bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Regular Exercise Among Iranian Adults: A Study in Northern Iran
Authors: Maddah Mohsen , Akbarian Zahra , Shoyooie Solmaz , Rostamnejad Maryam , Soleimani Mehdi
Published: July 2014

Background:

Regular exercise is an important aspect of physical activity for people living in urban areas. We examined prevalence of regular exercise in leisure times and some related factors in middle aged men and women in northern Iran.

Method:

A cross-sectional survey was undertaken on 1425 women and 676 men in 2 main cities in northern Iran. Information on exercise habits was collected using a self-administrated questionnaire. Regular exercise was defined as any kind of recreational or sport physical activity other than walking performed three or more days per week for at least 20 minutes. Questions on perceived barriers on regular exercise and walking habit were also included in the questionnaire.

Results:

Findings showed that 11.2% of the participants (9% in women and 12.8% in men P < .05) did exercise regularly. Prevalence of doing regular exercise was inversely related to age in women but not in men. Educated women were more likely to do regular exercise. The most common perceived barrier for regular exercise was time insufficiency.

Conclusion:

Only a small proportion of the study men and women had sustainable regular exercise for 1 year. Regular exercise was more common among young and well educated women than older women and the men.
Predictors of Children’s Active Commuting to School: An Observational Evaluation in 5 U.S. Communities
Authors: Mendoza Jason A. , Cowan David , Liu Yan
Published: July 2014

Background:

Few reports examined long term predictors of children’s active commuting to school (walking or cycling to school, ACS).

Purpose:

To identify predictors of ACS over 1 school year among a sample of children with relatively high rates of ACS.

Methods:

Parents were surveyed in September 2010 (Time 1) and April 2011 (Time 2). The dependent variable was children’s commuting mode to school (active versus passive). Independent variables included: 1) parents’ outcome expectations (from Social Cognitive Theory: the expected risks/benefits for their child doing ACS), 2) distance to school, 3) participation in an adult-led walk to school group, 4) temperature, and 5) child demographics. Generalized mixed-models estimated odds ratios for ACS (n = 369 or 49.7% of Time 1 respondents).

Results:

Males (OR = 2.59, 95% CI [1.57–4.30]), adult-led walk to school group participation (OR = 1.80, 95% CI [1.14–2.86]), parents’ outcome expectations (OR = 1.26, 95% CI [1.14–1.39]), temperature (OR = 1.03, 95% CI [1.01–1.07), distance to school (OR = 0.23, 95% CI [0.14–0.37]), and Latino ethnicity (OR = 0.28, 95% CI [0.12–0.65]) were associated with ACS.

Conclusions:

Programs and policies sensitive to parents’ concerns (eg, adult-led walk to school groups) and targeting Latinos and girls appear promising for increasing ACS.
Shifting and Narrowing Masculinity Hierarchies in Physical Education: Status Matters
Authors: Tischler Amy , McCaughtry Nate
Published: July 2014

The purpose of this study was to examine boys’ perceptions of masculinity hierarchies in adventure physical education in relation to past experiences in sport-based physical education and their evolving views about physical activity in their lives. Theoretical principles of masculinity guided this study. Data were collected with 55 male high school students through 84 formal interviews, 200 e-mail interviews, and 135 ninety-minute class observations over 15 weeks. Data were analyzed using constant comparison with frequent member checks to facilitate trustworthiness. Three main findings emerged. First, boys described masculinity hierarchies in many past sport-based physical education classes as static and well-pronounced, which for many negatively impacted their perceptions of and engagement with physical activity. Second, boys described masculinity hierarchies in adventure physical education at Apex High School as shifting and narrowing, which stood in stark contrast to the inequitable status differentials in many sport-based physical education classes. Third, shifting and narrowing masculinity hierarchies resulted in significant positive outcomes for boys, most notably enhancing their orientations toward physical activity. Findings from this study suggest that physical education settings that produce shifting and narrowing masculinity hierarchies can enhance boys’ perceptions of and engagement with physical activity both in and out of school.
Understanding Differences in Role Stressors, Resilience, and Burnout in Teacher/Coaches and Non-Coaching Teachers
Authors: Richards K. Andrew R. , Templin Thomas J. , Levesque-Bristol Chantal , Blankenship Bonnie Tjeerdsma
Published: July 2014

The constructs of role stressors, burnout, and resilience have been the topic of numerous research studies in physical education and education more generally. Specific to physical education, much effort has been devoted to the study of teacher/coach role conflict. However, no prior studies have examined how role stressors, burnout, and resilience experienced by teacher/coaches differ from what is experienced by noncoaching teachers. Using role theory as a guiding framework, this study sought to examine differences in role stressors, burnout, and resilience among teacher/coaches and noncoaching teachers from core (e.g., mathematics, language arts) and noncore (e.g., physical education, music) subjects. Analyses were conducted using 2 × 2 (coaching status × subject affiliation) Factorial ANOVAs. While some group differences are highlighted, overall the results suggest that there are more similarities than differences among teacher/coaches and noncoaching teachers. These findings suggest that it is not safe to assume that dual role teacher/coaches will always experience more role stress and burnout than noncoaching teachers. Additional research is needed to more fully understand the implications of being a dual role teacher/coach.
Global manufacturing and the future of technology
Authors: Fuchs Erica R. H.
Published: July 2014

Where you manufacture changes what you get
Response to Comment on “Mechanism of eukaryotic RNA polymerase III transcription termination”
Authors: Nielsen Soren , Zenkin Nikolay
Published: July 2014

Arimbasseri
et al
., in their Comment, suggest that to terminate transcription in vivo, RNA polymerase III uses a mechanism other than hairpin-dependent termination and that properties of purified polymerase may depend on preparation procedure. Evidence suggests that our preparation is indeed different from that of other methods. Our new data suggest that, apart from hairpin-dependent termination, one or more “fail-safe” termination mechanisms may exist in the cell.
An epigenetic window into the past?
Authors: Orlando Ludovic , Willerslev Eske
Published: July 2014

DNA damage in ancient genomes may provide insight into past regulatory changes in humans and other species
A gem of a quantum teleporter
Authors: Atatüre Mete , Morton John J. L.
Published: July 2014

Diamond-based quantum teleportation works every time

[Also see Research Article by

Pfaff
et al.

]
Key narcolepsy–influenza vaccine findings retracted
Authors: Underwood Emily
Published: July 2014

Stanford researchers unable to replicate findings linking immune response to sleep disorder.
A nontumorigenic variant of FGF19 treats cholestatic liver diseases
Authors: Luo Jian , Ko Brian , Elliott Michael , Zhou Mei , Lindhout Darrin A. , Phung Van , To Carmen , Learned R. Marc , Tian Hui , DePaoli Alex M. , Ling Lei
Published: July 2014

Nontumorigenic FGF19 variants represent an effective approach for the prevention and treatment of cholestatic liver diseases.
Partial Activation of Natural Killer and γδ T Cells by Classical Swine Fever Viruses Is Associated with Type I Interferon Elicited from Plasmacytoid Dendritic Cells
Authors: Franzoni Giulia , Edwards Jane C. , Kurkure Nitin V. , Edgar Daniel S. , Sanchez-Cordon Pedro J. , Haines Felicity J. , Salguero Francisco J. , Everett Helen E. , Bodman-Smith Kikki B. , Crooke Helen R. , Graham Simon P.
Published: July 2014

Vaccination with live attenuated classical swine fever virus (CSFV) vaccines can rapidly confer protection in the absence of neutralizing antibodies. With an aim of providing information on the cellular mechanisms that may mediate this protection, we explored the interaction of porcine natural killer (NK) cells and γδ T cells with CSFV. Both NK and γδ T cells were refractory to infection with attenuated or virulent CSFV, and no stimulatory effects, as assessed by the expression of major histocompatibility complex (MHC) class II (MHC-II), perforin, and gamma interferon (IFN-γ), were observed when the cells were cultured in the presence of CSFV. Coculture with CSFV and myeloid dendritic cells (mDCs) or plasmacytoid dendritic cells (pDCs) showed that pDCs led to a partial activation of both NK and γδ T cells, with upregulation of MHC-II being observed. An analysis of cytokine expression by infected DC subsets suggested that this effect was due to IFN-α secreted by infected pDCs. These results were supported by
ex vivo
analyses of NK and γδ T cells in the tonsils and retropharyngeal lymph nodes from pigs that had been vaccinated with live attenuated CSFV and/or virulent CSFV. At 5 days postchallenge, there was evidence of significant upregulation of MHC-II but not perforin on NK and γδ T cells, which was observed only following a challenge of the unvaccinated pigs and correlated with increased CSFV replication and IFN-α expression in both the tonsils and serum. Together, these data suggest that it is unlikely that NK or γδ T cells contribute to the cellular effector mechanisms induced by live attenuated CSFV.
Multi-Virulence-Locus Sequence Typing of Staphylococcus lugdunensis Generates Results Consistent with a Clonal Population Structure and Is Reliable for Epidemiological Typing
Authors: Didi Jennifer , Lemée Ludovic , Gibert Laure , Pons Jean-Louis , Pestel-Caron Martine
Published: July 2014

Staphylococcus lugdunensis
is an emergent virulent coagulase-negative staphylococcus responsible for severe infections similar to those caused by
Staphylococcus aureus
. To understand its potentially pathogenic capacity and have further detailed knowledge of the molecular traits of this organism, 93 isolates from various geographic origins were analyzed by multi-virulence-locus sequence typing (MVLST), targeting seven known or putative virulence-associated loci (

atlL
R2

,

atlL
R3

,
hlb
,
isdJ
, SLUG_09050, SLUG_16930, and
vwbl
). The polymorphisms of the putative virulence-associated loci were moderate and comparable to those of the housekeeping genes analyzed by multilocus sequence typing (MLST). However, the MVLST scheme generated 43 virulence types (VTs) compared to 20 sequence types (STs) based on MLST, indicating that MVLST was significantly more discriminating (Simpson's index [
D
], 0.943). No hypervirulent lineage or cluster specific to carriage strains was defined. The results of multilocus sequence analysis of known and putative virulence-associated loci are consistent with a clonal population structure for
S. lugdunensis
, suggesting a coevolution of these genes with housekeeping genes. Indeed, the nonsynonymous to synonymous evolutionary substitutions (

d
N

/

d
S

) ratio, the Tajima's D test, and Single-likelihood ancestor counting (SLAC) analysis suggest that all virulence-associated loci were under negative selection, even

atlL
R2

(AtlL protein) and SLUG_16930 (FbpA homologue), for which the

d
N

/

d
S

ratios were higher. In addition, this analysis of virulence-associated loci allowed us to propose a trilocus sequence typing scheme based on the intragenic regions of

atlL
R3

,
isdJ
, and SLUG_16930, which is more discriminant than MLST for studying short-term epidemiology and further characterizing the lineages of the rare but highly pathogenic
S. lugdunensis
.
Commutability of the Epstein-Barr Virus WHO International Standard across Two Quantitative PCR Methods
Authors: Abeynayake Janaki , Johnson Ryan , Libiran Paolo , Sahoo Malaya K. , Cao Hongbin , Bowen Raffick , Chan K. C. Allen , Le Quynh-Thu , Pinsky Benjamin A.
Published: July 2014

The commutability of international reference standards is critical for ensuring quantitative agreement across different viral load assays. Here, we demonstrate the commutability of the Epstein-Barr virus (EBV) WHO international standard for the BamHI-W and artus EBV assays.
Clinical Validation of the Lyra Direct HSV 1+2/VZV Assay for Simultaneous Detection and Differentiation of Three Herpesviruses in Cutaneous and Mucocutaneous Lesions
Authors: Fan Feinan , Stiles Jeffrey , Mikhlina Albina , Lu Xuedong , Babady N. Esther , Tang Yi-Wei
Published: July 2014

We evaluated the Lyra Direct HSV 1+2/VZV multiplex real-time PCR assay for the detection and differentiation of herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) on 695 consecutive cutaneous and mucocutaneous lesion specimens. The intra-assay and interassay coefficient of variation values for the Lyra assay were 0.29 to 1.30% and 2.33 to 2.61%, respectively. The sensitivities, specificities, and positive and negative predictive values were 93.4 to 95.0%, 96.1 to 96.8%, 78.0 to 80.3%, and 99.0 to 99.1%, respectively, in comparison to those of viral culture. The values were further improved when a resolution analysis was performed with a laboratory-developed PCR assay.
Combined Effects of the Structural Heterogeneity and Dynamics of Flaviviruses on Antibody Recognition
Authors: Dowd Kimberly A. , Mukherjee Swati , Kuhn Richard J. , Pierson Theodore C.
Published: July 2014

Flaviviruses are thought to sample an ensemble of structures at equilibrium. One consequence of a structurally dynamic virion is the observed time-dependent increases in neutralization sensitivity that can occur after prolonged incubation with antibody. Differences in how virus strains “breathe” may affect epitope exposure and contribute to the underlying mechanisms of strain-dependent neutralization sensitivity. Beyond the contribution of structural dynamics, flaviviruses exist as a structurally heterogeneous population due to an inefficient virion maturation process. Here, we investigate the interplay between virion maturation and structural dynamics that contributes to antibody-mediated neutralization. Using West Nile (WNV) and dengue (DENV) viruses produced under conditions that modify the extent of virion maturation, we investigated time-dependent changes in neutralization sensitivity associated with structural dynamics. Our results identify distinct patterns of neutralization against viruses that vary markedly with respect to the extent of virion maturation. Reducing the efficiency of virion maturation resulted in greater time-dependent changes in neutralization potency and a marked reduction in the stability of the particle at 37°C compared to more mature virus. The fact that the neutralization sensitivity of WNV and DENV did not increase after prolonged incubation in the absence of antibody, regardless of virion maturation, suggests that the dynamic processes that govern epitope accessibility on infectious viruses are reversible. Against the backdrop of heterogeneous flavivirus structures, differences in the pathways by which viruses “breathe” represent an additional layer of complexity in understanding maturation state-dependent patterns of antibody recognition.

IMPORTANCE
Flaviviruses exist as a group of related structures at equilibrium that arise from the dynamic motion of E proteins that comprise the antigenic surface of the mature virion. This process has been characterized for numerous viruses and is referred to as viral “breathing.” Additionally, flaviviruses are structurally heterogeneous due to an inefficient maturation process responsible for cleaving prM on the virion surface. Both of these mechanisms vary the exposure of antigenic sites available for antibody binding and impact the ability of antibodies to neutralize infection. We demonstrate that virions with inefficient prM cleavage “breathe” differently than their more mature counterparts, resulting in distinct patterns of neutralization sensitivity. Additionally, the maturation state was found to impact virus stability in solution. Our findings provide insight into the complex flavivirus structures that contribute to infection with the potential to impact antibody recognition.
Herpes Simplex Virus 1 Counteracts Viperin via Its Virion Host Shutoff Protein UL41
Authors: Shen Guanghui , Wang Kezhen , Wang Shuai , Cai Mingsheng , Li Mei-li , Zheng Chunfu
Published: July 2014

The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.
Reemergence of Chikungunya Virus
Authors: Morrison Thomas E.
Published: July 2014

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes acute fever and acute and chronic musculoskeletal pain in humans. Since 2004, CHIKV has caused millions of cases of disease in the Indian Ocean region and has emerged in new areas, including Europe, the Middle East, and the Pacific region. The mosquito vectors for this virus are globally distributed in tropical and temperate zones, providing the opportunity for CHIKV to continue to expand into new geographic regions. In October 2013, locally acquired cases of CHIKV infection were identified on the Caribbean island of Saint Martin, signaling the arrival of the virus in the Western Hemisphere. In just 9 months, CHIKV has spread to 22 countries in the Caribbean and Central and South America, resulting in hundreds of thousands of cases. CHIKV disease can be highly debilitating, and large epidemics have severe economic consequences. Thus, there is an urgent need for continued research into the epidemiology, pathogenesis, prevention, and treatment of these infections.
A Single Amino Acid Substitution in the Novel H7N9 Influenza A Virus NS1 Protein Increases CPSF30 Binding and Virulence
Authors: Ayllon Juan , Domingues Patricia , Rajsbaum Ricardo , Miorin Lisa , Schmolke Mirco , Hale Benjamin G. , García-Sastre Adolfo
Published: July 2014

Although an effective interferon antagonist in human and avian cells, the novel H7N9 influenza virus NS1 protein is defective at inhibiting CPSF30. An I106M substitution in H7N9 NS1 can restore CPSF30 binding together with the ability to block host gene expression. Furthermore, a recombinant virus expressing H7N9 NS1-I106M replicates to higher titers
in vivo
, and is subtly more virulent, than the parental virus. Natural polymorphisms in H7N9 NS1 that enhance CPSF30 binding may be cause for concern.
Immunodominant CD4+T-Cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein
Authors: Chen Li , Zanker Damien , Xiao Kun , Wu Chao , Zou Quanming , Chen Weisan
Published: July 2014

Antigen-specific CD4+T cells are essential for effective virus-specific host responses, with recent human challenge studies (in volunteers) establishing their importance for influenza A virus (IAV)-specific immunity. However, while many IAV CD4+T cell epitopes have been identified, few are known to stimulate immunodominant CD4+T cell responses. Moreover, much remains unclear concerning the major antigen(s) responded to by the human CD4+T cells and the extents and magnitudes of these responses. We initiated a systematic screen of immunodominant CD4+T cell responses to IAV in healthy individuals. Usingin vitroexpanded-multispecificity IAV-specific T cell lines and individual IAV protein antigens produced by recombinant vaccinia viruses, we found that the internal matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of CD4+T cell responses. Ten epitopes derived from M1 and NP were definitively characterized. Furthermore, epitope sequence conservation analysis established that immunodominance correlated with an increased frequency of mutations, reflecting the fact that these prominent epitopes are under greater selective pressure. Such evidence that particular CD4+T cells are important for protection/recovery is of value for the development of novel IAV vaccines and for our understanding of different profiles of susceptibility to these major pathogens.

IMPORTANCEInfluenza virus causes half a million deaths annually. CD4+T cell responses have been shown to be important for protection against influenza and for recovery. CD4+T cell responses are also critical for efficient CD8+T cell response and antibody response. As immunodominant T cells generally play a more important role, characterizing these immunodominant responses is critical for influenza vaccine development. We show here that the internal matrix protein 1 (M1) and nucleoprotein (NP), rather than the surface proteins reported previously, are the immunodominant targets of CD4+T cell responses. Interestingly, these immunodominant epitope regions accumulated many mutations over time, which likely indicates increased immune pressure. These findings have significant implications for the design of T cell-based influenza vaccines.
Classic Nuclear Localization Signals and a Novel Nuclear Localization Motif Are Required for Nuclear Transport of Porcine Parvovirus Capsid Proteins
Authors: Boisvert Maude , Bouchard-Lévesque Véronique , Fernandes Sandra , Tijssen Peter
Published: July 2014

Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses.

IMPORTANCE
Most DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid protein (VP1) of porcine parvovirus. The major protein (VP2) nuclear localization was shown to depend on a complex structural motif. This motif can be used as a strategy by the virus to avoid transport of incorrectly folded proteins and to selectively import assembled trimers into the nucleus. Structural nuclear localization motifs can also be important for nuclear proteins without a classic basic amino acid stretch, including multimeric cellular proteins.
Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study
Authors: Hafström Ingiäld , Engvall Inga-Lill , Rönnelid Johan , Boonen Annelies , van der Heijde Désirée , Svensson Björn ,   on behalf of the BARFOT study group
Published: July 2014

Objective

To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change).

Design

Prospective, randomised study of patients with early RA.

Setting

Secondary level of care; six participating centres from southern Sweden; both urban and rural populations.

Participants

In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80 years of age and had a disease duration of less than 1 year.

Intervention

The patients were randomised to 7.5 mg prednisolone daily for 2 years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2 years.

Results

The frequency of patients with radiographic progression after 2 years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively.

Conclusions

The presence of RF and anti-CCP predicted radiographic progression in patients not treated with prednisolone but failed to predict progression in patients treated with this drug. The data suggest that early treatment with prednisolone may modulate not only inflammation but also autoimmunity-associated pathogenetic mechanisms.

Trial registration number

ISRCTN20612367.
Applying measures of discriminatory accuracy to revisit traditional risk factors for being small for gestational age in Sweden: a national cross-sectional study
Authors: Juárez Sol Pía , Wagner Phillip , Merlo Juan
Published: July 2014

Objectives

Small for gestational age (SGA) is considered as an indicator of intrauterine growth restriction, and multiple maternal and newborn characteristics have been identified as risk factors for SGA. This knowledge is mainly based on measures of average association (ie, OR) that quantify differences in average risk between exposed and unexposed groups. Nevertheless, average associations do not assess the discriminatory accuracy of the risk factors (ie, its ability to discriminate the babies who will develop SGA from those that will not). Therefore, applying measures of discriminatory accuracy rather than measures of association only, our study revisits known risk factors of SGA and discusses their role from a public health perspective.

Design

Cross-sectional study. We measured maternal (ie, smoking, hypertension, age, marital status, education) and delivery (ie, sex, gestational age, birth order) characteristics and performed logistic regression models to estimate both ORs and measures of discriminatory accuracy, like the area under the receiver operating characteristic curve (AU-ROC) and the net reclassification improvement.

Setting

Data were obtained from the Swedish Medical Birth Registry.

Participants

Our sample included 731 989 babies born during 1987–1993.

Results

We replicated the expected associations. For instance, smoking (OR=2.57), having had a previous SGA baby (OR=5.48) and hypertension (OR=4.02) were strongly associated with SGA. However, they show a very small discriminatory accuracy (AU-ROC≈0.5). The discriminatory accuracy increased, but remained unsatisfactorily low (AU-ROC=0.6), when including all variables studied in the same model.

Conclusions

Traditional risk factors for SGA alone or in combination have a low accuracy for discriminating babies with SGA from those without SGA. A proper understanding of these findings is of fundamental relevance to address future research and to design policymaking recommendations in a more informed way.
Admission via the emergency department in relation to mortality of adults hospitalised with community-acquired pneumonia: an analysis of the British Thoracic Society national community-acquired pneumonia audit
Authors: Rodrigo Chamira , Mckeever Tricia M , Woodhead Mark , Welham Sally , Lim Wei Shen
Published: July 2014

Objective

To determine the association between 30-day inpatient mortality and route of admission to hospital, for adults with community acquired pneumonia (CAP).

Methods

We studied 16 313 adults included in the British Thoracic Society (BTS) national CAP audit dataset. Comparisons were made between adults admitted via emergency departments (ED) with non-ED routes of admission, with regard to 30-day inpatient mortality. Secondary outcome measures were adherence to national CAP guidelines (time to first chest X-ray ≤4 h from admission; time to first antibiotic dose ≤4 h from admission; antibiotic choice; and antibiotic route of administration) by route of admission.

Results

Of adults hospitalised with CAP, 75.6% were admitted via ED; these adults had a greater prevalence of comorbid illness and higher disease severity in comparison with non-ED admissions. Adjusted 30-day inpatient mortality was similar for ED versus non-ED route of admission (OR 1.10, 95% CI 0.96 to 1.25). Admissions via ED were associated with faster processes of care (time to chest X-ray ≤4 h, adjusted OR 3.39, 95% CI 2.79 to 4.12; time to first antibiotic ≤4 h, adjusted OR 1.62, 95% CI 1.42 to 1.84) and greater use of intravenous antibiotics regardless of disease severity (adjusted OR 1.58, 95% CI 1.43 to 1.74).

Conclusions

Adults with CAP admitted via EDs have more comorbid illness and greater disease severity compared to those admitted via non-ED routes. Following adjustment for these differences, 30-day inpatient mortality was not associated with route of admission.
Optimal capacity and buffer size estimation under generalized Markov Fluids models and QoS parameters
Authors: Bavio José , Marrón Beatriz
Published: July 2014

Quality of service (QoS) for internet traffic management requires good traffic models and good estimation of sharing network resource. A link of a network processes all traffic and it is designed with certain capacity C and buffer size B. A Generalized Markov Fluid model (GMFM), introduced by Marrón (2012), is assumed for the sources because it describes in a versatile way the traffic, allows estimation based on traffic traces, and also consistent effective bandwidth (EB) estimation can be done. QoS, interpreted as buffer overflow probability, can be estimated for GMFM through the EB estimation and solving the optimization problem presented in Courcoubetis and Siris [ Perform. Eval. 48:5–23, 2002], the so-called inf-sup formulas. In this work, we implement a code to solve the inf-sup problem and other optimization related with it, that allow us to do traffic engineering in links of data networks to calculate both, minimum capacity required when QoS and buffer size are given or minimum buffer size required when QoS and capacity are given.
TAILORING FERROMAGNET–MOLECULE INTERFACES: TOWARDS MOLECULAR SPINTRONICS
Authors: RAMAN KARTHIK V. , ATODIRESEI NICOLAE , MOODERA JAGADEESH S.
Published: July 2014

Understanding the interaction of organic molecules adsorbed on magnetic surfaces has shown considerable progress in recent years. The creation of hybridized interface between carbon-based aromatic molecule and the magnetic surface is observed to give rise to new interface states with unique electronic and magnetic character. This study has opened up a molecular-design initiative to tailor the spin dependent electronic and magnetic functionalities of the hybrid interface. The purpose of this article is to provide a fundamental understanding of the spin-chemistry and spin-physics associated with the formation of such ferromagnet-molecule hybrid interfaces. We also discuss the recent progress in this field using state-of-the-art experiments and theoretical calculations with focus on the magnetic properties of the molecule and the magnetic surface. The study reveals several interesting interface phenomena: formation of induced molecular moment and exchange coupling with the magnetic surface, and molecular spin-filters. It also demonstrates significant changes in the magnetic anisotropy and inter-atomic magnetic exchange coupling of the magnetic surface. These studies open the possibilities of exploring new molecular functionalities toward further research in the subfield of interface-assisted molecular spintronics.
Inhibitors of the 5-lipoxygenase pathway activate pannexin1 channels in macrophages via the thromboxane receptor
Authors: da Silva-Souza Hercules A. , de Lira Maria Nathália , Patel Naman K. , Spray David C. , Persechini Pedro Muanis , Scemes Eliana
Published: July 2014

A multitude of environmental signaling molecules influence monocyte and macrophage innate and adaptive immune responses, including ATP and prostanoids. Interestingly, purinergic (P2) and eicosanoid receptor signaling interact such that the activation of P2 receptors leads to prostanoid production, which can then interfere with P2Y-mediated macrophage migration. Recent studies suggest that blockade of 5-lipoxygenase (5-LOX) in macrophages can activate a permeation pathway involved in the influx of dye and the release of ATP. Here, we provide evidence that pannexin1 (Panx1) is a component of this pathway and present the intracellular signaling molecules linking the thromboxane (TP) receptor to Panx1-mediated dye influx and ATP release. Using pharmacological tools and transgenic mice deficient in Panx1, we show that two 5-LOX pathway inhibitors induce ATP release and influx of dye in a Panx1-dependent manner. Electrophysiological recordings performed in wild-type and Panx1-deficient macrophages confirmed that these 5-LOX pathway inhibitors activate currents characteristic of Panx1 channels. We found that the mechanism by which Panx1 channels are activated under this condition involves activation of the TP receptor that is mediated by the cAMP/PKA pathway. This is to our knowledge the first evidence for the involvement of Panx1 in the TP receptor signaling pathway. Future studies aimed to clarify the contribution of this TP-Panx1 signaling network to macrophage immune responses are likely to be important for targeting inflammatory and autoimmune diseases.
CRTC2 activation in the suprachiasmatic nucleus, but not paraventricular nucleus, varies in a diurnal fashion and increases with nighttime light exposure
Authors: Highland Julie A. , Weiser Michael J. , Hinds Laura R. , Spencer Robert L.
Published: July 2014

Entrainment of the intrinsic suprachiasmatic nucleus (SCN) molecular clock to the light-dark cycle depends on photic-driven intracellular signal transduction responses of SCN neurons that converge on cAMP response element-binding protein (CREB)-mediated regulation of gene transcription. Characterization of the CREB coactivator proteins CREB-regulated transcriptional coactivators (CRTCs) has revealed a greater degree of differential activity-dependent modulation of CREB transactivational function than previously appreciated. In confirmation of recent reports, we found an enrichment of crtc2 mRNA and prominent CRTC2 protein expression within the SCN of adult male rats. With use of a hypothalamic organotypic culture preparation for initial CRTC2-reactive antibody characterization, we found that CRTC2 immunoreactivity in hypothalamic neurons shifted from a predominantly cytoplasmic profile under basal culture conditions to a primarily nuclear localization (CRTC2 activation) 30 min after adenylate cyclase stimulation. In adult rat SCN, we found a diurnal variation in CRTC2 activation (peak at zeitgeber time of 4 h and trough at zeitgeber time of 16–20 h) but no variation in the total number of CRTC2-immunoreactive cells. There was no diurnal variation of CRTC2 activation in the hypothalamic paraventricular nucleus, another site of enriched CRTC2 expression. Exposure of rats to light (50 lux) for 30 min during the second half of their dark (nighttime) phase produced CRTC2 activation. We observed in the SCN a parallel change in the expression of a CREB-regulated gene (FOS). In contrast, nighttime light exposure had no effect on CRTC2 activation or FOS expression in the paraventricular nucleus, nor did it affect corticosterone hormone levels. These results suggest that CRTC2 participates in CREB-dependent photic entrainment of SCN function.
Do movement-related beta oscillations change after stroke?
Authors: Rossiter Holly E. , Boudrias Marie-Hélène , Ward Nick S.
Published: July 2014

Stroke is the most common cause of physical disability in the world today. While the key element of rehabilitative therapy is training, there is currently much interest in approaches that “prime” the primary motor cortex to be more excitable, thereby increasing the likelihood of experience-dependent plasticity. Cortical oscillations reflect the balance of excitation and inhibition, itself a key determinant of the potential for experience-dependent plasticity. In the motor system, beta-band oscillations are important and are thought to maintain the resting sensorimotor state. Here we examined motor cortex beta oscillations during rest and unimanual movement in a group of stroke patients and healthy control subjects, using magnetoencephalography. Movement-related beta desynchronization (MRBD) in contralateral primary motor cortex was found to be significantly reduced in patients compared with control subjects. Within the patient group, smaller MRBD was seen in those with more motor impairment. We speculate that impaired modulation of beta oscillations during affected hand grip is detrimental to motor control, highlighting this as a potential therapeutic target in neurorehabilitation.
Overactivation of the supplementary motor area in chronic stroke patients
Authors: Amengual Julià L. , Münte Thomas F. , Marco-Pallarés Josep , Rojo Nuria , Grau-Sánchez Jennifer , Rubio Francisco , Duarte Esther , Grau Carles , Rodríguez-Fornells Antoni
Published: July 2014

Stroke induces a loss of neural function, but it triggers a complex amount of mechanisms to compensate the associated functional impairment. The present study aims to increase our understanding of the functional reshape of the motor system observed in chronic stroke patients during the preparation and the execution of movements. A cohort of 14 chronic stroke patients with a mild-to-moderate hemiparesis and 14 matched healthy controls were included in this study. Participants were asked to perform a bimanual reaction time task synchronizing alternated responses to the presentation of a visual cue. We used Laplacian-transformed EEG activity (LT-EEG) recorded at the locations Cz and C3/C4 to study the response-locked components associated with the motor system activity during the performance of this task. Behaviorally, patients showed larger variable errors than controls in synchronizing the frequency of execution of responses to the interstimulus interval, as well as slower responses compared with controls. LT-EEG analysis showed that whereas control participants increased their supplementary motor area (SMA) activity during the preparation of all responses, patients only showed an increment of activity over this area during their first response of the sequence. More interestingly, patients showed a clear increment of the LT-EEG activity associated with SMA shortly after motor responses as compared to the control participants. Finally, patients showed a hand-dependent inhibitory activity over motor areas ipsilateral to the response hand. Overall, our findings reveal drastic differences in the temporal dynamics of the LT-EEG components associated with the activity over motor and premotor cortices in chronic stroke patients compared with matched control participants during alternated hand responses.
Novel MSH6 Mutations in Treatment-Naïve Glioblastoma and Anaplastic Oligodendroglioma Contribute to Temozolomide Resistance Independently of MGMT Promoter Methylation
Authors: Nguyen Stephanie A. , Stechishin Owen D.M. , Luchman H. Artee , Lun Xueqing Q. , Senger Donna L. , Robbins Stephen M. , Cairncross J. Gregory , Weiss Samuel
Published: July 2014

Purpose: The current standard of care for glioblastoma (GBM) involves a combination of surgery, radiotherapy, and temozolomide chemotherapy, but this regimen fails to achieve long-term tumor control. Resistance to temozolomide is largely mediated by expression of the DNA repair enzyme MGMT; however, emerging evidence suggests that inactivation of MSH6 and other mismatch repair proteins plays an important role in temozolomide resistance. Here, we investigate endogenous MSH6 mutations in GBM, anaplastic oligodendroglial tumor tissue, and corresponding brain tumor–initiating cell lines (BTIC).

Experimental Design: MSH6 sequence and MGMT promoter methylation were determined in human tumor samples and BTICs. Sensitivity to temozolomide was evaluated in vitro using BTICs in the absence and presence of O6-benzylguanine to deplete MGMT. The influence of MGMT and MSH6 status on in vivo sensitivity to temozolomide was evaluated using intracranial BTIC xenografts.

Results: We identified 11 previously unreported mutations in MSH6 in nine different glioma samples and six paired BTIC lines from adult patients. In addition, MSH6 mutations were documented in three oligodendrogliomas and two treatment-naïve gliomas, both previously unreported findings. These mutations were found to influence the sensitivity of BTICs to temozolomide both in vitro and in vivo, independent of MGMT promoter methylation status.

Conclusions: These data demonstrate that endogenous MSH6 mutations may be present before alkylator therapy and occur in at least two histologic subtypes of adult glial neoplasms, with this report serving as the first to note these mutations in oligodendroglioma. These findings broaden our understanding of the clinical response to temozolomide in gliomas. Clin Cancer Res; 20(18); 4894–903. ©2014 AACR.
Molecular Pathways: IL11 as a Tumor-Promoting Cytokine—Translational Implications for Cancers
Authors: Ernst Matthias , Putoczki Tracy L.
Published: July 2014

Emerging evidence suggests that cytokines produced by inflammatory cells act as rheostats to link the degree of wounding and local inflammation to epithelial cell survival, proliferation, and metabolism that collectively underpin the repair response. Among these cytokines, the GP130 family, which encompasses, among others, IL6 and IL11, plays a major role in orchestrating these complex processes through the activation of the latent signal transducer and activator of transcription 3 (STAT3) in the epithelium. However, many of the molecular mechanisms that govern and ensure effective epithelial wound healing and regeneration renewal also promote tumorigenesis and the progression of established cancers. Accordingly, GP130 cytokines endow the inflammatory tumor microenvironment with a capacity to promote “cancer hallmark capabilities” of the malignant epithelium, while simultaneously suppressing the antitumor response of innate and adaptive immune cells. Here, we review some recent insights derived from genetic and therapeutic inhibition of the IL6/IL11–GP130–STAT3 signaling cascade in the context of preclinical mouse models of cancer, which are likely to have implications to other solid malignancies. Clin Cancer Res; 20(22); 5579–88. ©2014 AACR.
Cardiac Surgery-Associated Acute Kidney Injury
Authors: Mao Huijuan , Katz Nevin , Ariyanon Wassawon , Blanca-Martos Lourdes , Adýbelli Zelal , Giuliani Anna , Danesi Tommaso Hinna , Kim Jeong Chul , Nayak Akash , Neri Mauro , Virzi Grazia Maria , Brocca Alessandra , Scalzotto Elisa , Salvador Loris , Ronco Claudio
Published: July 2014

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy.
Mycophenolate in Refractory and Relapsing Lupus Nephritis
Authors: Rivera Francisco , Mérida Evangelina , Illescas Maria L. , López-Rubio E. , Frutos Miguel A. , García-Frías Patricia , Ramos Carmela , Sierra María , Baltar José , Lucas Jesús , Oliet Aniana , Vigil Ana , Fernández-Juárez Gema , Segarra Alfons , Praga Manuel ,   on behalf for Glomerular Spanish Glomerular Study Group (GLOSEN)
Published: July 2014

Background: Mycophenolate (MF) is effective as induction and maintenance treatment in patients with lupus nephritis (LN). This study evaluates the efficacy and safety of MF in patients with refractory and relapsing LN. Methods: Data were retrospectively obtained for 85 patients (35 refractory and 50 relapsing) from 11 nephrology departments in Spain. The primary endpoints were the incidence and cumulative number of renal responses and relapses and their relationship with baseline clinical and analytical data. The secondary endpoint was the appearance of side effects. Results: The main clinical and analytical variables were similar both in refractory and relapsing LN. Most of the patients had received cyclophosphamide, and all of them switched to MF. 74 patients (87%) achieved a response (69% partial, 31% complete). Age at starting MF, gender, pathological classification, body mass index, blood pressure, baseline renal function, and proteinuria were not associated with achieving response. After stopping MF, 3 of 19 patients (15.7%) relapsed, all at 6 months of follow-up. No differences were found between clinical and analytical variables and number of relapses. Side effects were unremarkable, except for 1 patient, who died of thrombocytopenia and ovarian hemorrhage. Conclusions: Switching to MF from other immunosuppressive treatments is effective and safe in refractory and relapsing LN.