New oral anticoagulants and their reversal agents

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

Occurrence of Salmonella spp. in eggs from backyard chicken flocks in Portugal and Romania - results of a preliminary study

The aim of this study was to conduct a preliminary investigation on the occurrence of Salmonella spp. in eggs from chickens raised in backyards in Portugal and Romania. A lack of compliance with safety practices by chicken owners, was demonstrated, especially in Portugal, as 96% of the eggs were visibly dirty and 92.5% were stored at room temperature. In Romania the 202 analysed eggs were Salmonella free, whereas in Portugal six of the 200 eggs sampled were positive for Salmonella spp. (3%). A positive egg for Salmonella spp. was found in 10.7% of the 56 backyard flocks sampled in Portugal. One egg exhibited contamination both in the shellmembrane mixture and in its content, while in the remaining eggs, the pathogen was found either in the shellmembrane (n = 2) or in the yolk and white mixture (n = 3). The serotypes S. Typhimurium (with identical PFGE patterns) and S. Enteritidis were isolated from five eggs and one egg, respectively. Whilst S. Enteritidis was sensitive to the 14 antibiotics tested, S. Typhimurium isolates presented divergent antimicrobial resistant phenotypes and three were classified as multi-drug resistant.info:eu-repo/semantics/acceptedVersio

Life cycle synchronization is a viral drug resistance mechanism

Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus’s life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus’s susceptibility to the direct action of the drug. In this paper, we consider the possibility that a virus population can evolve towards synchronizing its life cycle with the pattern of drug therapy. The periodicity of the drug treatment could then allow for a virus strain whose life cycle length is a multiple of the dosing interval to replicate only when the concentration of the drug is lowest. This process, referred to as “drug tolerance by synchronization”, could allow the virus population to maximize its overall fitness without having to alter drug binding or complete its life cycle in the drug’s presence. We use mathematical models and stochastic simulations to show that life cycle synchronization can indeed be a mechanism of viral drug tolerance. We show that this effect is more likely to occur when the variability in both viral life cycle and drug dose timing are low. More generally, we find that in the presence of periodic drug levels, time-averaged calculations of viral fitness do not accurately predict drug levels needed to eradicate infection, even if there is no synchronization. We derive an analytical expression for viral fitness that is sufficient to explain the drug-pattern-dependent survival of strains with any life cycle length. We discuss the implications of these findings for clinically relevant antiviral strategies

Antibacterial, antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs

Context: Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal. Objective: To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc. Material and methods: Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48 h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24 h) was tested using HEP G2 cells and fibroblasts. Results: Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90mg AAE/g dw and 783.48mg TE/g dw, respectively). CM had the highest zinc concentration (37.21 mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91 mg/100 g dw). LS was rich in rosmarinic acid (301.71 mg/100 g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830 mu g/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content. Conclusion: The most promising plants for further studies are CM, LS and GP.FCT, Fundacao para a Ciencia e a Tecnologia of Portugal [SFRH/BSA/139/2014

Spectrum of the Relativistic Particles in Various Potentials

We extend the notion of Dirac oscillator in two dimensions, to construct a set of potentials. These potentials becomes exactly and quasi-exactly solvable potentials of non-relativistic quantum mechanics when they are transformed into a Schr\"{o}dinger-like equation. For the exactly solvable potentials, eigenvalues are calculated and eigenfunctions are given by confluent hypergeometric functions. It is shown that, our formulation also leads to the study of those potentials in the framework of the supersymmetric quantum mechanics

New type of microengine using internal combustion of hydrogen and oxygen

Microsystems become part of everyday life but their application is restricted by lack of strong and fast motors (actuators) converting energy into motion. For example, widespread internal combustion engines cannot be scaled down because combustion reactions are quenched in a small space. Here we present an actuator with the dimensions 100x100x5 um^3 that is using internal combustion of hydrogen and oxygen as part of its working cycle. Water electrolysis driven by short voltage pulses creates an extra pressure of 0.5-4 bar for a time of 100-400 us in a chamber closed by a flexible membrane. When the pulses are switched off this pressure is released even faster allowing production of mechanical work in short cycles. We provide arguments that this unexpectedly fast pressure decrease is due to spontaneous combustion of the gases in the chamber. This actuator is the first step to truly microscopic combustion engines.Comment: Paper and Supplementary Information (to appear in Scientific Reports

Application of the Nanofiltration Process for Concentration of Polyphenolic Compounds from Geranium robertianum and Salvia officinalis Extracts

The aim of this study was to prove the efficiency of the nanofiltration process for the concentration of polyphenolic compounds from Geranium robertianum and Salvia officinalis extracts and to evaluate the extract’s antioxidant activity. A lab-scale cross-flow set-up using flat-sheet configuration membrane was employed for all experiments. Two nanofiltration membranes have been used: SelRO MPF-36 (Koch membrane) and an organic-inorganic membrane (polysulfone with SBA-15-NH2). When the organic-inorganic membranes were used in the nanofiltration process, the obtained concentrated extracts proved to have higher polyphenol and flavonoid rejections, in both cases (Geranium robertianum and Salvia officinalis). The obtained values were over 88 % DPPH inhibition, for concentrated extracts, using the DPPH method. The concentrated extracts obtained after nanofiltration NF2 (organic-inorganic membrane) had the strongest scavenging activity for all extracts and almost completely inhibited DPPH absorption (92.9 % for Geranium robertianum concentrated extract and 90.1 % for Salvia officinalis concentrated extract). These features turn the studied, concentrated extracts into a good source for further medicinal applications

Induced Parity-Breaking Term at Finite Chemical Potential and Temparature

We exactly calculated the parity-odd term of the effective action induced by the fermions in 2+1 dimensions at finite chemical potential and finite temperature. It shows that gauge invariance is still respected. A more gerneral class of background configurations is considered. The knowledge of the reduced 1+1 determinant is required in order to draw exact conclusions about the gauge invariance of the parity-odd term in this latter case.Comment: 8 pages, LATEX, no figure