АНАЛІЗ БАЗОВИХ УМОВ ЗДІЙСНЕННЯ РЕФОРМИ ДЕЦЕНТРАЛІЗАЦІЇ В УКРАЇНІ ТА ПОЛЬЩІ

The article examines the current state of implementation of the decentralization reform in Ukraine, which highlights the issues of the formation of the chosen European integration vector of development, the fundamental basis of which was the need to implement the decentralization reform of the administrative and territorial system of Ukraine and the institution of local self - government. By choosing foreign experience in conducting such a reform, the experience of Poland became a model. An analysis of the Polish form of decentralization and the election of Ukraine of a definite decentralization model is underway. The comparison of the main parameters of the economic development of Ukraine and Poland in the beginning of individual stages of the decentralization reform, which is taken as the main indicator of the dynamics of GDP, inflation.The main factors that influence the process of decentralization, in particular the Ukrainian economy as a whole, are determined. Separate problems that the reformers face in the process of decentralization of the administrative - territorial system of Ukraine.The prospects for developing the expediency of choosing a Polish decentralization experience for implementation in domestic conditions have been formed.Исследуются базовые условия осуществления реформы децентрализации в Украине на примере Польши. Проводится анализ польской формы децентрализации и избрание Украины определенной модели децентрализации. Проведено сравнение основных параметров развития экономики Украины и Польши в начале отдельных этапов реформы децентрализации, где взято за основной показатель динамики объема ВВП. Сформированы перспективы развития целесообразности избрания польского опыта децентрализации для внедрения в современных условиях.Досліджується сучасний стан здійснення реформи децентралізації в Україні, де висвітлюються питання становлення обраного євроінтеграційного вектору розвитку, фундаментальною основою якого стала необхідність здійснення реформи децентралізації адміністративно-територіального устрою України та інституту місцевого самоврядування. При обранні зарубіжного досвіду проведення подібної реформи взірцем став досвід Польщі. Проводиться аналіз польської форми децентралізації та обрання Україною визначеної моделі децентралізації. Здійснено порівняння основних параметрів розвитку економіки України і Польщі на початку окремих етапів реформи децентралізації, де взято за основний показник динаміки обсягу ВВП, інфляції.Визначено основні фактори, які впливають на процес децентралізації, зокрема і на економіку України загалом. Відокремлено проблеми, з якими зіштовхуються реформатори у процесі децентралізації адміністративно-територіального устрою України.Сформовано перспективи розвитку доцільності обрання польського досвіду децентралізації для впровадження у вітчизняних умовах

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites <i>Trypanosoma brucei</i> (<i>T.b.</i>) <i>gambiense</i> or <i>T.b.rhodesiense</i> and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage <i>T.b.rhodesiense</i> infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-͎-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties <i>in vitro</i> and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

Splint: the efficacy of orthotic management in rest to prevent equinus in children with cerebral palsy, a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Range of motion deficits of the lower extremity occur in about the half of the children with spastic cerebral palsy (CP). Over time, these impairments can cause joint deformities and deviations in the children's gait pattern, leading to limitations in moblity. Preventing a loss of range of motion is important in order to reduce secondary activity limitations and joint deformities. Sustained muscle stretch, imposed by orthotic management in rest, might be an effective method of preventing a decrease in range of motion. However, no controlled study has been performed.</p> <p>Methods</p> <p>A single blind randomised controlled trial will be performed in 66 children with spastic CP, divided over three groups with each 22 participants. Two groups will be treated for 1 year with orthoses to prevent a decrease in range of motion in the ankle (either with static or dynamic knee-ankle-foot-orthoses) and a third group will be included as a control group and will receive usual care (physical therapy, manual stretching). Measurements will be performed at baseline and at 3, 6, 9 and 12 months after treatment allocation. The primary outcome measure will be ankle dorsiflexion at full knee extension, measured with a custom designed hand held dynamometer. Secondary outcome measures will be i) ankle and knee flexion during gait and ii) gross motor function. Furthermore, to gain more insight in the working mechanism of the orthotic management in rest, morphological parameters like achilles tendon length, muscle belly length, muscle fascicle length, muscle physiological cross sectional area length and fascicle pennation angle will be measured in a subgroup of 18 participants using a 3D imaging technique.</p> <p>Discussion</p> <p>This randomised controlled trial will provide more insight into the efficacy of orthotic management in rest and the working mechanisms behind this treatment. The results of this study could lead to improved treatments.</p> <p>Trial Registration Number</p> <p>Nederlands Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2091">NTR2091</a></p

Eye Development under the control of SRp55/B52-Mediated Alternative Splicing of eyeless

The genetic programs specifying eye development are highly conserved during evolution and involve the vertebrate Pax-6 gene and its Drosophila melanogaster homolog eyeless (ey). Here we report that the SR protein B52/SRp55 controls a novel developmentally regulated splicing event of eyeless that is crucial for eye growth and specification in Drosophila. B52/SRp55 generates two isoforms of eyeless differing by an alternative exon encoding a 60-amino-acid insert at the beginning of the paired domain. The long isoform has impaired ability to trigger formation of ectopic eyes and to bind efficiently Eyeless target DNA sequences in vitro. When over-produced in the eye imaginal disc, this isoform induces a small eye phenotype, whereas the isoform lacking the alternative exon triggers eye over-growth and strong disorganization. Our results suggest that B52/SRp55 splicing activity is used during normal eye development to control eye organogenesis and size through regulation of eyeless alternative splicing

Molecular and physiological basis of Saccharomyces cerevisiae tolerance to adverse lignocellulose-based process conditions

Lignocellulose-based biorefineries have been gaining increasing attention to substitute current petroleum-based refineries. Biomass processing requires a pretreatment step to break lignocellulosic biomass recalcitrant structure, which results in the release of a broad range of microbial inhibitors, mainly weak acids, furans, and phenolic compounds. Saccharomyces cerevisiae is the most commonly used organism for ethanol production; however, it can be severely distressed by these lignocellulose-derived inhibitors, in addition to other challenging conditions, such as pentose sugar utilization and the high temperatures required for an efficient simultaneous saccharification and fermentation step. Therefore, a better understanding of the yeast response and adaptation towards the presence of these multiple stresses is of crucial importance to design strategies to improve yeast robustness and bioconversion capacity from lignocellulosic biomass. This review includes an overview of the main inhibitors derived from diverse raw material resultants from different biomass pretreatments, and describes the main mechanisms of yeast response to their presence, as well as to the presence of stresses imposed by xylose utilization and high-temperature conditions, with a special emphasis on the synergistic effect of multiple inhibitors/stressors. Furthermore, successful cases of tolerance improvement of S. cerevisiae are highlighted, in particular those associated with other process-related physiologically relevant conditions. Decoding the overall yeast response mechanisms will pave the way for the integrated development of sustainable yeast cell--based biorefineries.This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the strategic funding of UID/BIO/04469/2013 unit, MIT Portugal Program (Ph.D. grant PD/BD/128247/ 2016 to Joana T. Cunha), Ph.D. grant SFRH/BD/130739/2017 to Carlos E. Costa, COMPETE 2020 (POCI-01-0145-FEDER-006684), BioTecNorte operation (NORTE-01-0145-FEDER-000004), YeasTempTation (ERA-IB-2-6/0001/2014), and MultiBiorefinery project (POCI-01-0145-FEDER-016403). Funding by the Institute for Bioengineering and Biosciences (IBB) from FCT (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (Project N. 007317) was also receiveinfo:eu-repo/semantics/publishedVersio

АНАЛІЗ БАЗОВИХ УМОВ ЗДІЙСНЕННЯ РЕФОРМИ ДЕЦЕНТРАЛІЗАЦІЇ В УКРАЇНІ ТА ПОЛЬЩІ

The article examines the current state of implementation of the decentralization reform in Ukraine, which highlights the issues of the formation of the chosen European integration vector of development, the fundamental basis of which was the need to implement the decentralization reform of the administrative and territorial system of Ukraine and the institution of local self - government. By choosing foreign experience in conducting such a reform, the experience of Poland became a model. An analysis of the Polish form of decentralization and the election of Ukraine of a definite decentralization model is underway. The comparison of the main parameters of the economic development of Ukraine and Poland in the beginning of individual stages of the decentralization reform, which is taken as the main indicator of the dynamics of GDP, inflation.The main factors that influence the process of decentralization, in particular the Ukrainian economy as a whole, are determined. Separate problems that the reformers face in the process of decentralization of the administrative - territorial system of Ukraine.The prospects for developing the expediency of choosing a Polish decentralization experience for implementation in domestic conditions have been formed.Исследуются базовые условия осуществления реформы децентрализации в Украине на примере Польши. Проводится анализ польской формы децентрализации и избрание Украины определенной модели децентрализации. Проведено сравнение основных параметров развития экономики Украины и Польши в начале отдельных этапов реформы децентрализации, где взято за основной показатель динамики объема ВВП. Сформированы перспективы развития целесообразности избрания польского опыта децентрализации для внедрения в современных условиях.Досліджується сучасний стан здійснення реформи децентралізації в Україні, де висвітлюються питання становлення обраного євроінтеграційного вектору розвитку, фундаментальною основою якого стала необхідність здійснення реформи децентралізації адміністративно-територіального устрою України та інституту місцевого самоврядування. При обранні зарубіжного досвіду проведення подібної реформи взірцем став досвід Польщі. Проводиться аналіз польської форми децентралізації та обрання Україною визначеної моделі децентралізації. Здійснено порівняння основних параметрів розвитку економіки України і Польщі на початку окремих етапів реформи децентралізації, де взято за основний показник динаміки обсягу ВВП, інфляції.Визначено основні фактори, які впливають на процес децентралізації, зокрема і на економіку України загалом. Відокремлено проблеми, з якими зіштовхуються реформатори у процесі децентралізації адміністративно-територіального устрою України.Сформовано перспективи розвитку доцільності обрання польського досвіду децентралізації для впровадження у вітчизняних умовах