The Prostanoid 15-Deoxy-D 12,14 -Prostaglangin-J 2 Reduces Lung Inflammation and Protects Mice Against Lethal Influenza Infection

Background. Growing evidence indicates that influenza pathogenicity relates to altered immune responses and hypercytokinemia. Therefore, dampening the excessive inflammatory response induced after infection might reduce influenza morbidity and mortality. Methods. Considering this, we investigated the effect of the anti-inflammatory molecule 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ) in a mouse model of lethal influenza infection. Results. Administration of 15d-PGJ 2 on day 1 after infection, but not on day 0, protected 79% of mice against lethal influenza infection. In addition, this treatment considerably reduced the morbidity associated with severe influenza infection. Our results also showed that treatment with 15d-PGJ 2 decreased influenza-induced lung inflammation, as shown by the diminished gene expression of several proinflammatory cytokines and chemokines. Unexpectedly, 15d-PGJ 2 also markedly reduced the viral load in the lungs of infected mice. This could be attributed to maintained type I interferon gene expression levels after treatment. Interestingly, pretreatment of mice with a peroxisome proliferator-activated receptor gamma (PPARc) antagonist before 15d-PGJ 2 administration completely abrogated its protective effect against influenza infection. Conclusions. Our results demonstrate for the first time that treatment of mice with 15d-PGJ 2 reduces influenza morbidity and mortality through activation of the PPARc pathway. PPARc agonists could thus represent a potential therapeutic avenue for influenza infections

Effect of contact with podiatry in a team approach context on diabetic foot ulcer and lower extremity amputation: systematic review and meta-analysis

Multidisciplinary team (MDT) approach has been shown to reduce diabetic foot ulcerations (DFUs) and lower extremity amputations (LEAs), but there is heterogeneity between team members and interventions. Podiatrists have been suggested as "gatekeepers" for the prevention and management of DFUs. The purpose of our study is to review the effect of podiatric interventions in MDTs on DFUs and LEAs. We conducted a systematic review of available literature. Data's heterogeneity about DFU outcomes made it impossible for us to include it in a meta-analysis, but we identified 12 studies fulfilling inclusion criteria that allowed for them to be included for LEA outcomes. With the exception of one study, all reported favourable outcomes for MDTs that include podiatry. We found statistical significance in favour of an MDT approach including podiatrists for our primary outcome (total LEAs (RR: 0.69, 95% CI 0.54–0.89, I2 = 64%, P = 0.002)) and major LEAs (RR: 0.45, 95% CI 0.23–0.90, I2 = 67%, P < 0.02). Our systematic review, with a standard search strategy, is the first to specifically address the relevant role of podiatrists and their interventions in an MDT approach for DFU management. Our observations support the literature that MDTs including podiatrists have a positive effect on patient outcomes but there is insufficient evidence that MDTs with podiatry management can reduce the risk of LEAs. Our study highlights the necessity for intervention descriptions and role definition in team approach in daily practice and in published literature

Absolute cross section for loss of supercoiled topology induced by 10 eV electrons in highly uniform ∕DNA∕1,3-diaminopropane films deposited on highly ordered pyrolitic graphite.

International audience: It was recently shown that the affinity of doubly charged, 1-3 diaminopropane (Dap(2+)) for DNA permits the growth on highly ordered pyrolitic graphite (HOPG) substrates, of plasmid DNA films, of known uniform thickness [O. Boulanouar, A. Khatyr, G. Herlem, F. Palmino, L. Sanche, and M. Fromm, J. Phys. Chem. C 115, 21291-21298 (2011)]. Post-irradiation analysis by electrophoresis of such targets confirms that electron impact at 10 eV produces a maximum in the yield of single strand breaks that can be associated with the formation of a DNA(-) transient anion. Using a well-adapted deterministic survival model for the variation of electron damage with fluence and film thickness, we have determined an absolute cross section for strand-break damage by 10 eV electrons and inelastic scattering attenuation length in DNA-Dap complex films

Geochemical fingerprints of seawater in the Late Mesoproterozoic Midcontinent Rift, North America : life at the marine-land divide

The 1.1 Ga Midcontinent Rift (MCR) is a thick volcanic-sedimentary succession that forms a curvilinear belt through central North America and crops out along its northern apex around Lake Superior. Sedimentary units of the MCR have been long interpreted as fluvial-lacustrine and invited a number of studies on the early evolution of life in non-marine habitats. One of the key units is the siliciclastic Nonesuch Formation, thought to record deposition in a large lake. However, recent sedimentological observations indicate the presence of marine incursions. To further test this interpretation, we analysed trace element abundances in a broad suite of samples from multiple drill cores through the Nonesuch Formation. We aimed to differentiate geochemical influences of sediment provenance from post-depositional hydrothermal overprint and thereby identify authigenic enrichments in fluid-mobile elements that are indicators of primary environmental conditions. Our results reveal discrete enrichments in Mo and U in organic- and sulphide-rich horizons, which are most parsimoniously interpreted as marine signatures. This conclusion is supported by Sr/Ba ratios, which suggest mixing between freshwater and saltwater, and by rare cm-thick gypsum in the upper Copper Harbor Formation immediately below the Nonesuch rocks. The gypsum displays δ34S values of +25.9 ± 0.6‰, consistent with input of marine sulphate at least during parts of the basin's history. Collectively, our geochemical data support the sedimentological interpretation that this portion of the MCR archives a marine-influenced estuarine system. Although this conclusion rules out that microbial life documented from the MCR was living in exclusively freshwater habitats, the Nonesuch Fm and associated rocks still hold important clues about organisms that were capable of withstanding salinity gradients and bridging the gap between the marine and non-marine environments of the mid-Proterozoic.PostprintPeer reviewe

Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics

Abstract Noncoding markers have a particular appeal as tools for phylogenomic analysis because, at least in vertebrates, they appear less subject to strong variation in GC content among lineages. Thus far, ultraconserved elements (UCEs) and introns have been the most widely used noncoding markers. Here we analyze and study the evolutionary properties of a new type of noncoding marker, conserved nonexonic elements (CNEEs), which consists of noncoding elements that are estimated to evolve slower than the neutral rate across a set of species. Although they often include UCEs, CNEEs are distinct from UCEs because they are not ultraconserved, and, most importantly, the core region alone is analyzed, rather than both the core and its flanking regions. Using a data set of 16 birds plus an alligator outgroup, and ∼3600–∼3800 loci per marker type, we found that although CNEEs were less variable than bioinformatically derived UCEs or introns and in some cases exhibited a slower approach to branch resolution as determined by phylogenomic subsampling, the quality of CNEE alignments was superior to those of the other markers, with fewer gaps and missing species. Phylogenetic resolution using coalescent approaches was comparable among the three marker types, with most nodes being fully and congruently resolved. Comparison of phylogenetic results across the three marker types indicated that one branch, the sister group to the passerine + falcon clade, was resolved differently and with moderate (>70%) bootstrap support between CNEEs and UCEs or introns. Overall, CNEEs appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis

Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon

AbstractObjectives. The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease.Background. Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent.Methods. In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 ± 1.0 mg/liter (low), 8.2 ± 1.8 mg/liter (medium) and 13.2 ± 2.3 mg/liter (high).Results. Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations.Conclusions. It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease

Associations between interarm differences in blood pressure and cardiovascular disease outcomes: protocol for an individual patient data meta-analysis and development of a prognostic algorithm

This is the final version of the article. Available on open access from BMJ Publishing Group via the DOI in this record.There is another record for this publication in ORE: http://hdl.handle.net/10871/32190INTRODUCTION: Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) Is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. METHODS AND ANALYSIS: This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. ETHICS AND DISSEMINATION: This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. PROSPERO REGISTRATION NUMBER: CRD42015031227.National Institute for Health Research (NIHR

Orientability and energy minimization in liquid crystal models

Uniaxial nematic liquid crystals are modelled in the Oseen-Frank theory through a unit vector field $n$. This theory has the apparent drawback that it does not respect the head-to-tail symmetry in which $n$ should be equivalent to -$n$. This symmetry is preserved in the constrained Landau-de Gennes theory that works with the tensor $Q=s\big(n\otimes n- \frac{1}{3} Id\big)$.We study the differences and the overlaps between the two theories. These depend on the regularity class used as well as on the topology of the underlying domain. We show that for simply-connected domains and in the natural energy class $W^{1,2}$ the two theories coincide, but otherwise there can be differences between the two theories, which we identify. In the case of planar domains we completely characterise the instances in which the predictions of the constrained Landau-de Gennes theory differ from those of the Oseen-Frank theory

New antibacterial paper made of silver phosphate cellulose fibers: a preliminary study on the elimination of Staphylococcus aureus involved in diabetic foot ulceration

Aim. To evaluate in vitro the antibacterial effect of a paper made of silver phosphate cellulose fibers (SPCF) on Staphylococcus aureus, the most common diabetic foot ulceration (DFU) pathogen when compared with other common commercial products. Methods. The antibacterial activity of SPCF samples was evaluated through time with cell counting on agar plates. SPCF samples were then compared with commercial wound care products currently in use in DFU treatments (Silvercel™, Acticoat 7, and Aquacel Ag ExtraTM) through time on agar plates (growth inhibition zones). Results. After 6 hours, there was no viable bacterial cell detected on either plate (p < 0.05). There was a net growth inhibition zone for SPCF samples but no significant difference between the two silver concentrations. Compared with common commercial products, SPCF paper provides results equal to Acticoat 7 (p < 0.05) and superior to Aquacel AG ExtraTM and Silvercel™ at lower silver concentrations (p < 0.001). Conclusions. These results have shown the efficiency of SPCF paper to eliminate Staphylococcus aureus in these conditions. SPCF papers are effective when compared with other common commercial products and could have an industrial potential in wound care. Infected DFU could benefit from the antibacterial effectiveness of SPCF, but more relevant experimentations related to foot ulcers are needed