Application of a pharmacological transcriptome filter identifies a shortlist of mouse glucocorticoid receptor target genes associated with memory consolidation

Glucocorticoids regulate memory consolidation, facilitating long-term storage of relevant information to adequately respond to future stressors in similar conditions. This effect of glucocorticoids is well-established and is observed in multiple types of behaviour that depend on various brain regions. By and large, higher glucocorticoid levels strengthen event-related memory, while inhibition of glucocorticoid signalling impairs consolidation. The mechanism underlying this glucocorticoid effect remains unclear, but it likely involves the transcriptional effects of the glucocorticoid receptor (GR). We here used a powerful paradigm to investigate the transcriptional effects of GR in the dorsal hippocampus of mice after training in an auditory fear conditioning task, aiming to identify a shortlist of GR target genes associated to memory consolidation. Therefore, we utilized in an explorative study the properties of selective GR modulators (CORT108297 and CORT118335), alongside the endogenous agonist corticosterone and the classical GR antagonist RU486, to pinpoint GR-dependent transcriptional changes. First, we confirmed that glucocorticoids can modulate memory strength via GR activation. Subsequently, by assessing the specific effects of the available GR-ligands on memory strength, we established a pharmacological filter which we imposed on the hippocampal transcriptome data. This identified a manageable shortlist of eight genes by which glucocorticoids may modulate memory consolidation, warranting in-depth follow-up. Overall, we showcase the strength of the concept of pharmacological transcriptome filtering, which can be readily applied to other research topics with an established role of glucocorticoids

New Algorithm to Discriminate Phase Distribution of Gas-Oil-Water Pipe Flow With Dual-Modality Wire-Mesh Sensor

Three-phase gas-oil-water flow is an important type of flow present in petroleum extraction and processing. This paper reports a novel threshold-based method to visualize and estimate the cross-sectional phase fraction of gas-oil-water mixtures. A 16×16 dual-modality wire-mesh sensor (WMS) was employed to simultaneously determine the conductive and capacitive components of the impedance of fluid. Then, both electrical parameters are used to classify readings of WMS into either pure substance (gas, oil or water) or two-phase oil-water mixtures (foam is neglected in this work). Since the wire-mesh sensor interrogates small regions of the flow domain, we assume that the three-phase mixture can be segmented according to the spatial sensor resolution (typically 2–3 mm). Hence, the proposed method simplifies a complex three-phase system in several segments of single or two-phase mixtures. In addition to flow visualization, the novel approach can also be applied to estimate quantitative volume fractions of flowing gas-oil-water mixtures. The proposed method was tested in a horizontal air-oil-water flow loop in different flow conditions. Experimental results suggest that the threshold-based method is able to capture transient three-phase flows with high temporal and spatial resolution even in the presence of water-oil dispersion regardless of the continuous phase

Near-infrared reversible photoswitching of an isolated azobenzene-stilbene dye

Photoswitching of a charged azobenzene-stilbene dye is investigated through laser excitation in a tandem ion mobility mass spectrometer. Action spectra associated with E→Z and Z→E photoisomerisation of the stilbene group exhibit bands at 685 and 440 nm, corresponding to S1←S0 and S3←S0 transitions, respectively. The data suggest that isomers possessing a Z configuration of the azobenzene unit rapidly convert to E isomers and are not discernible using ion mobility spectrometry, and that photoisomerisation occurs through excited state dynamics rather than statistical isomerisation on the ground state potential energy surface

Portuguese multidisciplinary recommendations for non-pharmacological and non-surgical interventions in patients with rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis (RA) report significant levels of disease impact, which are improved, but not fully abrogated by immunosuppressive therapy, even when remission is achieved. This imposes the need for adjuvant interventions targeting the uncontrolled domains of disease impact. Non-pharmacological interventions are widely used for this purpose, but they have not been the object of professional recommendations or guidelines. OBJECTIVE: To propose multidisciplinary recommendations to inform clinical care providers regarding the employment of non-pharmacological and non-surgical interventions in the management of patients with RA. METHODS: The EULAR standardized operating procedures for the development of recommendations were followed. First, a systematic literature review was performed. Then, a multidisciplinary Technical Expert Panel (TEP) met to develop and discuss the recommendations and research agenda. For each developed recommendation i) the level of evidence and grade of recommendation were determined, and ii) the level of agreement among TEP members was set. A recommendation was adopted if approved by ≥75% of the TEP members, and the level of agreement was considered high when ≥8. All relevant national societies were included in this construction process to attain their endorsement. RESULTS: Based on evidence and expert opinion, the TEP developed and agreed on five overarching principles and 12 recommendations for non-pharmacological and non-surgical interventions in patients with RA. The mean level of agreement between the TEP members ranged between 8.5 and 9.9. The recommendations include a broad spectrum of intervention areas, such as exercise, hydrokinesiotherapy, psychological interventions, orthoses, education, general management of comorbidities, among others; and they set the requirements for their application. CONCLUSIONS: These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines and patients' representatives from Portugal. Given the evidence for effectiveness, feasibility and safety, non-pharmacological and non-surgical interventions should be an integral part of standard care for people with RA. It is hoped that these recommendations should be widely implemented in clinical practice. The target audience for these recommendations includes all health professionals involved in the care of patients with RA. The target patient population includes adult Portuguese people with RA.publishersversionpublishe

Dual target strategy: a proposal to mitigate the risk of overtreatment and enhance patient satisfaction in rheumatoid arthritis

Commentary - abstract not available

Score CTo-aBCDE : um novo score preditor de sucesso nas CTOs

© 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Introduction: Patient selection for percutaneous coronary intervention (PCI) in chronic total occlusions (CTOs) is crucial to procedural success. Our aim was to identify independent predictors of success in CTO PCI in order to create an accurate score. Methods: In a single-center observational registry of CTO PCI, demographic and clinical data and anatomical characteristics of coronary lesions were recorded. Linear and logistic regression analysis were used to identify predictors of success. A score to predict success was created and its accuracy was measured by receiver operating curve analysis. Results: A total of 377 interventions were performed (334 patients, age 68±11 years, 75% male). The success rate was 65% per patient and 60% per procedure. Predictors of success in univariate analysis were absence of active smoking (OR 2.02, 95% CI 1.243-3.29; p=0.005), presence of tapered stump (OR 5.2, 95% CI 2.7-10.2; p8 with high probability (95%). Conclusion: In our sample only anatomical characteristics were predictors of success. The creation of a score to predict success, with good accuracy, may enable selection of cases that can be treated by any operator, those in which a dedicated operator will be desirable, and those with an extremely low probability of success, which should be considered individually for conservative management, surgical revascularization or PCI by a team experienced in CTO.info:eu-repo/semantics/publishedVersio

Erythrina velutina Willd. alkaloids : piecing biosynthesis together from transcriptome analysis and metabolite profiling of seeds and leaves

Introduction: Natural products of pharmaceutical interest often do not reach the drug market due to the associated low yields and difficult extraction. Knowledge of biosynthetic pathways is a key element in the development of biotechnological strategies for plant specialized metabolite production. Erythrina species are mainly used as central nervous system depressants in folk medicine and are important sources of bioactive tetracyclic benzylisoquinoline alkaloids (BIAs), which can act on several pathology-related biological targets. Objectives: In this sense, in an unprecedented approach used with a non-model Fabaceae species grown in its unique arid natural habitat, a combined transcriptome and metabolome analyses (seeds and leaves) is presented. Methods: The Next Generation Sequencing-based transcriptome (de novo RNA sequencing) was carried out in a NextSeq 500 platform. Regarding metabolite profiling, the High-resolution Liquid Chromatography was coupled to DAD and a micrOTOF-QII mass spectrometer by using electrospray ionization (ESI) and Time of Flight (TOF) analyzer. The tandem MS/MS data were processed and analyzed through Molecular Networking approach. Results: This detailed macro and micromolecular approach applied to seeds and leaves of E. velutina revealed 42 alkaloids, several of them unique. Based on the combined evidence, 24 gene candidates were put together in a putative pathway leading to the singular alkaloid diversity of this species. Conclusion: Overall, these results could contribute by indicating potential biotechnological targets formodulation of erythrina alkaloids biosynthesis as well as improve molecular databases with omic data from a non-model medicinal plant, and reveal an interesting chemical diversity of Erythrina BIA harvested in Caatinga

An international prospective cohort study evaluating major vascular complications among patients undergoing noncardiac surgery : the VISION Pilot Study

Objectives: Among patients undergoing noncardiac surgery, our objectives were to: (1) determine the feasibility of undertaking a large international cohort study; (2) estimate the current incidence of major perioperative vascular events; (3) compare the observed event rates to the expected event rates according to the Revised Cardiac Risk Index (RCRI); and (4) provide an estimate of the proportion of myocardial infarctions without ischemic symptoms that may go undetected without perioperative troponin monitoring. Design: An international prospective cohort pilot study. Participants: Patients undergoing noncardiac surgery who were >45 years of age, receiving a general or regional anesthetic, and requiring hospital admission. Measurements: Patients had a Roche fourth-generation Elecsys troponin T measurement collected 6 to 12 hours postoperatively and on the first, second, and third days after surgery. Our primary outcome was major vascular events (a composite of vascular death [i.e., death from vascular causes], nonfatal myocardial infarction, nonfatal cardiac arrest, and nonfatal stroke) at 30 days after surgery. Our definition for perioperative myocardial infarction included: (1) an elevated troponin T measurement with at least one of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic electrocardiogram changes, coronary artery intervention, or cardiac imaging evidence of myocardial infarction; or (2) autopsy findings of acute or healing myocardial infarction. Results: We recruited 432 patients across 5 hospitals in Canada, China, Italy, Colombia, and Brazil. During the first 30 days after surgery, 6.3% (99% confidence interval 3.9–10.0) of the patients suffered a major vascular event (10 vascular deaths, 16 nonfatal myocardial infarctions, and 1 nonfatal stroke). The observed event rate was increased 6-fold compared with the event rate expected from the RCRI. Of the 18 patients who suffered a myocardial infarction, 12 (66.7%) had no ischemic symptoms to suggest myocardial infarction. Conclusions: This study suggests that major perioperative vascular events are common, that the RCRI underestimates risk, and that monitoring troponins after surgery can assist physicians to avoid missing myocardial infarction. These results underscore the need for a large international prospective cohort study

Green manure in coffee systems in the region of Zona da Mata, Minas Gerais: characteristics and kinetics of carbon and nitrogen mineralization.

The use of green manure may contribute to reduce soil erosion and increase the soil organic matter content and N availability in coffee plantations in the Zona da Mata, State of Minas Gerais, in Southeastern Brazil. The potential of four legumes (A. pintoi, C. mucunoides, S. aterrimum and S. guianensis)to produce above-ground biomass, accumulate nutrients and mineralize N was studied in two coffee plantations of subsistence farmers under different climate conditions. The biomass production of C. mucunoides was influenced by the shade of the coffee plantation.C. mucunoides tended to mineralize more N than the other legumes due to the low polyphenol content and polyphenol/N ratio. In the first year, the crop establishment of A. pintoi in the area took longer than of the other legumes, resulting in lower biomass production and N2 fixation. In the long term, cellulose was the main factor controlling N mineralization. The biochemical characteristics, nutrient accumulation and biomass production of the legumes were greatly influenced by the altitude and position of the area relative to the sun

Targeting the Immune System with Plant Lectins to Combat Microbial Infections

The arsenal of drugs available to treat infections caused by eukaryotic and prokaryotic microbes has been declining exponentially due to antimicrobial resistance phenomenon, leading to an urgent need to develop new therapeutic strategies. Host-directed immunotherapy has been reported as an attractive option to treat microbial infections. It consists in the improvement of host defenses by increasing the expression of inflammatory mediators and/or controlling of inflammation-induced tissue injury. Although the in vitro antimicrobial and immunomodulatory activities of lectins have been extensively demonstrated, few studies have evaluated their in vivo effects on experimental models of infections. This review aims to highlight the experimental use of immunomodulatory plant lectins to improve the host immune response against microbial infections. Lectins have been used in vivo both prophylactically and therapeutically resulting in the increased survival of mice under microbial challenge. Other studies successfully demonstrated that lectins could be used in combination with parasite antigens in order to induce a more efficient immunization. Therefore, these plant lectins represent new candidates for management of microbial infections. Furthermore, immunotherapeutic studies have improved our knowledge about the mechanisms involved in host–pathogen interactions, and may also help in the discovery of new drug targets