Репозиторий Университета

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Hydrophobic segments made of oligo(l,l- or d,l-lactides) or poly(l,l-lactide) are grafted onto chitosan backbone in order to use their amphiphilic behavior to prepare degradable microcarriers intended to be used for tissue engineering. Hydrophilic–lipophilic balance of these copolymers is adjusted playing on the respective length of their hydrophilic and hydrophobic moieties. Thanks to their self-emulsifying properties, these graft copolymers are processed into microspheres in the absence of hydrophilic emulsifier commonly added in the aqueous phase of the oil/water emulsion. The copolymers containing amorphous oligolactide segments of medium length are demonstrated to be the most effective ones for microparticle fabrication. The microparticles are characterized using SEM, EDX, and FTIR. The reactivity of amine group is demonstrated using fluorescein isothiocyanate staining. The resulting microspheres disclose a porous core and a shell enriched by the hydrophilic polysaccharide moieties. Stabilization of the oil/water interface during the microsphere fabrication, total yield, size distribution, and microparticle surface morphology are mainly affected by the macromolecular features of the copolymers.

© 2019 Background: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient's condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA. Methods: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years). Results: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy. Conclusion: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly attributed to excessive product formation. Underrated so far is, however, that HO may exert effects additionally via modulation of the cellular heme levels. Heme, besides being an often-quoted generator of oxidative stress, plays also an important role as a signaling molecule. Heme controls the anti-oxidative defense, circadian rhythms, activity of ion channels, glucose utilization, erythropoiesis, and macrophage function. This broad spectrum of effects depends on its interaction with proteins ranging from transcription factors to enzymes. In degrading heme, HO has the potential to exert effects also via modulation of heme-mediated pathways. In this review, we will discuss the multitude of pathways regulated by heme to enlarge the view on HO and its role in cell physiology. We will further highlight the contribution of HO to pathophysiology, which results from a dysregulated balance between heme and the degradation products formed by HO.

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Nanoporous glassy polymers are perspective materials for the fabrication of gas separation membranes, especially for the application of gaseous hydrocarbon separation. However, the drawback of such materials is the pronounced physical aging resulting in the dramatic drop of gas transport properties due to relaxation of high-free-volume fraction in time. Herein, a novel and readily available group of such glassy polymers is reported based on 5-alkylnorbornenes. These polymers are easily synthesized from dicyclopentadiene and α-olefins by Diels-Alder reaction and vinyl (addition) polymerization of the formed cycloadducts in the presence of ([(η3-C3H5)PdCl]2/PCy3/Na+[B(3,5-(CF3)2C6H3)4]− catalyst. The obtained polymers display low-fraction free volume, stable gas permeability over time, and possess a unique feature for the glassy polymers—solubility controlled permeation of hydrocarbons and enhanced C4H10/CH4 selectivity.

© 2019, Ecozone, OAIMDD. All rights reserved. Spirituality is the fourth aspect of health, along with the physical, mental and social ones. At the same time, religiosity is a private manifestation of spirituality. The purpose of the study is to find out the relationship between health care on the one hand, and spirituality, religious life, a subjective feeling of happiness and good health indicators, on the other. A review of literary sources shows that positive values, beliefs, and the power of faith contribute to health and happiness. Religious participation and spiritual practices have a positive effect on the survival of the sick, low disease incidence, prolonged remissions of chronic diseases, lower anxiety and depression level, healthy lifestyle and compliance. At the same time, better results in treating patients are achieved when doctors and patients have common spiritual and/or religious attitudes.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Adiponectin is encoded by the ADIPOQ gene and participates in the pathogenesis of cardiovascular and metabolic diseases. The goal of the study was to assess associations of rs17300539, rs266729, rs182052, rs2241766, and rs17366743 single nucleotide polymorphisms (SNPs) of the ADIPOQ gene with concentrations of serum adiponectin and with coronary atherosclerosis and type 2 diabetes mellitus in 447 patients (316 men and 131 women) subjected to coronary angiography. SNPs of the ADIPOQ gene of the study participants were genotyped using real-time PCR. Multivariate linear regression adjusted for covariates revealed significant association between rs182052 SNP and serum adiponectin concentration (β= –0.11; 95% confidence interval (95%CI): – 0.19, –0.03; p = 0.016). Regression analysis revealed an increase in prevalence of unstable angina (OR (odds ratio) = 2.55; 95%CI 1.4–4.82; p = 0.018) and coronary artery disease (OR = 1.55; 95%CI 1.15– 2.09; p = 0.021) per copy of the rs182052 A allele. Prevalence of type 2 diabetes mellitus was higher in subjects with the rs182052 A allele (OR = 2.29; 95%CI 1.29-4.21; p = 0.024). Regression analysis of rs266729 showed that prevalence of unstable angina was increased (OR = 3.59; 95%CI 1.17–10.01; p = 0.045) in the subjects with the GG genotype and prevalence of coronary artery disease (CAD) was significantly increased (OR = 1.48; 95%CI 1.09–2.03; p = 0.045) per copy of the G allele. Haplotype analysis revealed that the subjects with the GCATT haplotype have lower adiponectin levels (β= – 0.15; p = 0.042) and higher prevalence of unstable angina (OR = 3.597; p = 0.007) compared with reference haplotype carriers. Thus, the results indicate that minor A allele of rs182052 of the ADIPOQ gene is significantly associated with a decrease in serum adiponectin levels, and two SNPs (rs182052 and rs266729) of the ADIPOQ gene are significantly associated with cardiovascular and metabolic diseases.

© 2019 Elsevier B.V. Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellular‑calcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm2, 100 mW/cm2, 500 mW/cm2, 1000 mW/cm2, 1500 mW/cm2, 2000 mW/cm2) irradiated with a “standard” (Gaussian fluence distribution) hand-piece or with a “flat-top” (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.

© 2019 Elsevier GmbH We report a case of severe babesiosis caused by the bovine pathogen Babesia divergens with the development of multisystem failure in a splenic host. Immunosuppression other than splenectomy can also predispose people to B. divergens. There was heavy multiple invasion of up to 14 parasites inside the erythrocyte, which had not been previously observed even in asplenic hosts. The piroplasm 18S rRNA sequence from our patient was identical B. divergens EU lineage with identity 99.5–100%.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM.

© 2019 International Union of Crystallography. During a comprehensive study of a series of 2-(N-arylimino)coumarin-3-carboxamides with the aryl group substituted in the ortho-position by either a halogen atom, a methyl group or a methoxy group, the existence of three groups of isotypic crystal structures has been revealed. The similarity of crystal structures belonging to the same groups was confirmed by the analysis based on the comparison of pairwise interactions energies obtained from quantum chemical calculations. Group I includes unsubstituted, methyl-substituted and polymorphic modification 1 of fluoro-substituted 2-(N-arylimino)coumarin-3-carboxamide. Structures of polymorphic modification 2 of fluoro-substituted derivative, chloro-substituted and polymorphic modification 1 of bromo-substituted 2-(N-arylimino)coumarin-3-carboxamide may represent group II. Group III contains structures of polymorphic modification 2 of bromo-substituted derivative, iodine-and methoxy-substituted 2-(N-arylimino)coumarin-3-carboxamides. Structures of the same type group have extremely close parameters of the unit cell as well as those of molecular and crystal structures. But they are not identical. Polymorphic modifications of fluoro-and bromo-substituted 2-(N-arylimino)coumarin-3-carboxamides belong to different crystal types mainly due to different arrangement of basic structural motifs separated out using quantum chemical calculations.

Heart failure is a complex syndrome whose phenotypic presentation and disease progression depends on a complex network of adaptive and maladaptive responses. One of these responses is the endothelial release of NRG (neuregulin)-1-a paracrine growth factor activating ErbB2 (erythroblastic leukemia viral oncogene homolog B2), ErbB3, and ErbB4 receptor tyrosine kinases on various targets cells. NRG-1 features a multitasking profile tuning regenerative, inflammatory, fibrotic, and metabolic processes. Here, we review the activities of NRG-1 on different cell types and organs and their implication for heart failure progression and its comorbidities. Although, in general, effects of NRG-1 in heart failure are compensatory and beneficial, translation into therapies remains unaccomplished both because of the complexity of the underlying pathways and because of the challenges in the development of therapeutics (proteins, peptides, small molecules, and RNA-based therapies) for tyrosine kinase receptors. Here, we give an overview of the complexity to be faced and how it may be tackled.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Calcium ions (Ca2+) influx to mitochondrial matrix is crucial for the life of a cell. Mitochondrial calcium uniporter (mtCU) is a protein complex which consists of the pore-forming subunit (MCU) and several regulatory subunits. MtCU is the main contributor to inward Ca2+ currents through the inner mitochondrial membrane. Extensive investigations of mtCU involvement into normal and pathological molecular pathways started from the moment of discovery of its molecular components. A crucial role of mtCU in the control of these pathways is now recognized in both health and disease. In particular, impairments of mtCU function have been demonstrated for cardiovascular and skeletal muscle-associated pathologies. This review summarizes the current state of knowledge on mtCU structure, regulation, and function in different types of muscle tissues in health and disease.

© 2019 Elsevier Inc. Purpose: To identify preoperative risk factors for disease recurrence, following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), and to create a predictive nomogram. Materials and methods: Based on a multicenter database, we identified patients who underwent RNU due to high grade UTUC. Urothelial carcinoma of the bladder or contralateral UTUC was not considered as recurrence. Cox regression model was used to determine the effect of different preoperative variables as predictors of recurrence. Results: Two hundred and forty-five patients were included in the analysis. The 2 and 5 years recurrence rates were 16.3% and 19.2%, respectively. Factors associated with recurrence on univariable analysis were sessile architecture hazard ratio (HR) 3.16 (95% CI, 1.38–7.26, P = 0.006), ≥cT3 disease HR 2.30 (95% CI, 1.12–4.72, P= 0.023), age >65 HR 2.02 (95% CI, 1.00–4.05, P= 0.048), Eastern Cooperative Group > 0 HR 1.98 (95% CI, 1.09–3.57, P= 0.023), hydronephrosis HR 1.93 (95% CI, 1.04–3.57, P= 0.035). Higher hemoglobin levels HR 0.81 (95% CI, 0.69–0.96, P= 0.013) and preoperative estimated glomerular filtration rate ≥ 50 HR 0.48 (95% CI, 0.25–0.92, P = 0.028) were associated with lower probability for recurrence. Multivariable analysis identified sessile architecture as the only independent predictor of recurrence HR 2.52 (95% CI, 1.09–5.86, P= 0.0308). C-index of 0.71 was calculated for a predictive model including all variables in the multivariable analysis, indicating good predictive accuracy. A nomogram predicting 2 and 5 year recurrence free probability was developed accordingly. Conclusions: Based on a multicenter database, we developed a nomogram with good predictive accuracy for recurrence following RNU. This may serve as an aid in decision-making regarding the use of neoadjuvant chemotherapy.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Sterols change the biophysical properties of lipid membranes. Here, we analyzed how sterols affect the activity of widely used antimicrobial membrane-active compounds, sodium dodecyl sulfate (SDS) and benzalkonium chloride (BAC). We also tested a novel benzalkonium-like substance, Kor105. Our data suggest that benzalkonium and Kor105 disturb the ordering of the membrane lipid packaging, and this disturbance is dampened by cholesterol. The disturbance induced by Kor105 is stronger than that induced by BAC because of the higher rigidity of the Kor105 molecule due to a shorter linker between the phenyl group and quaternary nitrogen. On the contrary, individual SDS molecules do not cause the disturbance. Thus, in the tested range of concentrations, SDS-membrane interaction is not influenced by cholesterol. To study how sterols influence the biological effects of these chemicals, we used yeast strains lacking Lam1-4 proteins. These proteins transport sterols from the plasma membrane into the endoplasmic reticulum. We found that the mutants are resistant to BAC and Kor105 but hypersensitive to SDS. Together, our findings show that sterols influence the interaction of SDS versus benzalkonium chloride and Kor105 with the membranes in a completely different manner.

© 2019 by the authors. In today's analytical trends, there is an ever-increasing importance of polymeric materials for low molecular weight compounds including amines and drugs because they can act as carriers or capture amines or drugs. The use of this type of materials will allow the development of modern materials for the chromatographic column beds and the substrates of selective sensors. Moreover, these kinds of materials could be used as a drug carrier. Therefore, the aim of this study is presenting the synthesis and complexing properties of star-shaped oxiranes as a new sensor for the selective complexation of low molecular weight compounds. Propylene oxide and selected oxirane monomers with carbazolyl in the substituent were selected as the monomers in this case and tetrahydrofuran as its solvent. The obtained polymer structures were characterized using the MALDI-TOF. It was found that in the initiation step potassium hydride deprotonates the monomer molecule and takes also part in the nucleophilic substitution. The resulting polymeric material preferably cross-linked with selected di-oxiranes (1,2,7,8-diepoksyoktan in respect ratio 3:1 according to active center) was then used as a stationary phase in the column and thin layer chromatography for amine separation and identification. Sorption ability of the resulting deposits was determined using a quartz microbalance (QCMB). The study was carried out in stationary mode and flow cells to simulate actual operating phase conditions. Based on changes in electrode vibration frequency, the maximum amount of adsorbed analyte and the best conditions for its sorption were determined. 2019 by the authors.

© 2019 Elsevier Inc. In order to investigate the prevalence and prognostic value of the polymorphic variant (1245A>C) of the HSD3B1 gene, in the tumors of patients with castration-resistant prostate cancer, we retrospectively analyzed a small number of tumor samples from 44 patients by genomic sequencing. We noticed a relatively high prevalence in the overall study group (n = 23; 52.2%) as well as in the subgroup of patients undergoing second systemic treatment (n = 20; 51.2%) where we assessed for survival outcomes. However, this alteration was neither associated with the time to progression nor with survival.

© 2019 British Society for Neuroendocrinology The growth hormone secretagogue receptor (GHSR) is a G protein-coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver-expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin-evoked activity. GHSR also displays ligand-independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake-related behaviours, including binge eating. Previously, we reported that GHSR-deficient mice daily and time-limited exposed to a high-fat (HF) diet display an attenuated binge-like HF intake compared to wild-type mice. In the present study, we aimed to determine whether ligand-independent GHSR activity affects binge-like HF intake in a 4-day binge-like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge-like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K-(D-1-Nal)-FwLL-NH2, which are both blockers of constitutive GHSR activity, reduced binge-like HF intake, whereas central administration of ghrelin or the ghrelin-evoked GHSR activity blockers [D-Lys3]-GHRP-6 and JMV2959 did not modify binge-like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge-like HF intake in mice independently of plasma levels of ghrelin and LEAP2.

© 2019 Wolters Kluwer Health, Inc. Purpose of reviewThe current review summarizes contemporary decellularization and hydrogel manufacturing strategies in the field of tissue engineering and regenerative medicine.Recent findingsDecellularized extracellular matrix (ECM) bioscaffolds are a valuable biomaterial that can be purposed into various forms of synthetic tissues such as hydrogels. ECM-based hydrogels can be of animal or human origin. The use of human tissues as a source for ECM hydrogels in the clinical setting is still in its infancy and current literature is scant and anecdotal, resulting in inconclusive results.SummaryThus far the methods used to obtain hydrogels from human tissues remains a work in progress. Gelation, the most complex technique in obtaining hydrogels, is challenging due to remarkable heterogeneity of the tissues secondary to interindividual variability. Age, sex, ethnicity, and preexisting conditions are factors that dramatically undermine the technical feasibility of the gelation process. This is contrasted with animals whose well defined anatomical and histological characteristics have been selectively bred for the goal of manufacturing hydrogels.

© 2019 The Authors International Journal for Numerical Methods in Biomedical Engineering Published by John Wiley  &  Sons Ltd Non-invasive coronary computed tomography (CT) angiography-derived fractional flow reserve (cFFR) is an emergent approach to determine the functional relevance of obstructive coronary lesions. Its feasibility and diagnostic performance has been reported in several studies. It is unclear if differences in sensitivity and specificity between these studies are due to study design, population, or "computational methodology." We evaluate the diagnostic performance of four different computational workflows for the prediction of cFFR using a limited data set of 10 patients, three based on reduced-order modelling and one based on a 3D rigid-wall model. The results for three of these methodologies yield similar accuracy of 6.5% to 10.5% mean absolute difference between computed and measured FFR. The main aspects of modelling which affected cFFR estimation were choice of inlet and outlet boundary conditions and estimation of flow distribution in the coronary network. One of the reduced-order models showed the lowest overall deviation from the clinical FFR measurements, indicating that reduced-order models are capable of a similar level of accuracy to a 3D model. In addition, this reduced-order model did not include a lumped pressure-drop model for a stenosis, which implies that the additional effort of isolating a stenosis and inserting a pressure-drop element in the spatial mesh may not be required for FFR estimation. The present benchmark study is the first of this kind, in which we attempt to homogenize the data required to compute FFR using mathematical models. The clinical data utilised in the cFFR workflows are made publicly available online.

© 2019 Elsevier Inc. Objectives: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC. Materials and method: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis. Results: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology. Conclusions: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.