Репозиторий Университета

Background: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. Methods: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. Results: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. Conclusions: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Due to the cost efficiency and environmentally friendly surfactant features in enhanced oil recovery techniques, the appropriate designation of surfactant flooding should be considered. It is essential to evaluate the crucial factors that affect surfactant adsorption on rock surfaces to eliminate the total economic losses of surfactant retention and adsorption in porous media. In this paper, the considerable influence of temperature, different surfactant concentrations, and polymer addition were experimentally investigated for dolomite minerals extracted from Pabdeh formation. According to this study, higher adsorption density has occurred at lower temperatures, which implies lower kinetic energy between the surfactant molecules. For 25 ℃, the adsorption density is about 41 mg/g, and it has the lowest value of 100 ℃. It is about 17 mg/g. By the increase of surfactant concentration for different time steps, adsorption density has been increased. For the surfactant concentration of 5 Wt. %, the adsorption density is about 42 mg/g; however, it is for 0.15 Wt. % of surfactant concentration, the adsorption density is about 1 mg/g. Moreover, due to the higher stability of polymers, adsorption density has been decreased by the addition of polymer. The stopping time for each surfactant concentration is about 6.5 h for the surfactant concentration of 5 Wt. %. Consequently, the critical micelle concentration point is about 3.5 Wt. %, 4 Wt. %, and 5 Wt. % for linear alkylbenzene sulfonic acid, cetyl trimethyl ammonium bromide, and Triton X-100, respectively. This change in the conductivity is related to the start of the micelling process by increasing surfactant concentration.

A correlation between the crystal structure and magnetic properties of system (1-x)BiFeO3 – (x)BaTiO3 with compounds across the morphotropic phase boundary was studied using X-ray and neutron diffraction, magnetometry, and Mössbauer spectroscopy measurements. Increase in the dopants content leads to the structural transition from the rhombohedral phase to the cubic phase via a formation of the two-phase region (0.2 < x < 0.33), wherein the magnetic structure changes from the modulated G-type antiferromagnetic to the collinear antiferromagnetic via a stabilization of the non-collinear antiferromagnetic phase with non-zero remanent magnetization. The value of magnetic moment calculated per iron ion based on the Mössbauer and neutron diffraction data decreases from m ≈ 4.4 μB for the compound with x = 0.25 to m = 3.2 μB for the compound with x = 0.35 testifying a dominance of 3 + oxidation state of the iron ions. Increase in the amount of the cubic phase leads to a reduction in the remanent magnetization from 0.02 emu/g for the compounds with the dominant rhombohedral phase (x < 0.27) down to about 0.001 emu/g for the compounds with dominant cubic structure (x ≥ 0.27). Rapid decrease in the remanent magnetization observed in the compounds across the phase coexistence region points at no direct correlation between the type of structural distortion and non-zero remanent magnetization, while the oxygen octahedra tilting is the key factor determining the presence of non-zero remanent magnetization.

© 2021 Elsevier GmbH The expanding phylogenetic tree of trypanosomatid flagellates (Kinetoplastea: Trypanosomatidae) contains a long-known and phylogenetically well-supported species-rich lineage that was provisionally named as the ‘jaculum’ clade. Its members were found in representatives of several unrelated families of heteropteran bugs captured in South and Central America, Europe, Africa, and Asia. However, this group resisted introduction into the culture, a needed prerequisite for its proper characterization. Here we describe four new cultivable species, which parasitize various parts of their hosts’ intestine, including the thoracic and abdominal part of the midgut, hindgut, and Malpighian tubules. Morphologically, the cultured flagellates vary from relatively short stumpy promastigotes to long slender leptomonad cells. Some species form straphangers (cyst-like amastigotes) both in vivo and in vitro, initially attached to the basal part of the flagellum of the mother cell, from which they subsequently detach. To formally classify this enigmatic monophyletic cosmopolitan clade, we erected Obscuromonas gen. nov., including five species: O. modryi sp. nov. (isolated from the true bug host species Riptortus linearis captured in the Philippines), O. volfi sp. nov. (from Catorhintha selector, Curaçao), O. eliasi sp. nov. (from Graptostethus servus, Papua New Guinea), O. oborniki sp. nov. (from Aspilocoryphus unimaculatus, Madagascar), and O. jaculum comb. nov. (from Nepa cinerea, France). Obscuromonas along with the genus Blastocrithidia belongs to the newly established Blastocrithidiinae subfam. nov.

© 2021 Elsevier Ltd This review examines investigations into the functionalization of polysaccharides by substituents containing multiple (C[dbnd]C) bonds and thiol (SH) groups that are prone to (co)polymerization in the presence of thermal, redox and photoinitiators or Michael addition reactions. A comparative analysis of the approaches to grafting the mentioned substituents onto the polysaccharide macromolecules was conducted. The use of the modified polysaccharides for the design of the 3D structures, including for the development of the pore bearing matrixes of cells or scaffolds utilized in regenerative medicine was examined. These modified polymers were also examined toward the design of excipient matrixes in pharmacological compositions, including with controllable release of active pharmaceuticals, as wel as of antibacterial and antifungal agents and others. In addition, a few examples of the use of modified derivatives in other areas are given.

© 2021 Introduction: Synthetic cannabinoids are abused substances with strong psychoactive effects. Little is known about the effects on neurotransmission and the toxicity of the second-generation cannabinoid 5F-APINAC. The objective was to assess the influence of short- and long-term exposures of 5F-APINAC on metabolites associated with neurotransmission on zebrafish. Methods: Short-term (“acute”, 4 h) and long-term (“chronic”, 96 h) exposures to 5F-APINAC were performed at 0.001, 0.01, 0.1, 1.0 and 10 μM. Intervention groups were compared with a vehicle control. Each group n = 20 zebrafish eggs/larvae. Metabolites related to neurotransmission were determined. Results: In chronic exposure, larvae exposed to 10 μM 5F-APINAC presented morphological and developmental alterations. GABA had the lowest concentrations at higher exposure in acute (p < 0.01) and chronic (p < 0.001) experiments. Glutamine showed a descending trend in the acute experiment, but an ascending trend in the chronic exposure (p < 0.05). In chronic exposure, tryptophan presented an overall descending trend, but with a neat increase at 10 μM 5F-APINAC (p < 0.001). Tryptamine in acute exposure presented lower (p < 0.05) concentrations at higher doses. Dopamine and acetylcholine presented highest (p < 0.05) concentrations in the acute and chronic exposures, but with a drop at the highest doses in the chronic experiments. In chronic exposure, xanthurenic acid decreased, except for the highest dose. Picolinic acid was increased at the highest doses in the chronic experiment (p < 0.001). Conclusions: Short- and long-term exposures induced metabolomic alterations associated with the gamma-aminobutyric acid/glutamic acid, dopaminergic/adrenergic, cholinergic neurotransmitter systems, and the kynurenine pathway. Chronic exposure at 10 μM 5F-APINAC was associated with embryotoxicity confirmed by teratogenesis.

© 2021 Elsevier B.V. Innovative Mn-containing glass ceramic (Na2O[2.00]-K2O[0.09]-MgO[3.10]-MnO[2.07]-CaO[38.78]-CaF2[2.25]-P2O5[9.66]-SiO2[41.71] [wt%]) was obtained by sol-gel. It was investigated by High Resolution Field Emission Scanning Electron Microscopy, Energy Dispersive X-Ray Spectroscopy, X-Ray fluorescence, X-Ray Diffraction, and Fourier Transform Infrared Spectroscopy. Ion release characteristics of the glass ceramic powder were quantified via Inductively Coupled Plasma Optical Emission Spectroscopy. Biological tests were performed using equine adipose tissue mesenchymal stem cells (AMSCs). MTT assay demonstrated the cytocompatibility of the prepared material. AMSCs differentiation test showed that the glass ceramic favored the stem cell differentiation in adipogenic, chondrogenic, and osteogenic lineages, the last one being qualitatively more pronounced. The antimicrobial properties were evaluated against Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Salmonella typhi, and Staphylococcus aureus bacteria strains and Candida albicans fungus. The inhibition of Gram-negative bacteria (S. tiphy, E. coli), Gram-positive (E. faecalis) and fungus (C. albicans) was detected, while the inhibition of P. aeruginosa and S. aureus was not significant.

© 2020 by the authors. The success of using soft tissue transplants is enough for their spreading in the clinic, but the need to cover the surface, where the transplant was taken from, can be forgotten. It can lead to long-term discomfort of the patient in real life, in some cases to complications alike bleeding; We performed the analysis of the use of different new xenogenic resorbable membranes created within our University in compare with the natural healing of oral mucosa defects in the experiment in vivo on 36 rabbits after performing of the surgical wound on the palatine side (5x5 mm). All animals were separated (divided) for 3 groups: #1 group of control and main groups #2 and #3, where we used pericardium and collagen film for covering mucous defects. We assessed the edema, hyperemia in the operation side, the pain according to animal behavior, the histological picture after animals completion of the experiment (on 3rd, 6th and 10th days); The decrease of clinical signs of inflammation in groups of collagen and pericardium films use (p<0.05) was statistically confirmed. Analysis of histologic investigation of biopsy specimens has shown the faster and massive growth of soft tissue in the donor site after application of pericardium and collagen films (p<0.05). An analysis of the experiment results allows recommending their possible use for closing the donor site after taking a free gingival graft or in the zone of postoperative wound defect in the oral mucosa in clinical oral surgery after specific clinical trials.

© 2021 Elsevier Ltd The functionalization of the bacterial cellulose (BC) surface with a chitosan biopolymer to expand the areas of possible applications of the modified BC is an important scientific task. The creation of such composites in the carbonic acid solutions that were performed in this work has several advantages in terms of being biocompatible and eco-friendly. Quantitative analysis of chitosan content in the composite was conducted by tritium-labeled chitosan radioactivity detection method and this showed three times increased chitosan loading. Different physicochemical methods showed successful incorporation of chitosan into the BC matrix and interaction with it through hydrogen bonds. Microscopy results showed that the chitosan coating with a thickness of around 10 nm was formed in the bulk of BC, covering each microfibril. It was found that the inner specific surface area increased 1.5 times on deposition of chitosan from the solutions in carbonic acid.

© 2021 Elsevier B.V. Based on a comprehensive theoretical and experimental approach, a low-defect thin film of stable dimeric phthalocyanine zinc complex (bis-[2-hydroxy-9(10),16(17), 23(24)-tri-tert-butylphthalocyanine]zinc – J-[OHPctZn]2) was prepared. It is shown that the dye forms stable amorphous edge-on monolayers at the air/water interface with an insignificant content of cylindrical 3D aggregates. These floating layers keep their structure when transferred by the Langmuir-Schaefer method onto a solid substrate, demonstrating a tendency towards ordered H-aggregation with preserving their linear molecular properties. Mixed two- and three-photon absorption of femtosecond laser pulses (280 fs) was firstly detected on this sample, as well as the ability of a material to the nonlinear attenuation of the intense irradiation, which is important for optical limiting.

© 2020, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature. One dimensional (1D) nanostructures attract considerable attention, enabling a broad application owing to their unique properties. However, the precise mechanism of 1D morphology attainment remains a matter of debate. In this study, ultrafast picosecond (ps) laser-induced treatment on upconversion nanoparticles (UCNPs) is offered as a tool for 1D-nanostructures formation. Fragmentation, reshaping through recrystallization process and bioadaptation of initially hydrophobic (β-Na1.5Y1.5F6: Yb3+, Tm3+/β-Na1.5Y1.5F6) core/shell nanoparticles by means of one-step laser treatment in water are demonstrated. “True” 1D nanostructures through “Medusa”-like structures can be obtained, maintaining anti-Stokes luminescence functionalities. A matter of the one-dimensional UCNPs based on direction of energy migration processes is debated. The proposed laser treatment approach is suitable for fast UCNP surface modification and nano-to-nano transformation, that open unique opportunities to expand UCNP applications in industry and biomedicine. [Figure not available: see fulltext.].

© 2021 The aim of this work was to compare mesoporous carriers based on silica and magnesium aluminosilicate in the amorphous solid dispersion production. Darunavir has been selected as an active pharmaceutical ingredient that is classified as a Class 2 BCS substance and exists in two commercially available forms: crystalline ethanolate and amorphous. In the course of the study, the conditions for the preparation of amorphous samples with the selected carriers were evaluated within the framework of the most common methods for obtaining solid dispersions - hot-melt extrusion, solvent wetting, and spray drying. It was determined that the obtained dispersion properties almost completely repeat the properties of the corresponding carriers. The resulting dispersions were examined in a dissolution test and the best ones was used to formulate tablets, which were studied in an in vitro dissolution test with the original Prezista. The proposed tablet formulation showed improved dissolution compared to the original one. It was also found that silica supports have a greater positive contribution to darunavir dissolution - both ethanolate or amorphous forms.

© 2020 Elsevier Inc. Information Centric Networking (ICN) provides caching strategies to improve network performance based on consumer demands from the intermediate routers. It reduces the load on content server, network traffic, and improves end-to-end delay. The content requesters use an Interest packet containing the name of data to express their needs. If such Interest packets are routed efficiently, the end to end delay and throughput of the network could be improved further. This paper describes an efficient method of forwarding Interest packets to retrieve the requested content at the earliest possible time. Here the data source is found and considered as a single player game with content requester as its start state and location of the desired content as final or goal state. The Monte Carlo Tree Search (MCTS) algorithm is used for constructing the path from content requester to concerned data source. For performance evaluation, the proposed scheme is integrated with Leave Copy Down (LCD) and Leave Copy Everywhere (LCE), Cache Less for More (CL4M), and Probability based caching (ProbCache) In ns-3 simulation environment (ndnSim), all these are evaluated in terms of content search latency, server hit ratio, network load, overhead and throughput. Simulation observation reveals that the integration of MCTS significantly improves performance in regard to experimental parameters.

© 2020 This study demonstrates an ultra-sensitive material towards 1-butylamine. The material is composed of 4 wt% Au nanoparticles decorated on MoO3 nanobelts, which are prepared via the hydrothermal method and in-situ reduction. The related characterizations reveal that the nanobelts are highly crystallized layer structures with a width of ~ 200 nm, a thickness of 40 nm and a length of several micrometers. The Au/MoO3 composites exhibit ultra-high sensing response (~300) towards 100 ppm of 1-butylamine at the working temperature of 240 °C. Even without Au decoration, the pristine MoO3 nanobelts offer the response as high as ~ 90 toward the same concentration of 1-butylamine at the temperature of 340 °C, much higher than the existing materials. More importantly, the proposal materials have excellent selectivity towards 1-butylamine, which offers the possibility for practical use. The excellent sensing performance is attributed to the unique sensing mechanism of the layered MoO3 nanobelts via catalytic reaction between 1-butylamine and the lattice oxygen of MoO3. Besides, Au decoration enables to enhance the adsorption of 1-butylamine and facilitate the catalytic sensing process, resulting in further increase in sensing response and selectivity of 1-butylamine. This study may shield light on a promising high-performance gas sensing materials to detect amines in practical application.

© 2020 Elsevier Ltd A laser technology has been developed for fabricating structures from composite layers based on biopolymers: albumin, collagen, and chitosan with single-walled carbon nanotubes (SWCNT). The structures are intended for cardiovascular devices and tissue-engineered implants. This is evidenced by the results of studies. The composite layers were fabricated due to the phase transition of biopolymers and SWCNT aqueous dispersion under the influence of laser pulses. At the same time branched 3D networks of SWCNT were formed in the biopolymer matrix. The threshold energy fluence of laser pulses was determined (0.032–0.083 J/cm2) at which a bimodal distribution of pores was observed. The calculation of contact resistances between nanotubes at percolation units of 3D networks (20–100 kOhm) was carried out. Composite layers fabricated by laser demonstrated conductivity values that were higher (12.4 S/m) than those for layers by thermostat (4.7 S/m). The maximum hardness of the composite layers with SWCNT (0.01 wt%) by laser was 482 ± 10, 425 ± 10, and 407 ± 15 MPa for albumin, collagen and chitosan, respectively. The hardness of the thermostat layers was less than 100 MPa. The viability of endothelial cells in composite layers was improved. The composite layers ensured a normal level of hemolysis during interaction with erythrocytes.

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2020 Elsevier Ltd Objectives: To test contemporary rates and predictors of open conversion at minimally invasive partial nephrectomy (MIPN: laparoscopic or robotic partial nephrectomy). Materials and methods: Within the National Inpatient Sample database (2008–2015) we identified all MIPN patients and patients that underwent open conversion at MIPN. First, estimated annual percentage changes (EAPC) tested temporal trends of open conversion. Second, univariable and multivariable logistic regression models predicted open conversion at MIPN. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. Results: Of 7649 MIPN patients, 287 (3.8%) underwent open conversion. The rates of open conversion decreased over time (from 12 to 2.4%; EAPC: 24.8%; p = 0.004). In multivariable logistic regression models predicting open conversion, patient obesity achieved independent predictor status (OR:1.80; p < 0.001). Moreover, compared to high volume hospitals, medium volume (OR:1.48; p = 0.02) and low volume hospitals (OR:2.11; p < 0.001) were associated with higher rates of open conversion. Last but not least, when the effect of obesity was tested according to hospital volume, the rates of open conversion ranged from 2.2 (non obese patients treated at high volume hospitals) to 9.8% (obese patients treated at low volume hospitals). Conclusion: Overall contemporary (2008–2015) rate of open conversion at MIPN was 3.8% and it was strongly associated with patient obesity and hospital surgical volume. In consequence, these two parameters should be taken into account during preoperative patients counselling, as well as in clinical and administrative decision making.

© 2020 Objective: The association between the most severe types of placenta accreta spectrum disorders and caesarean scar pregnancy (CSP) poses the question of whether early diagnosis may impact the clinical outcome of these anomalies. The aim of this study is to report the outcome of cesarean scar pregnancy (CSP) diagnosed in the early (≤9 weeks) versus late (>9 weeks) first trimester of pregnancy. Study design: Medline, Embase and Clinicaltrail.gov databases were searched. Studies including cases of CSP with an early (≤9 weeks of gestation) compared to a late (>9 weeks) first trimester diagnosis of CSP, followed by immediate treatment, were included in this systematic review. The primary outcome was a composite measure of severe maternal morbidity including either severe first trimester bleeding, need for blood transfusion, uterine rupture or emergency hysterectomy. The secondary outcomes were the individual components of the primary outcome. Random-effect meta-analyses were used to combine data. Results: Thirty-six studies (724 women with CSP) were included. Overall, composite adverse outcome complicated 5.9 % (95 % CI 3.5−9.0) of CSP diagnosed ≤9 weeks and 32.4 % (95 % CI 15.7−51.8) of those diagnosed >9 weeks. Massive hemorrhage occurred in 4.3 % (95 % CI 2.3−7.0) of women with early and in 28.0 % (95 % CI 14.1−44.5) of those with late first trimester diagnosis of CSP, while the corresponding figures for the need for blood transfusion were 1.5 % (95 % CI 0.6−2.8) and 15.8 % (95 % CI 5.5−30.2) respectively. Uterine rupture occurred in 2.5 % (95 % CI 1.2−4.1) of women with a prenatal diagnosis of CSP ≤ 9 weeks and in 7.5 % (95 % CI 2.5−14.9) of those with CSP > 9 weeks, while an emergency intervention involving hysterectomy was required in 3.7 % (95 % CI 2.2−5.4) and 16.3 % (95 % CI5.9−30.6) respectively. When computing the risk, early diagnosis of CSP was associated with a significantly lower risk of composite adverse outcome, (OR: 0.14; 95 % CI 0.1−0.4 p < 0.001). Conclusions: Early first trimester diagnosis of CSP is associated with a significantly lower risk of maternal complications, thus supporting a policy of universal screening for these anomalies in women with a prior cesarean delivery although the cost-effectiveness of such policy should be tested in future studies.