Canadian Studies: Society, Culture, Language

У міжнародній колективній монографії вміщено найновіші українсько-канадські суспільно-політичні, культурно-освітні та філологічні дослідження в галузі сучасного канадознавства. Це другий випуск серії «Канадознавство», заснованої у 2018 р. Центром канадознавства Східноєвропейського національного університету імені Лесі Українки (м. Луцьк). Для науковців, викладачів, докторантів, аспірантів, студентів факультетів міжнародних відносин, іноземної філології, історії, політології та національної безпеки, філології й журналістики, педагогічної освіти й соціальної роботи, для працівників осередків канадознавста в Україні, авторів українських студій у Канаді, а також усіх, хто цікавиться канадознавством, українсько-канадською співпрацею в різних сферах.Монографія видається за підтримки Центру українських канадських студій Манітобського університету (м. Вінніпег, Канада

Dual roles of the adenosine A2a receptor in autoimmune neuroinflammation

BackgroundConditions of inflammatory tissue distress are associated with high extracellular levels of adenosine, due to increased adenosine triphosphate (ATP) degradation upon cellular stress or the release of extracellular ATP upon cell death, which can be degraded to adenosine by membrane-bound ecto-enzymes like CD39 and CD73. Adenosine is recognised to mediate anti-inflammatory effects via the adenosine A2a receptor (A2aR), as shown in experimental models of arthritis. Here, using pharmacological interventions and genetic inactivation, we investigated the roles of A2aR in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).MethodsWe used two independent mouse EAE variants, i.e. active immunization in C57BL/6 with myelin oligodendrocyte glycoprotein (MOG)35-55 or transfer-EAE by proteolipid protein (PLP)139-155-stimulated T lymphocytes and EAE in mice treated with A2aR-agonist CGS21680 at different stages of disease course and in mice lacking A2aR (A2aR−/−) compared to direct wild-type littermates. In EAE, we analysed myelin-specific proliferation and cytokine synthesis ex vivo, as well as inflammation and demyelination by immunohistochemistry. In vitro, we investigated the effect of A2aR on migration of CD4+ T cells, macrophages and microglia, as well as the impact of A2aR on phagocytosis of macrophages and microglia. Statistical tests were Mann-Whitney U and Student’s t test.ResultsWe found an upregulation of A2aR in the central nervous system (CNS) in EAE, predominantly detected on T cells and macrophages/microglia within the inflamed tissue. Preventive EAE treatment with A2aR-specific agonist inhibited myelin-specific T cell proliferation ex vivo and ameliorated disease, while application of the same agonist after disease onset exacerbated non-remitting EAE progression and resulted in more severe tissue destruction. Accordingly, A2aR-deficient mice showed accelerated and exacerbated disease manifestation with increased frequencies of IFN-γ-, IL-17- and GM-CSF-producing CD4+ T helper cells and higher numbers of inflammatory lesions in the early stage. However, EAE quickly ameliorated and myelin debris accumulation was lower in A2aR−/− mice. In vitro, activation of A2aR inhibited phagocytosis of myelin by macrophages and primary microglia as well as migration of CD4+ T cells, macrophages and primary microglia.ConclusionsA2aR activation exerts a complex pattern in chronic autoimmune neurodegeneration: while providing anti-inflammatory effects on T cells and thus protection at early stages, A2aR seems to play a detrimental role during later stages of disease and may thus contribute to sustained tissue damage within the inflamed CNS

Biochemical changes in Oenothera biennis plants infected by 'Candidatus Phytoplasma solani'

The aim of the present paper was to study the response of Oenothera biennis L. to 'Candidatus Phytoplasma solani' (Stolbur) infection by analyzing total sugars, polyphenols, photosynthetic pigments content and the antioxidant capacity in leaves and roots of healthy and infected plants. The infection caused a significant increase in peroxidation of lipids, phenylalanine ammonia-lyase activity, total sugar, polyphenols and anthocyanins content (2.8, 2.6, 1.8, 1.4, 6.8 fold, respectively), as well as a decrease in photosynthetic pigments (2-6 fold) and total flavonoids (1.5 fold) in the leaves of Oe. biennis. Changes in these parameters were insignificant in the roots except for the total polyphenols content that was 2.7 times higher in the infected ones. Reduced gluthatione content in both tested organs was not affected by the infection (3.7 and 1.7 mu mol/g fresh weight of leaves and roots, respectively). The elevated content of total sugars, flavonoids and polyphenols, as well as the reduction of photosynthetic pigments and anthocyanins in infected plants are indicative of changes in the metabolism of Oe. biennis affected by the Stolbur phytoplasma. In addition to reduction of chlorophyll and carotenoids, the phytoplasma accelerated leaf senescence. Plants responded to the infection via enhanced superoxide anion scavenging, even though this reaction did not prevent, apparently, membrane damage in analysed leaves. This investigation presents new data on the effect of a phytoplasma infection on its host

Subspecialty training in Europe: A report by the European Network of Young Gynaecological Oncologists

Background ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. Methodology National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. Results National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. Conclusion Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training. © 2021 BMJ Publishing Group. All rights reserved

Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis

Chronic disability in multiple sclerosis is linked to neuroaxonal degeneration. 4-aminopyridine (4-AP) is used and licensed as a symptomatic treatment to ameliorate ambulatory disability in multiple sclerosis. The presumed mode of action is via blockade of axonal voltage gated potassium channels, thereby enhancing conduction in demyelinated axons. In this study, we provide evidence that in addition to those symptomatic effects, 4-AP can prevent neuroaxonal loss in the CNS. Using in vivo optical coherence tomography imaging, visual function testing and histologic assessment, we observed a reduction in retinal neurodegeneration with 4-AP in models of experimental optic neuritis and optic nerve crush. These effects were not related to an anti-inflammatory mode of action or a direct impact on retinal ganglion cells. Rather, histology and in vitro experiments indicated 4-AP stabilization of myelin and oligodendrocyte precursor cells associated with increased nuclear translocation of the nuclear factor of activated T cells. In experimental optic neuritis, 4-AP potentiated the effects of immunomodulatory treatment with fingolimod. As extended release 4-AP is already licensed for symptomatic multiple sclerosis treatment, we performed a retrospective, multicentre optical coherence tomography study to longitudinally compare retinal neurodegeneration between 52 patients on continuous 4-AP therapy and 51 matched controls. In line with the experimental data, during concurrent 4-AP therapy, degeneration of the macular retinal nerve fibre layer was reduced over 2 years. These results indicate disease-modifying effects of 4-AP beyond symptomatic therapy and provide support for the design of a prospective clinical study using visual function and retinal structure as outcome parameters