technology to identify genes essential for NTHi adaptation to changes in environmental CO
2
levels. It appeared that
H. influenzae
carbonic anhydrase (HICA), which catalyzes the reversible hydration of CO
2
to bicarbonate, is a molecular factor that is conditionally essential for NTHi survival in ambient air. Growth of NTHi Δ
can
strains was restored under 5% CO
2
-enriched conditions, by supplementation of the growth medium with sodium bicarbonate, or by genetic complementation with the
can
gene. Finally, we showed that HICA not only is essential for environmental survival but also appeared to be important for intracellular survival in host cells. Hence, HICA is important for NTHi niche adaptation.
Disseminated tuberculosis presenting with secondary haemophagocytic lymphohistiocytosis and Poncet's disease in an immunocompetent individual
Authors: Naha Kushal , Dasari Sowjanya , Vivek G , Prabhu Mukhyaprana
Published: April 2013

We report a 27-year-old previously healthy man, who presented with fever and painful swelling of both ankles for 6 months, and who had been jaundiced for 1 week. Clinical examination revealed diffuse macular rash, severe pallor, deep icterus, generalised lymphadenopathy and hepatosplenomegaly. Detailed evaluation revealed granulomata in bone marrow aspirate, and numerous acid fast bacilli in lymph node biopsy. Bone marrow PCR was also positive forMycobacterium tuberculosis. A diagnosis of disseminated tuberculosis was made and antitubercular therapy was initiated. Investigation also showed features of haemophagocytosis within the bone marrow. Results of further tests satisfied the criteria for haemophagocytic lymphohistiocytosis, probably secondary to tuberculosis. However, rapid deterioration in his clinical condition led to his death within 5 days of diagnosis, before appropriate therapy for haemophagocytic lymphohistiocytosis could be instituted. This case report highlights an unusual and deadly presentation of tuberculosis in an immunocompetent individual.
Titanium plate artefact mimicking popliteal artery dissection on digital subtraction CT angiography
Authors: Woodacre Timothy , Wienand-Barnett Sophie
Published: April 2013

Titanium plates used for the internal fixation of long bone fractures cause significant artefact on CT scans but have not been reported to affect digital subtraction CT angiography. We present a patient with clinical suspicion of popliteal artery injury following a high tibial osteotomy. The osteotomy was stabilised with a titanium locking plate. During the digital subtraction process used to produce reconstruction CT angiography, removal of artefact caused by the titanium plate produced CT images mimicking the appearance of a popliteal artery dissection. The imaging inaccuracy was realised prior to the patient undergoing further intervention. We highlight the potential error caused by titanium plates on digital subtraction CT angiography and recommend careful analysis of such images prior to further treatment.
Identification and Assessment of Anderson-Fabry Disease by Cardiovascular Magnetic Resonance Noncontrast Myocardial T1 Mapping
Authors: Sado Daniel M. , White Steven K. , Piechnik Stefan K. , Banypersad Sanjay M. , Treibel Thomas , Captur Gabriella , Fontana Marianna , Maestrini Viviana , Flett Andrew S. , Robson Matthew D. , Lachmann Robin H. , Murphy Elaine , Mehta Atul , Hughes Derralynn , Neubauer Stefan , Elliott Perry M. , Moon James C.
Published: April 2013

Background—

Anderson-Fabry disease (AFD) is a rare but underdiagnosed intracellular lipid disorder that can cause left ventricular hypertrophy (LVH). Lipid is known to shorten the magnetic resonance imaging parameter T1. We hypothesized that noncontrast T1 mapping by cardiovascular magnetic resonance would provide a novel and useful measure in this disease with potential to detect early cardiac involvement and distinguish AFD LVH from other causes.

Methods and Results—

Two hundred twenty-seven subjects were studied: patients with AFD (n=44; 55% with LVH), healthy volunteers (n=67; 0% with LVH), patients with hypertension (n=41; 24% with LVH), patients with hypertrophic cardiomyopathy (n=34; 100% with LVH), those with severe aortic stenosis (n=21; 81% with LVH), and patients with definite amyloid light-chain (AL) cardiac amyloidosis (n=20; 100% with LVH). T1 mapping was performed using the shortened modified Look-Locker inversion sequence on a 1.5-T magnet before gadolinium administration with primary results derived from the basal and midseptum. Compared with health volunteers, septal T1 was lower in AFD and higher in other diseases (AFD versus healthy volunteers versus other patients, 882±47, 968±32, 1018±74 milliseconds;
P
<0.0001). In patients with LVH (n=105), T1 discriminated completely between AFD and other diseases with no overlap. In AFD, T1 correlated inversely with wall thickness (
r
=−0.51;
P
=0.0004) and was abnormal in 40% of subjects who did not have LVH. Segmentally, AFD showed pseudonormalization or elevation of T1 in the left ventricular inferolateral wall, correlating with the presence or absence of late gadolinium enhancement (1001±82 versus 891±38 milliseconds;
P
<0.0001).

Conclusions—

Noncontrast T1 mapping shows potential as a unique and powerful measurement in the imaging assessment of LVH and AFD.
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis
Authors: Gray Stephen P. , Di Marco Elyse , Okabe Jun , Szyndralewiez Cedric , Heitz Freddy , Montezano Augusto C. , de Haan Judy B. , Koulis Christine , El-Osta Assam , Andrews Karen L. , Chin-Dusting Jaye P. F. , Touyz Rhian M. , Wingler Kirstin , Cooper Mark E. , Schmidt Harald H. H. W. , Jandeleit-Dahm Karin A
Published: April 2013

Background—

In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis.

Methods and Results—

Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specific Nox inhibitor, GKT137831, prevented oxidative stress in response to hyperglycemia in human aortic endothelial cells. To examine these observations in vivo, we investigated the role of Nox1 on plaque development in apolipoprotein E–deficient mice 10 weeks after induction of diabetes mellitus. Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation of chemokine expression, vascular adhesion of leukocytes, macrophage infiltration, and reduced expression of proinflammatory and profibrotic markers. Similarly, treatment of diabetic apolipoprotein E–deficient mice with GKT137831 attenuated atherosclerosis development.

Conclusions—

These studies identify a major pathological role for Nox1 and suggest that Nox1-dependent oxidative stress is a promising target for diabetic vasculopathies, including atherosclerosis.
Thucydides’ Take on the Corinthian Navy. οἵ τε γὰρ Κορίνθιοι ἡγήσαντο κρατεῖν εἰ µὴ καὶ πολὺ ἐκρατοῦντο, ‘The Corinthians believed they were victors if they were only just defeated’
Authors: McKenzie Nicholas J. , Hannah Patricia A.
Published: April 2013

Abstract

This paper closely examines Thucydides’ presentation of three naval battles fought in the Corinthian Gulf and the battle of Sybota off north-west Greece, in order to show how his version of the action does not just stress the pervasive impression of Athenian dominance and downplay the Peloponnesian performance, but extends to characterising the Corinthian fleet in a surprisingly negative way. In the first battle he claims that they were ignorant of the local weather patterns, in the second of the underwater hazards, and after the third that ‘The Corinthians believed they were victors if they were only just defeated’. His account of the earlier battle off Corcyra is similarly flawed, since by focussing on the participants’ treaty obligations he fails to bring out the significance of the Corinthian naval victory for the history of Greek warfare. The reader of The Peloponnesian War is encouraged not to question Thucydides’ disparaging record of the Corinthian navy, as it reinforces his focus on a bipartite contest between Athens and Sparta. However, a case is made here for a more positive assessment of Corinthian involvement in the modified design of the trireme and the revision of naval tactics in the late fifth century BC.
Enhancing the thermal comfort of fabrics for the footwear industry
Authors: Borreguero Ana Maria , Talavera Beatriz , Rodriguez Juan Francisco , Valverde Jose Luis , Gonzalez Jose Luis , Carmona Manuel
Published: April 2013

A nonwoven fabric, three foams and leather, commonly used as fabrics for shoe manufacturing, were doped with microcapsules containing phase change materials (PCMs) and also with carbon nanofibers (CNFs) in order to improve the thermal comfort provided by the shoes. The maximum microcapsule content that can be incorporated and the influence on the weight, thickness and the thermal properties and behavior of the fabrics were evaluated. The resulting materials showed a thermal energy storage (TES) capacity up to 13.74 J/g and a maximum thickness increase of the composite fabric of 0.6 mm. The PCMs addition promoted a slight modification of the steady-state temperatures of the fabrics subjected to heating or cooling processes and the stored and released heats confirmed that PCMs work in a reversible way. On the other hand, the addition of CNFs compensated for the insulating effect of the PCMs. Finally, it was found that footwear containing these materials could hold the foot temperature for a longer time than parent fabrics.
Transfemoral balloon expandable aortic valve implantation in a patient with myelodysplastic syndrome
Authors: Akçay M , Sarı C , Durmaz T , Keleş T , Özen MB , Bayram NA , Bilen E , Ayhan H , Kasapkara HA , Bozkurt E
Published: April 2013

In this case presentation, the transcatheter aortic valve implantation (TAVI) intervention successfully performed on a 76-year-old male patient with severe degenerative aortic stenosis and diagnosed with myelodysplastic syndrome (MDS) is discussed. This case presentation represents the first case on the treatment of severe aortic stenosis on a patient with myelodysplastic syndrome through the use of the TAVI method and may form an alternative to surgery in patients with severe aortic stenosis who have a known haematological disease. For a successful procedure, the patient must be evaluated in cooperation with the haematology clinic and all necessary precautions regarding bleeding and infection complications of the patient must be taken prior to the procedure.
Triptan nonresponders: Do they exist and who are they?
Authors: Viana Michele , Genazzani Armando A , Terrazzino Salvatore , Nappi Giuseppe , Goadsby Peter J
Published: April 2013

Background:

Triptans represent the best treatment option for most migraine attacks, although this is not as well studied as it might be in controlled trials. Their efficacy and tolerability vary, both between agents, and from patient to patient, with about 30%–40% of patients not responding adequately to therapy. As yet unexplained, the failure of one triptan does not predict failure with another, and therefore triptan nonresponders cannot be defined as individuals who have failed a single triptan. Five clinical studies provide evidence that switching from a triptan that is ineffective to a second one can result in effective treatment in a proportion of patients. Systematic studies investigating whether there are patients who do not respond to all triptans in all formulations are lacking.

Methods:

Here we discuss the importance of identifying triptan nonresponders, the literature supporting their existence, and the issues to be resolved to design trials to investigate this.

Conclusion:

So far, no scientific data about the presence of a triptan nonresponder population are available. We propose a pragmatic study design to assess the existence of this subpopulation, recognizing the complexity of the question and the likelihood that more than one issue is at play in nonresponders.
Dystrophinopathy Diagnosis Made Easy
Authors: Chakrabarty Biswaroop , Sharma M. C. , Gulati Sheffali , Kabra Madhulika , Pandey R. M. , Sarkar Chitra
Published: April 2013

Dystrophinopathies are diagnosed by genetic studies and muscle biopsy. Most centers have multiplex polymerase chain reaction facilities diagnosing 65% to 70% of dystrophinopathy cases. Muscle biopsy is a time-consuming, invasive procedure whereas skin biopsy is a simple procedure done under local anesthesia. The current study evaluated the diagnostic accuracy of skin biopsy in dystrophinopathy. Overall, 119 confirmed cases of muscular dystrophy (111 males and 8 females) were included in the final analysis, of which 100 (all males) were dystrophinopathy. Skin biopsy diagnosed dystrophinopathy in suspected muscular dystrophy patients with a sensitivity of 98% (92.3%-99.7%), specificity of 99% (93.7%-99.9%), positive predictive value of 94.7% (71.9%-99.7%), and negative predictive value of 90% (66.9%-98.2%). Skin biopsy can be used for screening dystrophinopathy in muscular dystrophy patients (high sensitivity and positive predictive value). It being a simple and minimally invasive procedure, histopathologic and molecular markers of disease progression and response to novel treatment options can be assessed serially.
Increasing the power of piezoelectric energy harvesters by magnetic stiffening
Authors: Al-Ashtari Waleed , Hunstig Matthias , Hemsel Tobias , Sextro Walter
Published: April 2013

A piezoelectric cantilever beam with a tip mass at its free end is a common energy harvester configuration. This article introduces a new principle of designing such a harvester that increases the generated power without changing the resonance frequency of the harvester: the attraction force between two permanent magnets is used to add stiffness to the system. This magnetic stiffening counters the effect of the tip mass on the efficient operation frequency. Five set-ups incorporating piezoelectric bimorph cantilevers of the same type in different mechanical configurations are compared theoretically and experimentally to investigate the feasibility of this principle: theoretical and experimental results show that magnetically stiffened harvesters have important advantages over conventional set-ups with and without tip mass. They generate more power while only slightly increasing the deflection in the piezoelectric harvester and they can be tuned across a wide range of excitation frequencies.
Robust loop-shaping control for a nano-positioning stage
Authors: Wang Fu-Cheng , Chen Lien-Sheng , Tsai Yan-Chen , Hsieh Chin-Hui , Yen Jia-Yush
Published: April 2013

This paper proposes robust loop-shaping techniques for a two-axis nano-positioning piezoelectric stage. Piezoelectric transducers are usually used to drive precision mechanisms because of their favorable properties, such as high resolution, high accuracy, and large driving force. However, the nonlinear characteristics of piezoelectric materials can degrade system performance. Therefore, we model a piezoelectric stage as a linear system, and regard its nonlinear factors as system uncertainties. Because robust control can guarantee stability and performance for systems with uncertainties and disturbances, we apply loop-shaping techniques and design standard robust controllers for the stage. In addition, we consider fixed-order robust control for the system in that controllers with lower orders are preferred for hardware implementation. Lastly, the designed controllers are implemented for experimental verification. The results demonstrate the effectiveness of these robust controllers in tracking reference signals and suppressing high-frequency vibrations.
Dynamic analysis of the train and slab track coupling system with finite elements in a moving frame of reference
Authors: Lei Xiaoyan , Wang Jian
Published: April 2013

Slab tracks are widely used worldwide in high-speed railways. In order to investigate the dynamic behavior of the train and slab track coupling system, a new approach, based on conceptions of the vehicle element and track element, is developed with finite elements in a moving frame of reference. By discretizing the slab track subsystem into track elements that flow with the moving vehicle, the proposed method eliminates the need for keeping track of the vehicle position with respect to the track model. The governing equations are formulated in a coordinate system traveling at a constant velocity, and the associated stiffness matrix, mass matrix and damping matrix for the track element in a moving frame of reference are derived. The vehicle element is introduced to model a car with primary and secondary suspension systems, which has 26 degrees of freedom, where 10 degrees of freedom are used to describe the vertical movement of the car, and 16 degrees of freedom are associated with the rail displacements. In the numerical study, four cases of application examples are presented taking into consideration the effects of track roughness, train speed and track parameters. The numerical solutions compare favorably with the results obtained by alternative methods. The method is shown to work for varying train speed and track parameters, and has several advantages over the conventional finite element method in a fixed system of reference.
Passive and adaptive vibration suppression of pipes conveying fluid with variable velocity
Authors: Yang Tian-Zhi , Yang Xiao-Dong , Li Yuhang , Fang Bo
Published: April 2013

A passive and adaptive control method for stabilizing a pipe conveying fluid is presented. Owing to fluid–pipe interactions, pipes are subjected to excessive vibrations. Classical passive control methods are only valid for stabilizing the pipes over a narrow range of flow velocities. In this paper, the theory of nonlinear targeted energy transfer (TET) is applied to suppress the excessive vibration of a pipe by using an essentially nonlinear attachment, which is called a nonlinear energy sink (NES). Numerical evidence for a passive TET between the pipe and NES is proposed. Results show that the NES can robustly absorb and dissipate a major portion of the vibrational energy of the pipe.
Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out
Authors: Miura Shin-ichiro , Matsuo Yoshino , Nakayama Asuka , Tomita Sayo , Suematsu Yasunori , Saku Keijiro
Published: April 2013

Introduction:

The recently approved angiotensin II (Ang II) type 1 (AT1) receptor blocker (ARB) azilsartan strongly reduces blood pressure (BP) in patients with hypertension. We previously reported that azilsartan showed unique binding behavior to the AT1 receptor because of its 5-oxo-1,2,4-oxadiazole moiety. However, the ability of azilsartan to block Ang II-dependent AT1 receptor activation is not yet clear.

Materials and methods:

Azilsartan and a derivative of azilsartan (azilsartan-7H) that lacks a carboxyl group at the benzimidazole ring were used. Ang II-induced inositol phosphate (IP) production and extracellular signal-regulated kinase (ERK) activation were analyzed in a cell-based wash-out assay.

Results:

Azilsartan, but not azilsartan-7H, completely blocked Ang II-induced IP production and ERK activation. Our previous report demonstrated that azilsartan mainly interacts with Tyr113, Lys199, and Gln257 in the AT1 receptor. The interactions between azilsartan and Tyr113 and Gln257, but not Lys199, were critical for blocking Ang II-induced IP production and ERK activation after wash-out.

Conclusions:

Although our findings regarding the molecule-specific effects of azilsartan are based on basic research, they may lead to an exciting insight into the mechanism of azilsartan.
Evaluating the Value for Money of Interventions to Support Behavior Change for Better Health (Behavior Change Evaluation Tools)
Authors: Lister Graham , Merritt Rowena
Published: April 2013

This article reports the development of tools for use by local commissioning teams, based in English Local Authorities (Local Government Councils), to evaluate the value for money of their behavior change investments. The national program was guided by a panel of senior advisers and included consultations with experts in the field, as the basis for the design of the methodology. Evaluation tools were then developed applying evidence provided by the National Institute for Health and Clinical Excellence, the World Health Organization, Health England (a national group set up to advise on public health policy), and other sources. As data were often incomplete, provision was made to update the tools as further evidence emerges. The tools, which are now available online at http://www.thensmc.com/resources/vfm , cover: smoking cessation, alcohol harm reduction, obesity reduction, comprising, weight loss, diet and increased activity, breast feeding continuation, and participation in bowel cancer screening. The use of these tools by local teams has proved valuable in demonstrating the relative value for money of local interventions and the importance of further developments of this kind.
National identity building through patterns of an international third-person perception in news coverage
Authors: Müller Philipp
Published: April 2013

This article argues that news coverage plays an important role for national identity building in the way that it evaluates the own nation better than foreign nations (in-group/out-group bias). This notion is being transferred to the media as an element of national cultural identity. This article identifies analogies between national identity building through the mass media and the third-person perception, which states that people assume others to be more vulnerable to negative media influences. It is hypothesized that patterns of an international third-person perception occur in news coverage, i.e. the news media should present media influences in the own country to be weaker than in other countries. A first standardized content analysis ( N = 2204) of newspaper coverage from the US and Germany on elections in own and other countries supports this hypothesis. Consequences are discussed and directions for future research are pointed out.
Prognostic impact and targeting of CRM1 in acute myeloid leukemia
Authors: Kojima Kensuke , Kornblau Steven M. , Ruvolo Vivian , Dilip Archana , Duvvuri Seshagiri , Davis R. Eric , Zhang Min , Wang Zhiqiang , Coombes Kevin R. , Zhang Nianxiang , Qiu Yi Hua , Burks Jared K. , Kantarjian Hagop , Shacham Sharon , Kauffman Michael , Andreeff Michael
Published: April 2013

Key Points

High CRM1 expression was associated with short survival of AML patients. CRM1 inhibitor KPT-185 induces apoptosis mainly in a p53-dependent manner, whereas inhibition of proliferation was p53 independent.
CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age
Authors: Gekas Christos , Graf Thomas
Published: April 2013

Key Points

Integrin CD41, thought to absent on adult HSCs, marks a novel subset of myeloid-biased long-term HSCs that becomes prevalent with age. Loss of CD41 leads to transplantable hematopoietic defects that affect HSC survival and maintenance and are, in part, mediated by platelet loss.
Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis
Authors: Maldonado Fabien , Moua Teng , Rajagopalan Srinivasan , Karwoski Ronald A. , Raghunath Sushravya , Decker Paul A. , Hartman Thomas E. , Bartholmai Brian J. , Robb Richard A. , Ryu Jay H.
Published: April 2013

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival.

We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists’ assessments and clinical outcomes.

Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality.

These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis.
Rhinovirus infection and healthcare utilisation in prematurely born infants
Authors: Drysdale Simon B. , Alcazar-Paris Mireia , Wilson Theresa , Smith Melvyn , Zuckerman Mark , Broughton Simon , Rafferty Gerrard F. , Peacock Janet L. , Johnston Sebastian L. , Greenough Anne
Published: April 2013

Our aim was to determine whether rhinovirus (RV) lower respiratory tract infections (LRTIs) in prematurely born infants increase health-related cost of care during infancy.

153 infants born at <36 weeks of gestation were prospectively followed to 1 year. Cost of care was calculated from the National Health Service reference costing scheme and healthcare utilisation determined by examining hospital/general practitioner records.

20 infants developed RV LRTIs (RV group), 17 respiratory syncytial virus (RSV) LRTIs (RSV group), 12 both RV and RSV LRTIs (RV/RSV group) and 74 had no LRTI (no LRTI group). Compared with the no LRTI group, the RV/RSV LRTI group had the greatest increase in adjusted mean cost (difference GBP 5769), followed by the RV LRTI group (difference GBP 278) and, finally, the RSV LRTI group (difference GBP 172) (p=0.045). The RV group had more outpatient (p<0.05) and respiratory-related general practitioner (p<0.05) attendances, more wheezed at follow-up (p<0.001) than the no LRTI group and more had respiratory-related outpatient attendances than the RSV LRTI group (p<0.05).

We conclude that RV LRTIs were associated with increased health-related cost of care during infancy; our results suggest that the RV group compared with the RSV group suffered greater chronic respiratory morbidity.