Electrocardiography in hypertensive patients without cardiovascular events: a valuable predictor tool?

Background. Hypertension is an important risk factor of cardiovascular (CV) disease. An early diagnosis of target organ damage could prevent major CV events. Electrocardiography (ECG) is a valuable clinical technique, with wide availability and high speci city, used in evaluation of hypertensive patients. However, the use of ECG as a predictor tool is controversial given its low sensitivity. is study aims to characterise ECG features in a hypertensive population and identify ECG abnormalities that could predict CV events. Methods. We studied 175 hypertensive patients without previous CV events during a follow-up mean of 4.0 ± 2.20 years. ECGs and pulse wave velocity were performed in all patients. Clinical characteristics and ECG abnormalities were evaluated and compared between the patients as they presented CV events. Results. Considering the 175 patients (53.14% male), the median age was 62 years. Median systolic blood pressure was 140 mmHg and diastolic blood pressure was 78 mmHg. Median PWV was 9.8 m/s. Of the patients, 39.4% were diabetic, 78.3% had hyperlipidaemia, and 16.0% had smoking habits. ECG identi ed left ventricular (LV) hypertrophy in 29.71% of the patients, and a LV strain pattern was present in 9.7% of the patients. Twenty-nine patients (16.57%) had a CV event. Comparative analyses showed statistical signi cance for the presence of a LV strain pattern in patients with CV events (p 0.01). Univariate and multivariate analysis con rmed that a LV strain pattern was an independent predictor of CV event (HR 2.66, 95% IC 1.01–7.00). In the survival analysis, the Kaplan–Meier curve showed a worse prognosis for CV events in patients with a LV strain pattern (p 0.014). Conclusion. ECG is a useful daily method to identify end-organ damage in hypertensive patients. In our study, we also observed that it may be a valuable tool for the prediction of CV events.publishe

A CFD study of a pMDI plume spray

Uncorrected proofAsthma is an inflammatory chronic disease characterized by airway obstructions disorders. The treatment is usually done by inhalation therapy, in which pressurized metered-dose inhalers (pMDIs) are preferred devices. The objective of this paper is to characterize and simulate a pMDI spray plume by introducing realistic factors through a computational fluid dynamics (CFD) study. Numerical simulations were performed with Fluent® software, by using a three-dimensional “testbox” for room environment representation. A salbutamol/HFA-134a formulation was used for characterization, whose properties taken as input for the CFD simulations. Spray droplets were considered to be composed by ethanol, salbutamol and HFA-134a. Propellant evaporation was taken into consideration, as well as, drag coefficient correction. Results showed an air temperature drop of 3.3 °C near the nozzle. Also, an increase in air velocity of 3.27 m/s was noticed. The CFD results seem to be in good agreement with Dunbar (1997) data on particle average velocity along the axial distance from the nozzle.National Funds-Portuguese Foundation for Science and Technology, under Strategic Project PEst-C/EME/UI4077/2011 and PEst-OE/EME/299UI0252/201

In Vitro CRISPR/Cas9 Transfection and Gene-Editing Mediated by Multivalent Cationic LiposomeDNA Complexes

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease 9 (Cas9) gene-editing offers exciting new therapeutic possibilities for disease treatment with a genetic etiology such as cancer, cardiovascular, neuronal, and immune disorders. However, its clinical translation is being hampered by the lack of safe, versatile, and effective nonviral delivery systems. Herein we report on the preparation and application of two cationic liposome–DNA systems (i.e., lipoplexes) for CRISPR/Cas9 gene delivery. For that purpose, two types of cationic lipids are used (DOTAP, monovalent, and MVL5, multivalent with +5e nominal charge), along with three types of helper lipids (DOPC, DOPE, and monoolein (GMO)). We demonstrated that plasmids encoding Cas9 and single-guide RNA (sgRNA), which are typically hard to transfect due to their large size (>9 kb), can be successfully transfected into HEK 293T cells via MVL5-based lipoplexes. In contrast, DOTAP-based lipoplexes resulted in very low transfection rates. MVL5-based lipoplexes presented the ability to escape from lysosomes, which may explain the superior transfection efficiency. Regarding gene editing, MVL5-based lipoplexes achieved promising GFP knockout levels, reaching rates of knockout superior to 35% for charge ratios (+/−) of 10. Despite the knockout efficiency being comparable to that of Lipofectamine 3000® commercial reagent, the non-specific gene knockout is more pronounced in MVL5-based formulations, probably resulting from the considerable cytotoxicity of these formulations. Altogether, these results show that multivalent lipid-based lipoplexes are promising CRISPR/Cas9 plasmid delivery vehicles, which by further optimization and functionalization may become suitable in vivo delivery systems.This research was funded by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte and the Project FCOMP-01– 0124-FEDER-021053 (PTDC/SAU-BMA/121028/2010). This research was also supported by the Microfluidic Layer-by-layer Assembly of Cationic Liposome—Nucleic Acid Nanoparticles for Gene Delivery project (032520) co-funded by FCT and the ERDF through COMPETE2020. Diana A. Sousa (D.A.S) and Celso J.O. Ferreira (C.J.O.F) acknowledge FCT for the grants PD/BD/139083/2018 and SFRH/BD/149199/2019, respectively.info:eu-repo/semantics/publishedVersio

A versatile nanocarrierCubosomes, characterization, and applications

The impact of nanotechnology on the exponential growth of several research areas, particularly nanomedicine, is undeniable. The ability to deliver active molecules to the desired site could significantly improve the efficiency of medical treatments. One of the nanocarriers developed which has drawn researchers’ attention are cubosomes, which are nanosized dispersions of lipid bicontinuous cubic phases in water, consisting of a lipidic interior and aqueous domains folded in a cubic lattice. They stand out due to their ability to incorporate hydrophobic, hydrophilic, and amphiphilic compounds, their tortuous internal configuration that provides a sustained release, and the capacity to protect and safely deliver molecules. Several approaches can be taken to prepare this structure, as well as different lipids like monoolein or phytantriol. This review paper describes the different methods to prepare nanocarriers. As it is known, the physicochemical properties of nanocarriers are very important, as they influence their pharmacokinetics and their ability to incorporate and deliver active molecules. Therefore, an extensive characterization is essential to obtain the desired effect. As a result, we have extensively described the most common techniques to characterize cubosomes, particularly nanocarriers. The exceptional properties of the cubosomes make them suitable to be used in several applications in the biomedical field, from cancer therapeutics to imaging, which will be described. Taking in consideration the outstanding properties of cubosomes, their application in several research fields is envisaged.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, by Marie Skłodowska Curie grant (MSCA-RISE; FODIAC; 778388) and by European Regional Development Fund (ERDF) through the Competitiveness factors Operational program—Norte 2020, COMPETE and National Funds through the FCT—under the project AgriFood XXI (NORTE- 01-0145-FEDER-000041). J.L.P. acknowledge the Instituto de Salud Carlos III for a “Sara Borrell” grant (CD19/00250), cofounded by European Social Fund (“El FSE invierte en futuro”). C.J.O.F. acknowledge the FCT for the grant SFRH/149/BD/14199/2019.info:eu-repo/semantics/publishedVersio

Alternative strategies for the extraction of compounds from natural resources

Book of Abstracts of CEB Annual Meeting 2017[Excerpt] Exploitable compounds from natural resources include polysaccharides, proteins and peptides, gum exudates, lipids, polyphenols and other secondary metabolites. Traditional-water extraction (TWE) of polysaccharides is a time-consuming process that requires high solvent and energy consumptions and generates large amounts of waste. Other bioactive compounds are traditionally extracted with organic solvents or mixtures of organic solvents and water, with or without heat. Subcritical water extraction and hydrolysis have been used as an alternative to traditional solvent extraction for many compounds in different matrices (1). Advantages include absence of chemical solvents, lower solvent costs, lower extraction times at moderate operational conditions, resulting in higher quality extracts. Furthermore, water is a solvent with very interesting properties in subcritical conditions. As temperature increases hydrogen bonds break, significantly decreasing the dielectric constant and the polarity, thus increasing solubility of more hydrophobic compounds. On the other hand water ionization increases (thus increasing H+ and OH- ions concentration), meaning that reactions catalysed by acids or bases, like biomass hydrolysis, are accelerated. [...]info:eu-repo/semantics/publishedVersio

Synthesis of novel 1-Aryl-3-[2-,3- Or 4-(Thieno[3,2-b]Pyridin-7-Ylthio)Phenyl]Ureas and evaluation as VEGFR2 Tyrosine kinase inhibitors

Vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase is involved in cancer and in angiogenesis. Herein, we report the synthesis of novel1-aryl-3-[2-, 3- or 4-{thieno[3,2-b ]pyridin-7-ylthio) phenyl]ureas as VEGFR2 inhibitors by promoting the regioselective attack of the thiol group of the 4-aminothiophenol in the chlorine nucleophilic displacement on 7-chlorothieno[3,2-b]pyridine 1, obtaining the aminated compounds Za- c. These were reacted with arylisocyanates to give the corresponding 1,3-diarylureas 3a-c, 4a-c and Sa-c (see scheme).Foundation for the Science and Technology (FCT–Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI- QUI/111060/2009 and the post-Doctoral grant attributed to R.C.C. (SFRH/BPD/68344/2010

PNA-FISH as a new diagnostic method for the determination of clarithromycin resistance of Helicobacter pylori

<p>Abstract</p> <p>Background</p> <p>Triple therapy is the gold standard treatment for <it>Helicobacter pylori </it>eradication from the human stomach, but increased resistance to clarithromycin became the main factor of treatment failure. Until now, fastidious culturing methods are generally the method of choice to assess resistance status. In this study, a new genotypic method to detect clarithromycin resistance in clinical samples, based on fluorescent <it>in situ </it>hybridization (FISH) using a set of peptide nucleic acid probes (PNA), is proposed.</p> <p>Results</p> <p>The set of probes targeting the point mutations responsible for clarithromycin resistance was applied to <it>H. pylori </it>suspensions and showed 100% sensitivity and specificity (95% CI, 79.9-100 and 95% CI, 71.6-100 respectively). This method can also be amenable for application to gastric biopsy samples, as resistance to clarithromycin was also detected when histological slides were tested.</p> <p>Conclusions</p> <p>The optimized PNA-FISH based diagnostic method to detect <it>H. pylori </it>clarithromycin resistance shown to be a very sensitive and specific method for the detection of clarithromycin resistance in the <it>H. pylori </it>smears and also proved to be a reliable method for the diagnosis of this pathogen in clinical samples and an alternative to existing plating methods.</p

On the order of summability of the Fourier inversion formula

In this article we show that the order of the point value, in the sense of Łojasiewicz, of a tempered distribution and the order of summability of the pointwise Fourier inversion formula are closely related. Assuming that the order of the point values and certain order of growth at infinity are given for a tempered distribution, we estimate the order of summability of the Fourier inversion formula. For Fourier series, and in other cases, it is shown that if the distribution has a distributional point value of order k, then its Fourier series is e.v. Cesàro summable to the distributional point value of order k+1. Conversely, we also show that if the pointwise Fourier inversion formula is e.v. Cesàro summable of order k, then the distribution is the (k+1)-th derivative of a locally integrable function, and the distribution has a distributional point value of order k+2. We also establish connections between orders of summability and local behavior for other Fourier inversion problems

Is honey able to potentiate the antioxidant and cytotoxic properties of medicinal plants consumed as infusions for hepatoprotective effects?

Due to the enormous variety of phytochemicals present in plants, their extracts have been used for centuries in the treatment of innumerous diseases, being perceived as an invaluable source of medicines for humans. Furthermore, the combination of different plants was reported as inducing an improved effect (synergism) in comparison to the additive activity of the plants present in those mixtures. Nevertheless, information regarding the effects of plant infusions added with honey is still rather scarce. Accordingly, the aim of this study was evaluating the interaction between chestnut honey, a natural product with well-reported beneficial properties, and three medicinal plants (either as single plant or as combinations of two and three plants), with regard to their antioxidant activity and hepatotoxicity. Antioxidant activity was evaluated by comparing the results from four different assays; the hepatotoxicity was assessed in two different cell lines. Results were compared by analysis of variance and linear discriminant analysis. The addition of honey to the infusions had a beneficial result in both cases, producing a synergistic effect in all samples, except beta-carotene bleaching inhibition for artichoke+milk thistle+honey preparation and also preparations with lower hepatotoxicity, except in the case of artichoke+honey. Moreover, from discriminant linear analysis output, it became obvious that the effect of honey addition overcame that resulting from using single plant or mixed plants based infusions. Also, the enhanced antioxidant activity of infusions containing honey was convoyed by a lower hepatotoxicity.The authors are grateful to Foundation for Science and Technology (FCT, Portugal) for financial support to the research centre CIMO (strategic project PEst-OE/AGR/UI0690/2011) and L. Barros researcher contract under “Programa Compromisso com Ciência – 2008”