Comparison of labour induction with misoprostol and dinoprostone and characterization of uterine response based on electrohysterogram

[EN] Objective: The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG). Methods: Two cohorts were defined: misoprostol (25-mg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < ¿ 6. Results: The misoprostol cohort was associated with a shorter time to achieve active labour (p ¿ .017) and vaginal delivery (p ¿ .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17¿1.69, p ¿ .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60¿ after drug administration, while spectral parameters significantly increased after 150¿. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120¿, PMU did so after 180¿, and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug. Conclusion: Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone.This work was partially supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under grant [DPI2015-68397-R] and by the company Bial SA.Benalcazar-Parra, C.; Monfort-Orti, R.; Ye Lin, Y.; Prats-Boluda, G.; Alberola Rubio, J.; Perales Marín, AJ.; Garcia-Casado, J. (2019). Comparison of labour induction with misoprostol and dinoprostone and characterization of uterine response based on electrohysterogram. The Journal of Maternal-Fetal & Neonatal Medicine. 32(10):1586-1594. https://doi.org/10.1080/14767058.2017.1410791S15861594321

Molecular structure and biodegradation kinetics of Linear Alkylbenzene Sulphonates in sea water.

The present paper describes the results of the application of the biodegradation test proposed by the United States Environmental Protection Agency (USEPA) “Biodegradability in sea water” Office of Prevention, Pesticides, and Toxic Substances (OPPTS) 835.3160, to Linear Alkylbenzene Sulphonate (LAS), the synthetic surfactant with the highest consumption volume on a world-wide basis. High performance liquid chromatography (HPLC) has been employed for the separation and quantification of the different homologues and isomers of the surfactant. Water from the Bay of Cádiz (South–West of the Iberian peninsula) has been used as test medium. The results indicate how both lag and t50 time shows a significant linear relationship with the length of the alkyl chain of the homologue; the effect of this is that the homologues of longer chain length not only begin to degrade first but also degrade at a faster rate. Regarding the isomeric composition, it is observed that as the percentage of biodegradation increases, there is an increase in the proportion of internal isomers, in comparison with the isomeric relationships of the original test substanc

Biodegradation kinetics of Linear Alkylbenzene Sulphonates in sea water

This article reports the primary biodegradation kinetics of linear alkylbenzene sulphonates (LAS) in sea water from the Bay of Cadiz (South West of the Iberian Peninsula). The authors used the biodegradation test guideline proposed by the Office of Prevention, Pesticides, and Toxic Substances of the United States Environmental Protection Agency; 835.3160 “Biodegradability in sea water” in its shake flask variant. High performance liquid chromatography (HPLC) has been employed for the analysis of the surfactant material. The surfactant shows a primary biodegradation kinetic in accordance with a logistic model, the kinetic parameters t50 and lag time were calculated by means of a easy quantitative procedure introduced. Mean values of 6.15 ± 0.45 and 6.67 ± 0.6 days were obtained for t50 and lag time, respectively. These results indicate that although LAS has a high primary biodegradation rate in sea water, it biodegrades slower than in similar tests conducted in river water

Mutagenesis-Mediated Virus Extinction: Virus-Dependent Effect of Viral Load on Sensitivity to Lethal Defection

Background: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis. Results: The effect of the mutagenic base analogue 5-fluorouracil (FU) on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV) can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI), or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV), but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV) and encephalomyocarditis virus (EMCV). The increase in mutation frequency and Shannon entropy (mutant spectrum complexity) as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. Conclusions: (i) Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii) This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii) The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv) LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v) The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development. © 2012 Moreno et al.Centro de Biología Molecular Severo Ochoa; Ministerio de Ciencia e Innovación (MICINN); Fundación Ramón ArecesPeer Reviewe

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Polyfunctional T-Cell Responses Are Disrupted by the Ovarian Cancer Ascites Environment and Only Partially Restored by Clinically Relevant Cytokines

Host T-cell responses are associated with favorable outcomes in epithelial ovarian cancer (EOC), but it remains unclear how best to promote these responses in patients. Toward this goal, we evaluated a panel of clinically relevant cytokines for the ability to enhance multiple T-cell effector functions (polyfunctionality) in the native tumor environment.Experiments were performed with resident CD8+ and CD4+ T cells in bulk ascites cell preparations from high-grade serous EOC patients. T cells were stimulated with α-CD3 in the presence of 100% autologous ascites fluid with or without exogenous IL-2, IL-12, IL-18 or IL-21, alone or in combination. T-cell proliferation (Ki-67) and function (IFN-γ, TNF-α, IL-2, CCL4, and CD107a expression) were assessed by multi-parameter flow cytometry. In parallel, 27 cytokines were measured in culture supernatants. While ascites fluid had variable effects on CD8+ and CD4+ T-cell proliferation, it inhibited T-cell function in most patient samples, with CD107a, IFN-γ, and CCL4 showing the greatest inhibition. This was accompanied by reduced levels of IL-1β, IL-1ra, IL-9, IL-17, G-CSF, GM-CSF, Mip-1α, PDGF-bb, and bFGF in culture supernatants. T-cell proliferation was enhanced by exogenous IL-2, but other T-cell functions were largely unaffected by single cytokines. The combination of IL-2 with cytokines engaging complementary signaling pathways, in particular IL-12 and IL-18, enhanced expression of IFN-γ, TNF-α, and CCL4 in all patient samples by promoting polyfunctional T-cell responses. Despite this, other functional parameters generally remained inhibited.The EOC ascites environment disrupts multiple T-cell functions, and exogenous cytokines engaging diverse signaling pathways only partially reverse these effects. Our results may explain the limited efficacy of cytokine therapies for EOC to date. Full restoration of T-cell function will require activation of signaling pathways beyond those engaged by IL-2, IL-12, IL-18, and IL-21

Severe Hindrance of Viral Infection Propagation in Spatially Extended Hosts

The production of large progeny numbers affected by high mutation rates is a ubiquitous strategy of viruses, as it promotes quick adaptation and survival to changing environments. However, this situation often ushers in an arms race between the virus and the host cells. In this paper we investigate in depth a model for the dynamics of a phenotypically heterogeneous population of viruses whose propagation is limited to two-dimensional geometries, and where host cells are able to develop defenses against infection. Our analytical and numerical analyses are developed in close connection to directed percolation models. In fact, we show that making the space explicit in the model, which in turn amounts to reducing viral mobility and hindering the infective ability of the virus, connects our work with similar dynamical models that lie in the universality class of directed percolation. In addition, we use the fact that our model is a multicomponent generalization of the Domany-Kinzel probabilistic cellular automaton to employ several techniques developed in the past in that context, such as the two-site approximation to the extinction transition line. Our aim is to better understand propagation of viral infections with mobility restrictions, e.g., in crops or in plant leaves, in order to inspire new strategies for effective viral control

Informal “Seed” Systems and the Management of Gene Flow in Traditional Agroecosystems: The Case of Cassava in Cauca, Colombia

Our ability to manage gene flow within traditional agroecosystems and their repercussions requires understanding the biology of crops, including farming practices' role in crop ecology. That these practices' effects on crop population genetics have not been quantified bespeaks lack of an appropriate analytical framework. We use a model that construes seed-management practices as part of a crop's demography to describe the dynamics of cassava (Manihot esculenta Crantz) in Cauca, Colombia. We quantify several management practices for cassava—the first estimates of their kind for a vegetatively-propagated crop—describe their demographic repercussions, and compare them to those of maize, a sexually-reproduced grain crop. We discuss the implications for gene flow, the conservation of cassava diversity, and the biosafety of vegetatively-propagated crops in centers of diversity. Cassava populations are surprisingly open and dynamic: farmers exchange germplasm across localities, particularly improved varieties, and distribute it among neighbors at extremely high rates vis-à-vis maize. This implies that a large portion of cassava populations consists of non-local germplasm, often grown in mixed stands with local varieties. Gene flow from this germplasm into local seed banks and gene pools via pollen has been documented, but its extent remains uncertain. In sum, cassava's biology and vegetative propagation might facilitate pre-release confinement of genetically-modified varieties, as expected, but simultaneously contribute to their diffusion across traditional agroecosystems if released. Genetically-modified cassava is unlikely to displace landraces or compromise their diversity; but rapid diffusion of improved germplasm and subsequent incorporation into cassava landraces, seed banks or wild populations could obstruct the tracking and eradication of deleterious transgenes. Attempts to regulate traditional farming practices to reduce the risks could compromise cassava populations' adaptive potential and ultimately prove ineffectual

Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae) and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role

Challenges for Allergy Diagnosis in Regions with Complex Pollen Exposures

Over the past few decades, significant scientific progress has influenced clinical allergy practice. The biological standardization of extracts was followed by the massive identification and characterization of new allergens and their progressive use as diagnostic tools including allergen micro arrays that facilitate the simultaneous testing of more than 100 allergen components. Specific diagnosis is the basis of allergy practice and is always aiming to select the best therapeutic or avoidance intervention. As a consequence, redundant or irrelevant information might be adding unnecessary cost and complexity to daily clinical practice. A rational use of the different diagnostic alternatives would allow a significant improvement in the diagnosis and treatment of allergic patients, especially for those residing in complex pollen exposure areas