The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary

Fingolimod was approved and reimbursed by the healthcare provider in Hungary for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS) in 2012. The present study aimed to assess the effectiveness, safety profile, and persistence to fingolimod in a real-life setting in Hungary in RRMS patients who were either therapy naïve before enrollment or have changed to fingolimod from another disease-modifying therapy (DMT) for any reason.This cross-sectional, observational study with prospective data collection was performed nationwide at 21 sites across Hungary. To avoid selection bias, sites were asked to document eligible patients in consecutive chronological order. Demographic, clinical, safety and efficacy data were analysed for up to 5 years from 570 consenting adult patients with RRMS who had received treatment with fingolimod for at least one year.69.6% of patients remained free from relapses for the whole study duration; in the first year, 85.1% of patients did not experience a relapse, which rose to 94.6% seen in the 5th year. Compared to baseline at study end, 28.2% had higher, and 9.1% had lower, meanwhile, 62.7% of the patients had stable EDSS scores. Overall, the annualized relapse rate decreased from 0.804 observed at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (77.0%, 82.1%, 85.2%, 89.7%, and 89.0% relative reduction, respectively) after 1, 2, 3, 4, and 5 years of treatment. The greatest reduction rate was seen in the group of therapy naïve patients. Treatment persistence on fingolimod after 60 months was 73.4%.In this nationwide Hungarian cohort, most patients under fingolimod treatment were free from relapses and disability progression. In addition, fingolimod has proven to be a well-tolerated DMT that has sustained its manageable safety profile, high efficacy, and positive benefit/risk ratio for up to 5 years in a real-life setting

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins – differing in cavity size, nature of substituents, degree of substitution and charge – the highest solubility increase was observed with sulfobutylether-β-cyclodextrin (SBE-β-CD). The inclusion complexation between POM and SBE-β-CD was further characterized with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), circular dichroism spectroscopy, fluorescence spectroscopy as well as X-ray powder diffraction method (XRD). Job plot titration by NMR and the AL-type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-β-CD could be a promising approach for developing more effective POM formulations with increased solubility

RENEB accident simulation exercise

Purpose: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event. Materials and methods: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants. The exercise was performed over 27 weeks and involved the network consisting of 28 institutes: 21 RENEB members, four candidates and three non-RENEB partners. Results: The duration of a single exercise never exceeded 10 days, while the response from the assisting laboratories never came later than within half a day. During each week of the exercise, around 4500 samples were reported by all service laboratories (SL) to be examined and 54 scenarios were coherently estimated by all laboratories (the standard deviation from the mean of all SL answers for a given scenario category and a set of data was not larger than 3 patient codes). Conclusions: Each participant received training in both the role of a reference laboratory (activating the network) and of a service laboratory (responding to an activation request). The procedures in the case of radiological event were successfully established and tested

Improvement of loadability in colorectal cancer patients by physiotherapy

Szakdolgozatomban egy onkológia területéről vett kórképet szeretnék bemutatni, a colorectalis carcinomát, melynek kezelése igen hosszadalmas és jelentős befolyással van a mindennapi tevékenységre. Kutatásomban a betegeim sugárkezelésük alatti állapotát vizsgáltam, vagyis azt, hogy a sugárkezelés negatív hatással van-e a fizikai állapotra, ezen belül az állóképességre, és ha igen, hogyan befolyásolja a betegek életminőségét. Két csoportba rendezve vizsgáltam és hasonlítottam össze a betegeim eredményét. Az egyik csoportba tartozók fizioterápiás programon vettek részt a sugárkezelésük alatt, míg a többiek a kontroll csoportba tartoztak, akik nem vettek részt tornán, viszont a sugárkezelésük előtt és után elvégezték a teszteket. Az aerob állóképességi tréning köztudottan pozitív hatással van a cardio- respiratorikus rendszerre, így célom az volt, hogy pozitív irányba tereljem a daganatos betegségben szenvedők állóképességét és életminőségüket javítsam. Mivel az inaktivitás nagy szerepet játszik a vastag-és végbél daganat kialakulásában, ezért ezzel a módszerrel lehetőségem nyílt megszerettetni és egyben megismertetni betegeimmel a mozgás örömét, amely meggyőződésem, hogy nagymértékben előmozdította életminőségük javulását. A mozgásterápia során egyéni és csoportos foglalkozásokra is sor került, így összesen a betegek 8 alkalmon vettek részt a kezelés alatt. A torna eszközökkel és zenével kiegészítve zajlott pulzuskontroll alatt. Aktív tornát és a levezetés során autostretchinget is alkalmaztam. A kezelés végén szignifikáns különbségeket találtam a két csoport összehasonlítása során. A tornán résztvevők között mérhető javulást figyelhetünk meg a terhelhetőségükre vonatkozóan, viszont a kontroll csoport tagjainál negatív irányú tendencia látható. Az életminőséget nézve a tornán résztvevők körében értünk el javulást, ezzel ellentétben sajnos a kontroll csoport tagjainál szembetűnő a negatív irányú változás.BSc/BAápolás és betegellátás (gyógytornász)magyarnappal

Fekete pedagógia - A testi fenyítés történeti dimenziója

Dolgozatomban a nevelés fogalmának, típusainak, illetve helyszíneinek ismertetése jelenik meg. Emellett a pedagógia egyik káros részének, a fekete pedagógia fogalmának és eredetének meghatározására kerül sor, ezzel közelítve a testi fenyítés témaköréhez. Bővebben a fekete pedagógiának alakulásáról olvashatunk a történelmi korszakokban. Fő hangsúly a testi fenyítésen, mint nevelési eszközön van, amely megértésének könnyítéséért a gyermekkor történelme is részletesebb bemutatásra kerül

Thematic hotels, as Hungarian tourist attractions

A tematikus szállodák ismertségének és látogatottságának vizsgálatát végeztem, valamint összehasonlítottam a Pangea és a Bambara Hotelt.felsőoktatási szakképzésTurizmus (felsőoktatási szakképzés)K

Body size awareness matters when dogs decide whether to detour an obstacle or opt for a shortcut

Abstract Body-awareness is one of the fundamental modules of self-representation. We investigated how body-awareness could contribute to dogs' decision making in a novel spatial problem where multiple solutions are possible. Family dogs (N = 68) had to obtain a treat from behind a transparent fence. They had two options: either detour around the fence (7 m), or take a shortcut through a doorway (2 m). We had three conditions: small door open, large door open, and doors closed. Our results indicated that dogs assess the size of the doorway, and if they find it too small, they decide to detour instead, while in the case of the open large door, they rather opted for the shortcut without hesitation. Shorter headed dogs tended to choose open doors more often, while longer headed dogs rather chose detours, probably because of their better peripheral vision. While body size awareness did not manifest differently in dogs with short or long heads, we showed for the first time a connection between head shape and physical cognition in dogs. We showed that dogs rely on their body-awareness in a naturalistic setting where multiple solutions exist simultaneously. Dogs make decisions without lengthy trial-and-error learning and choose between options based on their body-awareness

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Syndecan-1 is a transmembrane heparan sulfate proteoglycan which is indispensable in the structural and functional integrity of epithelia. Normal hepatocytes display strong cell surface expression of syndecan-1; however, upon malignant transformation, they may lose it from their cell surfaces. In this study, we demonstrate that re-expression of full-length or ectodomain-deleted syndecan-1 in hepatocellular carcinoma cells downregulates phosphorylation of ERK1/2 and p38, with the truncated form exerting an even stronger effect than the full-length protein. Furthermore, overexpression of syndecan-1 in hepatoma cells is associated with a shift of heparan sulfate structure toward a highly sulfated type specific for normal liver. As a result, cell proliferation and proteolytic shedding of syndecan-1 from the cell surface are restrained, which facilitates redifferentiation of hepatoma cells to a more hepatocyte-like phenotype. Our results highlight the importance of syndecan-1 in the formation and maintenance of differentiated epithelial characteristics in hepatocytes partly via the HGF/ERK/Ets-1 signal transduction pathway. Downregulation of Ets-1 expression alone, however, was not sufficient to replicate the phenotype of syndecan-1 overexpressing cells, indicating the need for additional molecular mechanisms. Accordingly, a reporter gene assay revealed the inhibition of Ets-1 as well as AP-1 transcription factor-induced promoter activation, presumably an effect of the heparan sulfate switch