G-arylated hydrogen-bonded cyclic tetramer assemblies with remarkable thermodynamic and kinetic stability

The preparation and self-assembly of novel G-C dinucleoside monomers that are equipped with electron-poor aryl groups at the G-N2 amino group have been studied. Such monomers associate via Watson-Crick H-bonding into discrete unstrained tetrameric macrocycles that arise as a thermodynamically and kinetically stabilized product in a wide variety of experimental conditions, including very polar solvent environments and low concentrations. G-arylation produces an increased stability of the cyclic assembly, as a result of a subtle interplay between enthalpic and entropic effects involving the solvent coordination sphereFunding from the European Research Council (ERC-StG 279548) and MINECO (CTQ2011-23659) is gratefully acknowledge

Supramolecular thermoplastics and thermoplastic elastomer materials with self-healing ability based on oligomeric charged triblock copolymers

Supramolecular polymeric materials constitute a unique class of materials held together by non-covalent interactions. These dynamic supramolecular interactions can provide unique properties such as a strong decrease in viscosity upon relatively mild heating, as well as self-healing ability. In this study we demonstrate the unique mechanical properties of phase-separated electrostatic supramolecular materials based on mixing of low molar mass, oligomeric, ABA-triblock copolyacrylates with oppositely charged outer blocks. In case of well-chosen mixtures and block lengths, the charged blocks are phase separated from the uncharged matrix in a hexagonally packed nanomorphology as observed by transmission electron microscopy. Thermal and mechanical analysis of the material shows that the charged sections have a T-g closely beyond room temperature, whereas the material shows an elastic response at temperatures far above this T-g ascribed to the electrostatic supramolecular interactions. A broad set of materials having systematic variations in triblock copolymer structures was used to provide insights in the mechanical properties and and self-healing ability in correlation with the nanomorphology of the materials

The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study

Background Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. Objectives Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. Methods Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. Results People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups’ 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. Conclusions Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty

The role of neuroinflammation in the pathogenesis of epilepsy

Over the past decade, there has been a large amount of evidence indicating neuroendocrine, biochemical, and immune disorders in many acute and chronic central nervous system (CNS) diseases,  including epilepsy, which made the authors consider the  inflammatory theory of epileptogenesis. The chronic inflammatory  process in epilepsy is believed to be facilitated by the activation of  microglia and astrogliosis, which are accompanied by neuronal  damage. The main postulate of this type of investigation is the  assumption that the basis for CNS inflammation is blood-brain barrier (BBB) damage. Cytokines are presumed to play the  greatest role in this process, mainly because they are natural pro-  and anticonvulsants.Patients and methods. Examinations were made in 160 patients with epilepsy (drug-resistant epilepsy (n = 80) and controlled epilepsy (n = 80)) and 30 apparently healthy donors. The blood and  cerebrospinal fluid (CSF) levels of the cytokines interleukin (IL)-1β,  IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), IL-1 receptor  antagonist (IL-1RA), soluble IL-2 receptor (sIL-2R), brain- derived neurotrophic factor (BDNF), S100b protein, С-reactive  protein (CRP), and albumins were analyzed using a solid-phase  enzyme-linked immunoabsorbent assay. Statistical analysis was performed using Student’s t-test and Mann-Whitney U-test.  Differences at p <0.05 were regarded as statistically significant.Results and discussion. The investigation showed that the patients with epilepsy had a substantially impaired plasma cytokine profile: higher levels of proinflammatory cytokines, such as Il-1β, IL-8, and  TNF, and a lower concentration of IL-1 RA. The elevated CSF levels of the cytokines Il-1β and IL8 in patients with epilepsy suggest that  BBB is impaired and a systemic inflammatory process exists while  the absence of IL-1RA indicates that protective inflammation factors  in blood and CSF are reduced

IMMUNE DISTURBANCES IN PATIENTS WITH EPILEPSY AND OPPORTUNITY OF IMMUNOMODULATION BY RECOMBINANT HUMAN IL-2

Abstract: the inflammation in epilepsy pathogenesis is the subjects of scientific discussion. Extensive evidence in favor of the inflammatory theory of epileptogenesis is obtained, according to which epilepsy is a consequence of specialty inflammation in the CNS connected with both the induction of convulsions and their progression. Special attention is paid to cytokines containing in plasma mostly because they are natural pro-convulsants, the markers of inflammation, increased level of which result in higher risk of seizures. Inflammatory factors and mediators such as IL-1 p и TNF can influence on neuron transmission of mediators and promote development of hyper synchronous in neurons and hyper excitation of the brain. The specific role of cytokines IL-1 p in epilepsy is discerning due to it expression in CNS in astrocytes and microglia as a factor of chronic inflammation in CNS. The aim of our study is to evaluate the dynamics of immunological parameters in patients with epilepsy (PE) during the treatment with rIL-2-medicament (Roncoleukinum®), cytokine drug of Interleukins series containing recombinant human Interleukin-2 (rIL-2), which is a structural and functional analog of the endogenous IL-2. The results of the research of specialties of system inflammation response in epileptic patients reveal the increased level of the inflammation markers in plasma and CNS (increased concentration and violation of balance of cytokines of IL-1 p family defined by decrease of RAIL-1 concentration and RAIL-1/IL-1 coefficient). We obtained the data on decrease of content of pro-inflammatory cytokine IL-8 and increase content of BDNF in PE as a result of rIL-2-medicament treatment. Changes of these immunological parameters correlated with clinical improvement of PE: reduction of seizure frequency and positive EEG changes. These results might be used to optimize treatment of PE due to modulation of inflammatory process and increase of neurotrophic factors production required for the processes of brain neuroplasticity and neurogenesis

State of the art for diagnosis and treatment of orthostatic hypotension

This paper presents state of the art of the problem of diagnosis and treatment of orthostatic hypotension (OH). It focuses on the developed algorithms for diagnostics of classical orthostatic hypotension (COH), initial orthostatic hypotension (IOH) and delayed orthostatic hypotension (DOH). It describes the necessary methods for the differential diagnosis of the OH causes. Comparative analysis of the European Society of Cardiology and American College of Cardiology/American Heart Association/Society of Cardiac Rhythm was performed. The treatment options for different groups of patients with orthostatic hypotension are described

COMPARATIVE ANALYSIS OF LOSATAN AND ENALAPRIL ANTIHYPERTENSIVE EFFICACY (ELLA TRIAL)

Aim. To compare antihypertensive efficacy of АТ1 receptors blocker (losartan) and ACE inhibitor (enalapril), including their combinations with hydrochlorothiazide.Material and methods. 60 patients (30-65 y.o.) with arterial hypertension (HT) of stages 1-3 were involved in 12-week opened comparative randomized study. Patients of group-I (n=30) received losartan, patients of group-II (n=30) - enalapril. Blood pressure (BP) changes assessed on the basis of clinical measurements and ambulatory monitoring. Microalbuminuria (MAU) levels, plasma aldosterone levels and plasma renin activity were estimated.Results. Target BP levels were reached in 76,6% of patients in group-I and in 73,3% of patients in group-II. Among patients with moderate HT of stage 2 (n=50) target BP levels were reached in 96% of patients in group-I and in 72% of patients in group-II. Patients of both groups had positive changes in BP levels according to ambulatory BP monitoring. Significant reduction in MAU level and uric acid plasma concentrations were observed.Conclusion. Losartan (Losap, Zentiva) and losartan combination with hydrochlorothiazide (Losap-plus, Zentiva) demonstrated antihypertensive efficacy comparable with this of enalapril as well as nephroprotective features