MMP-9, TIMP-1 and S100B protein as markers of ischemic stroke in patients after carotid artery endarterectomy.

Ischemic stroke is the main cause of permanent disability in adult patients. No commonly accepted method were discovered to predict stroke before the first symptoms. Activation of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and S100B protein may be observe in patients with symptomatic carotid artery stenosis. Hemorrhagic transformation of ischemic stroke may be associated with changes in MMP, TIMP and S100B. AIM: The aim of this study was to determine if MMP-9, TIMP-1 and S-100B protein may markers of forthcoming ischemic stroke in patients undergoing carotid endarterectomy. MATERIALS AND METHODS: Blood samples were taken and an analysis of circulating proteins (MMP-9, TIMP-1, S100B) 73 subsequent patients with carotid artery stenosis ≥70% (33 asymptomatic and 40 symptomatic), who were referred for potential revascularization. RESULTS: A statistically significant difference was found between MMP- 9 levels in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy. Also, average TIMP-1 levels in patients with ischemic stroke and stenosis ≥70% were statistically significantly higher than the average levels in patients after endarterectomy. In terms of S-100B, a higher mean value was observed in patients with stroke than in endarterectomy group. No statistical differences were found in the levels of that proteins in the hemorrhagic transformation of ischemic stroke. CONCLUSIONS: Increased levels of MMP-9, TIMP-1 and S-100B in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy showed that abovementioned proteins may be a good predictive factor of ischemic stroke in patients undergoing carotid endarterectomy.

Tempel: time-series mutation prediction of influenza A viruses via attention-based recurrent neural networks.

MOTIVATION: Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. The goal of this work is to predict whether mutations are likely to occur in the next flu season using historical glycoprotein hemagglutinin sequence data. One of the major challenges is to model the temporality and dimensionality of sequential influenza strains and to interpret the prediction results. RESULTS: In this article, we propose an efficient and robust time-series mutation prediction model (Tempel) for the mutation prediction of influenza A viruses. We first construct the sequential training samples with splittings and embeddings. By employing recurrent neural networks with attention mechanisms, Tempel is capable of considering the historical residue information. Attention mechanisms are being increasingly used to improve the performance of mutation prediction by selectively focusing on the parts of the residues. A framework is established based on Tempel that enables us to predict the mutations at any specific residue site. Experimental results on three influenza datasets show that Tempel can significantly enhance the predictive performance compared with widely used approaches and provide novel insights into the dynamics of viral mutation and evolution. AVAILABILITY AND IMPLEMENTATION: The datasets, source code and supplementary documents are available at: https://drive.google.com/drive/folders/15WULR5__6k47iRotRPl3H7ghi3RpeNXH. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of mountain ultra-marathon running on plasma angiopoietin-like protein 4 and lipid profile in healthy trained men.

PURPOSE: Angiopoietin-like protein 4 (ANGPTL4) regulates lipid metabolism by inhibiting lipoprotein lipase activity and stimulating lipolysis in adipose tissue. The aim of this study was to find out whether the mountain ultra-marathon running influences plasma ANGPTL4 and whether it is related to plasma lipid changes. METHODS: Ten healthy men (age 31 ± 1.1 years) completed a 100-km ultra-marathon running. Plasma ANGPTL4, free fatty acids (FFA), triacylglycerols (TG), glycerol (Gly), total cholesterol (TC), low (LDL-C) and high (HDL-C) density lipoprotein-cholesterol were determined before, immediately after the run and after 90 min of recovery. RESULTS: Plasma ANGPTL4 increased during exercise from 68.0 ± 16.5 to 101.2 ± 18.1 ng/ml (p < 0.001). This was accompanied by significant increases in plasma FFA, Gly, HDL-C and decreases in plasma TG concentrations (p < 0.01). After 90 min of recovery, plasma ANGPTL4 and TG did not differ significantly from the exercise values, while plasma FFA, Gly, TC and HDL-C were significantly lower than immediately after the run. TC/HDL-C and TG/HDL-C molar ratios were significantly reduced. The exercise-induced changes in plasma ANGPTL4 correlated positively with those of FFA (r = 0.73; p < 0.02), and HDL-C (r = 0.69; p < 0.05). Positive correlation was found also between plasma ANGPTL4 and FFA concentrations after 90 min of recovery (r = 0.77; p < 0.01). CONCLUSIONS: The present data suggest that increase in plasma FFA during mountain ultra-marathon run may be involved in plasma ANGPTL4 release and that increase in ANGPTL4 secretion may be a compensatory mechanism against fatty acid-induced oxidative stress. Increase in plasma HDL-C observed immediately after the run may be due to the protective effect of ANGPTL4 on HDL.

Brain Functional Reserve in the Context of Neuroplasticity after Stroke.

Stroke is the second cause of death and more importantly first cause of disability in people over 40 years of age. Current therapeutic management of ischemic stroke does not provide fully satisfactory outcomes. Stroke management has significantly changed since the time when there were opened modern stroke units with early motor and speech rehabilitation in hospitals. In recent decades, researchers searched for biomarkers of ischemic stroke and neuroplasticity in order to determine effective diagnostics, prognostic assessment, and therapy. Complex background of events following ischemic episode hinders successful design of effective therapeutic strategies. So far, studies have proven that regeneration after stroke and recovery of lost functions may be assigned to neuronal plasticity understood as ability of brain to reorganize and rebuild as an effect of changed environmental conditions. As many neuronal processes influencing neuroplasticity depend on expression of particular genes and genetic diversity possibly influencing its effectiveness, knowledge on their mechanisms is necessary to understand this process. Epigenetic mechanisms occurring after stroke was briefly discussed in this paper including several mechanisms such as synaptic plasticity; neuro-, glio-, and angiogenesis processes; and growth of axon.

The Role of Oral Cavity Biofilm on Metallic Biomaterial Surface Destruction-Corrosion and Friction Aspects.

Metallic biomaterials in the oral cavity are exposed to many factors such as saliva, bacterial microflora, food, temperature fluctuations, and mechanical forces. Extreme conditions present in the oral cavity affect biomaterial exploitation and significantly reduce its biofunctionality, limiting the time of exploitation stability. We mainly refer to friction, corrosion, and biocorrosion processes. Saliva plays an important role and is responsible for lubrication and biofilm formation as a transporter of nutrients for microorganisms. The presence of metallic elements in the oral cavity may lead to the formation of electro-galvanic cells and, as a result, may induce corrosion. Transitional microorganisms such as sulfate-reducing bacteria may also be present among the metabolic microflora in the oral cavity, which can induce biological corrosion. Microorganisms that form a biofilm locally change the conditions on the surface of biomaterials and contribute to the intensification of the biocorrosion processes. These processes may enhance allergy to metals, inflammation, or cancer development. On the other hand, the presence of saliva and biofilm may significantly reduce friction and wear on enamel as well as on biomaterials. This work summarizes data on the influence of saliva and oral biofilms on the destruction of metallic biomaterials.

Artificial Mucin-based Saliva Preparations - Physicochemical and Tribological Properties.

PURPOSE: To create and investigate artificial mucin-based saliva substitutes with properties similar to natural saliva. MATERIALS AND METHODS: Natural saliva and six saliva preparations were tested. Saliva substitutes were made using phosphate buffered saline (PBS) prepared in deionised water or plasma-treated water (PBSPT) with addition of porcine gastric mucin and guar gum or poloxamer 407. A wide range of properties were characterised: physicochemical (changes of pH, conductivity and surface tension over time: 1, 24, 96, 168 h after mixing ingredients), rheological (viscosity and viscoelasticity), tribological (coefficient of friction for titanium alloy Ti-6Al-7Nb kinematic couple) and corrosive (open circuit potential, corrosion potential, polarisation resistance). RESULTS: Saliva preparations based only on mucin had pH, viscosity, coefficient of friction and corrosion parameters similar to those of natural saliva. Guar gum increased the values of viscosity, viscoelasticity and the coefficient of friction. Similar results were obtained for poloxamer 407, whereas it decreased the surface tension of tested preparations. Plasma-treated PBS enhanced the corrosion resistance of saliva substitutes with guar gum and poloxamer 407. CONCLUSION: Among the tested compositions, saliva substitutes based only on mucin were found to have parameters similar to human whole saliva. Mucin saliva preparations may have wide applicability for patients with e.g. xerostomia or patients using a metal prosthesis.

Rheological and tribological behavior of polyacrylamide-base solutions for artificial synovial fluid.

PURPOSE: This paper presents tribological and rheological analysis results of artificial synovial fluid base solutions. Special attention was paid to polyacrylamide preparations with different molecular weights and concentrations. METHODS: Tribological tests were conducted using the Al2O3-CoCrMo friction pair in the presence of investigated lubricants. Confocal microscopy was used to analyze and assess of volume, depth, and width of wear traces. Moreover, the viscosity and viscoelasticity tests of analyzed solutions were carried out. The rheological measurements were focused on the oscillatory tests, which allowed us to determine the elasticity modulus (G') and viscosity (G″). RESULTS: Viscoelastic nature of the tested preparations depends on the strain rate. It has been shown that elastic properties dominate at higher frequencies. The molecular weight of the polymer has a particular influence on these properties. The most promising results were obtained for 6% and 8 % high molecular weight polyacrylamide compositions. CONCLUSIONS: However, all tested polyacrylamide solutions show better rheological and tribological characteristics than commercial preparation based on hyaluronic acid.

Region-based epigenetic clock design improves RRBS-based age prediction.

Recent studies suggest that epigenetic rejuvenation can be achieved using drugs that mimic calorie restriction and techniques such as reprogramming-induced rejuvenation. To effectively test rejuvenation in vivo, mouse models are the safest alternative. However, we have found that the recent epigenetic clocks developed for mouse reduced-representation bisulphite sequencing (RRBS) data have significantly poor performance when applied to external datasets. We show that the sites captured and the coverage of key CpGs required for age prediction vary greatly between datasets, which likely contributes to the lack of transferability in RRBS clocks. To mitigate these coverage issues in RRBS-based age prediction, we present two novel design strategies that use average methylation over large regions rather than individual CpGs, whereby regions are defined by sliding windows (e.g. 5 kb), or density-based clustering of CpGs. We observe improved correlation and error in our regional blood clocks (RegBCs) compared to published individual-CpG-based techniques when applied to external datasets. The RegBCs are also more robust when applied to low coverage data and detect a negative age acceleration in mice undergoing calorie restriction. Our RegBCs offer a proof of principle that age prediction of RRBS datasets can be improved by accounting for multiple CpGs over a region, which negates the lack of read depth currently hindering individual-CpG-based approaches.

Predictors of COVID-19 Hospital Treatment Outcome.

BACKGROUND: There are more than 228,394,572 confirmed cases and 4,690,186 confirmed deaths caused by COVID-19 worldwide. The magnitude of the COOVID-19 pandemic has stimulated research on the treatment and diagnosis of COVID-19 patients. OBJECTIVE: In this report, a battery of specific parameters was used to develop a model that allows prediction of the outcome of the COVID-19 treatment. These parameters are C-reactive protein, procalcitonin, fibrinogen, D-dimers, immature granulocytes, and interleukin-6. METHODS: The study was carried out on a sample of N = 49 survivors (22 men, 27 women) and 83 deceased patients (62 men, 21 women). The distribution of means and differences in means of the parameters studied between survivors and deceased patients were evaluated using the bootstrap method. RESULTS: A mathematical model that allows for the prediction of hospitalization outcome was obtained using the Naive Bayes model. The results demonstrated a statistically significant difference between survivors and deceased patients in all parameters studied. A mathematical model employing a battery of parameters provided a 97% precision in predicting the outcome of hospitalization. CONCLUSION: This study showed that the cross-correlation of survivability with absolute levels of C-reactive protein, procalcitonin, fibrinogen, D-dimers, immature granulocytes, and interleukin-6 could be used successfully in the hospital setting as a diagnostic tool.

Effects of growth hormone and insulin-like growth factor-I on the iron-induced lipid peroxidation in the rat liver and porcine thyroid homogenates.

OBJECTIVES: Growth hormone (GH) and its tissue mediator, insulin-like growth factor-I (IGF-I), are involved in oxidative processes, lipid peroxidation (LPO) included. Bivalent iron (Fe2+) is frequently used to experimentally induce oxidative damage to macromolecules (Fe2++H2O2+H+→Fe3++•OH+H2O). The aim of the study was to evaluate the effect of GH and/or IGF-I on the iron-induced LPO in the rat liver and porcine thyroid homogenates. METHODS: Rat liver and porcine thyroid homogenates were incubated in presence of GH (100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001 µg/ml) or IGF-I (1000; 100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001 µg/ml) or GH (100 µg/ml)+IGF-I, or FeSO4+H2O2 plus GH and/or IGF-I. The level of LPO was expressed as concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) per mg of protein. RESULTS: GH and/or IGF-I did not change the basal level of oxidative damage to lipids. In the rat liver homogenates, GH did not affect the iron-induced LPO, whereas IGF-I--in the lowest two concentrations--enhanced the process. In porcine thyroid homogenates, GH--in its two lowest concentrations--prevented, whereas in other concentrations, it enhanced the iron-induced LPO. IGF-I, in all used concentrations, enhanced the iron-induced LPO. CONCLUSION: GH and/or IGF-I may reveal prooxidative effects. This fact does not support their application in the treatment of disorders associated with increased oxidative damage.

Specialist thyroid package 1 (PS1) in outpatient endocrine care [Pakiet specjalistyczny dotyczacy tarczycy (PS1) w ambulatoryjnej opiece endokrynologicznej].

The article presents the assumptions of a new specialist thyroid package (PS1) in outpatient specialist care in the field of endocrinology, which was introduced by the National Health Fund (NFZ - Narodowy Fundusz Zdrowia) from January 2020. It became an impulse to characterize the current problems affecting specialist care in the field of endocrinology, search for their potential causes and propose strategies that are intended to contribute to increasing the efficiency of the system.

Fretting and Fretting Corrosion Processes of Ti6Al4V Implant Alloy in Simulated Oral Cavity Environment.

The paper presents the results of in vitro studies of fretting and fretting corrosion processes of Ti6Al4V implant alloy in the environment of natural saliva and self-made mucin-based artificial saliva solutions. The study was performed on a specially designed fretting pin-on-disc tester, which was combined with a set used for electrochemical research. The open circuit potential measurements and potentiodynamic method were used for corrosion tests. The worn surfaces were subjected to microscopic observations and an evaluation of wear. Results were interpreted using the dissipated energy and third-body approaches. The X-ray diffraction analysis showed that titanium oxides constitute over 80% of the friction products. Special attention was paid to the role of saliva and its substitutes, which in certain cases can lead to the intensification of fretting wear. On the basis of the received results, a new phenomenological model of fretting corrosion processes was proposed. This model involves the formation of an abrasive paste that is a combination of metal oxides and the organic components of saliva.

Changes in the Hormonal Profile of Athletes following a Combat Sports Performance.

RESULTS: Following fighting, the adrenaline concentration was significantly higher in all athletes, most markedly in K (p < 0.001). Baseline cortisol and BDNF levels did not differ among the groups and rose significantly in all the groups after the performance. Baseline testosterone concentration was slightly higher in K than in JSW and rose in all the groups to reach similar levels; the increase in T was significantly higher than in K. CONCLUSIONS: Despite substantial differences in the characteristics of the combat sports investigated, including the type of physical effort and the required balance between restraint and aggression, the performance in each of them gives rise to similar hormonal changes with a possible exception of karate showing higher stress hormone levels.

Overview and Analysis of the Cost of Drug Programs in Poland: Public Payer Expenditures and Coverage of Cancer and Non-Neoplastic Diseases Related Drug Therapies from 2015-2018 Years.

BACKGROUND: In Poland drug programmes developed by the Minister of Health and financed by the National Health Fund are special reimbursement frameworks of innovative, expensive, and mostly hospital based medical products used for a small number of patients. RESEARCH DESIGN: The research presented in this paper is based on data analysis published by the National Health Fund in Poland. The analysis focused on estimating public payer expenditure on drugs available within drug programmes from 2015 to 2018. RESULTS: In subsequent years, reimbursement of drugs used within drug programmes was associated with the National Health Fund budget expenditure of 635 mln USD, 755 mln USD, 854 mln USD, and 921 mln USD, respectively. Reimbursement of oncology drug programmes constituted 48.1%, 42.5%, 47.1%, and 52.4% and were approximately 305, 312, 402, 483 mln USD, whereas values of non-oncology drug programmes were approximately 330, 434, 452, and 438 mln USD which constituted 51.9%, 57.5%, 52.9%, and 47.6% respectively. CONCLUSION: Despite the fact that the expenditure on drug programs in Poland are increasing every year, they undoubtedly improve the patient's access to the most innovative oncological and nononcological therapies in the Polish healthcare system.

[Cytostatic and cytotoxic waste - rules of conduct in Poland]. / Odpady cytostatyczne i cytotoksyczne ­ zasady postepowania w Polsce.

Poland is one of the European countries with the highest level of production of dangerous medical waste. Although in Europe the volume of produced cytotoxic and cytostatic waste (used in chemotherapy by oncological patients) has been declining for several years, in Poland a reverse trend has been observed. As this waste puts the safety of medical workers and patients at risk, special handling procedures are required to limit the harmful effect of these drugs on human health. In view of the above, the aim of the work was to present the rules of conduct with cytotoxic and cytostatic drugs, and their waste, in Poland. Med Pr. 2019;70(3):377-91.

Glutathione Metabolism, Mitochondria Activity, and Nitrosative Stress in Patients Treated for Mandible Fractures.

The aim of the study was to evaluate the effect of titanium bone fixations on mitochondrial activity, reactive oxygen species (ROS) production, glutathione metabolism, and selected markers of oxidative/nitrosative stress in the periosteum-like tissue of patients treated with mandible fractures. The study group consisted of 30 patients with bilateral fractures of the mandible body eligible for surgical treatment. Our study is the first one that indicates disturbances of mitochondrial activity as well as a higher production of ROS in the periosteum-like tissue covering titanium fixations of the mandible. We also found significantly higher levels of reduced glutathione and enhanced activity of glutathione reductase in the periosteum homogenates of patients in the study group compared to the control group. Levels of nitrosative (S-nitrosothiols, peroxynitrite, nitrotyrosine) and oxidative stress biomarkers (malondialdehyde, protein carbonyls, dityrosine, kynurenine, and N-formylkynurenine) were statistically elevated in periosteum-like tissue covering titanium fixations. Although exposure to titanium fixations induces local antioxidant mechanisms, patients suffer oxidative damage, and in the periosteum-like tissue the phenomenon of metallosis was observed. Titanium implants cause oxidative/nitrosative stress as well as disturbances in mitochondrial activity.

Protective effects of GH and IGF-I against iron-induced lipid peroxidation in vivo.

Iron overload may enhance oxidative damage. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are involved in oxidative processes, lipid peroxidation (LPO) included. The aim of the study was to evaluate the in vivo effects of GH, IGF-I and/or iron on LPO in rat tissues. Male Wistar rats were administered iron (Fe2+; 3mg/100g b.w., i.p., on the 8th day) and/or GH (0.2IU/100g b.w.), and/or IGF-I (2microg/100g b.w.) once daily for 8 days. LPO products (malondialdehyde+4-hydroxyalkenals) were measured in rat brain, lung, small intestine, liver, kidney, testis, spleen and serum. Iron injection increased LPO only in the small intestine and that effect was completely prevented by either GH or IGF-I. In the brain, GH decreased, whereas IGF-I increased, the basal LPO. GH and IGF-I possess some ability to prevent iron-induced oxidative damage in iron sensitive tissues, but contribute to oxidative imbalance in other tissues.

TiC-composite materials in applications for kinematic denture connections.

PURPOSE: This paper presents an own proposal for the construction of a ball latch intended for use in prosthetic dentistry. Attention was paid to the existing commercial constructions of elements of the same type, indicating their advantages and disadvantages. Based on the analysis of the present solutions, own ones were proposed. MATERIALS AND METHODS: The following materials were chosen for the tests: pure titanium, 316 L V steel, Ti15Mo2.8Nb obtained using powder metallurgy and through mechanical alloying, 10 and 20% of titanium carbide - obtained using powder metallurgy, as well as 10 and 20% of graphite - obtained using powder metallurgy. For the prepared materials, tribological tests were performed using a friction simulator in a ring/shield system. RESULTS: Fairly extensive tests were performed to verify the suitability of the selected material for use in the specific conditions of the oral cavity. The performed tests showed that the proposed material is not only beneficial in relation to the existing commercial dental alloys but also meets the general criteria set for this type of elements. CONCLUSIONS: A more beneficial use of two-part ball latches (two key parts - patrix, matrix) was noticed in comparison to latches consisting of three parts (patrix, insert, matrix). On the basis of the obtained test results, it can be concluded that the proposed own design of a ball latch is a good alternative for traditional constructional and material solutions of commercial ball latches.

Psychomotor performance of Polish Air Force cadets after 36 hours of survival training.

INTRODUCTION: The preparation of Polish Air Force cadets for survival in isolation is a necessary element of their training, to demonstrate just how difficult can be the conditions they could encounter in a combat situation. Objective. The aim of the research was to assess the effect of long-term survival training on selected coordination motor skills in Air Force cadets. MATERIAL AND METHODS: Fifteen air force cadets aged 19.6±0.3 years exercised for 36 hours during survival training without the possibility to sleep. They were examined 4 times: Day 1 - before effort (training), Day 2 - after 24 hours training, Day 3 - directly after 36 hours training, Day 4 - next day, after an all night rest. They were examined for shooting and reaction time, the ability to maintain body balance, running motor adjustment, handgrip force differentiation, and on Days 1 and 3, exercise capacity was evaluated with a 1 mile walking test. RESULTS: The survival training resulted in significant decreases in maximum handgrip strength, corrected 50% max handgrip, maintenance of body balance and heart rate. No changes occurred in reaction time, running motor adjustment and shooting performance. Overnight rest did not result in recovery of any of the examined factors to the values observed on Day 1. CONCLUSIONS: Survival training combined with sleep deprivation mostly affected peripheral factors depending on strong action from both muscles and nervous system, whereas complex tasks involving short-term central alertness and moderate exertion were maintained. In order to improve performance, more endurance strength training, if possible combined with sleep deprivation, should be introduced in military training.

Use of magnetic nanoparticles as a drug delivery system to improve chlorhexidine antimicrobial activity.

Nanotechnology offers new tools for developing therapies to prevent and treat oral infections, particularly biofilm-dependent disorders, such as dental plaques and endodontic and periodontal diseases. Chlorhexidine (CHX) is a well-characterized antiseptic agent used in dentistry with broad spectrum activity. However, its application is limited due to inactivation in body fluid and cytotoxicity toward human cells, particularly at high concentrations. To overcome these limitations, we synthesized nanosystems composed of aminosilane-coated magnetic nanoparticles functionalized with chlorhexidine (MNP@CHX). In the presence of human saliva, MNPs@CHX displayed significantly greater bactericidal and fungicidal activity against planktonic and biofilm-forming microorganisms than free CHX. In addition, CHX attached to MNPs has an increased ability to restrict the growth of mixed-species biofilms compared to free CHX. The observed depolarization of mitochondria in fungal cells treated with MNP@CHX suggests that induction of oxidative stress and oxidation of fungal structures may be a part of the mechanism responsible for pathogen killing. Nanoparticles functionalized by CHX did not affect host cell proliferation or their ability to release the proinflammatory cytokine, IL-8. The use of MNPs as a carrier of CHX has great potential for the development of antiseptic nanosystems.