Legality of so-called “epidemic fees” Wilk, Anna
Zeszyty Naukowe Wyższej Szkoły Finansów i Prawa w Bielsku-Białej,
06/2020, Letnik:
24, Številka:
2
Journal Article
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The article refers to the problem of the so-called "epidemic fees", collected by the entrepreneurs during the epidemic in order to compensate increased costs of running a business in a sanitary ...regime. The Author analyzes whether collecting of such fees is acceptable in the light of actual legal status. The problem is examined from the civil law point of view, with particular emphasis on the provisions referring to abusive clauses, exploitation and limitations of the freedom of contract due to the principles of social coexistence. The Author also tries to define the requirements that such fees should meet to be considered acceptable, as well as compliance with legal provisions referring to practicing a certain profession (for example a physician, a dentist), as well as the principles of professional ethics, proper and prior informational obligation and adjustment of the fee amount to the real and reasonable costs of running a business in an increased sanitary regime.
The article refers to the subject matter of the responsibility of the Roman Catholic Church and its legal persons for the damages related to sexual abuse of children committed by priests. The Author ...quotes relevant American experience as well possible bases of liability to be found in Polish law. The article also analyzes possible problems connected with practical application of legal regulations referring to vicarious liability in the light of the specifics of the Church.
The paper refers to the problem of prohibition of competition imposed on the members of the board of directors and the supervisory board of a cooperative. The Author analyses the concepts of ..."competitive business" and "competitive activity" and their mutual relationship, as well as the consequences of non-compliance with the prohibition. On the basis of interpretation of the existing legal provisions and views of judicature, the Author enunciates de lege ferenda conclusions in terms of their clarification and elimination of doubts.
Fenofibrate (FF) is a common lipid-lowering drug and a potent agonist of the peroxisome proliferator-activated receptor alpha (PPARα). FF and several other agonists of PPARα have interesting ...anticancer properties, and our recent studies demonstrate that FF is very effective against tumor cells of neuroectodermal origin. In spite of these promising anticancer effects, the molecular mechanism(s) of FF-induced tumor cell toxicity remains to be elucidated. Here we report a novel PPARα-independent mechanism explaining FF's cytotoxicity in vitro and in an intracranial mouse model of glioblastoma. The mechanism involves accumulation of FF in the mitochondrial fraction, followed by immediate impairment of mitochondrial respiration at the level of complex I of the electron transport chain. This mitochondrial action sensitizes tested glioblastoma cells to the PPARα-dependent metabolic switch from glycolysis to fatty acid β-oxidation. As a consequence, prolonged exposure to FF depletes intracellular ATP, activates the AMP-activated protein kinase-mammalian target of rapamycin-autophagy pathway, and results in extensive tumor cell death. Interestingly, autophagy activators attenuate and autophagy inhibitors enhance FF-induced glioblastoma cytotoxicity. Our results explain the molecular basis of FF-induced glioblastoma cytotoxicity and reveal a new supplemental therapeutic approach in which intracranial infusion of FF could selectively trigger metabolic catastrophe in glioblastoma cells.
The article presents the e valuation o f h ow suitable waste from the production of aggregates in quarries could be in earthwork using the example of screen-outs from Krosno sandstone. The waste, ...called screen-out, is characterised by an uncontrolled content of dust and clay fractions. Screen-outs have a relatively low bearing ratio (CBR not exceeding 20%) and a tendency to heave due to frost (SE <35). To check whether the geotechnical properties can be improved, mixtures with 2%, 5%, and 8% binders, such as lime, fly ash, and two road binders with lime, fly ash, and cement were prepared. The analysis was based on the results of the CBR and compressive strength tests. The use of mineral binders caused the value of the immediate CBR to increase compared to the screen-out itself from a dozen to as much as 50%. For a binder containing 20% Portland clinker, the CBR was about 60% after 4 days of saturation, while for a binder containing up to 50% Portland clinker, it was over 200%. The value of compressive strength after 28 days of maturing ranged from about 100 kPa to 1 MPa for all mixes tested. The lowest values were obtained for screen-outs activated with fly ash, and the highest for road binder with cement content of up to 50%.
Anti-neoplastic potential of calorie restriction or ligand-induced activation of peroxisome proliferator activated receptors (PPARs) has been demonstrated in multiple studies; however, mechanism(s) ...by which tumor cells respond to these stimuli remain to be elucidated. One of the potent agonists of PPARα, fenofibrate, is a commonly used lipid-lowering drug with low systemic toxicity. Fenofibrate-induced PPARα transcriptional activity is expected to shift energy metabolism from glycolysis to fatty acid β-oxidation, which in the long-term, could target weak metabolic points of glycolysis-dependent glioblastoma cells. The results of this study demonstrate that 25 μM fenofibrate can effectively repress malignant growth of primary glial tumor cells and glioblastoma cell lines. This cytostatic action involves G
1
arrest accompanied by only a marginal level of apoptotic cell death. Although the cells treated with 25 μM fenofibrate remain arrested, the cells treated with 50 μM fenofibrate undergo massive apoptosis, which starts after 72 h of the treatment. This delayed apoptotic event was preceded by FoxO3A nuclear accumulation, FoxO3A phosphorylation on serine residue 413, its elevated transcriptional activity and expression of FoxO-dependent apoptotic protein, Bim. siRNA-mediated inhibition of FoxO3A attenuated fenofibrate-induced apoptosis, indicating a direct involvement of this transcription factor in the fenofibrate action against glioblastoma. These properties of fenofibrate, coupled with its low systemic toxicity, make it a good candidate in support of conventional therapies against glial tumors.
Penile erection is a hemodynamic process consisting of 2 synchronized components in which the first (active) requires proper vascular endothelium functioning, whereas the second one (passive) is ...based on a veno-occlusive mechanism. Antihypertensive treatment reduces the passive component, often leading to the development of erectile dysfunction (ED), but lifestyle modifications can improve the sexual functioning. The study aimed to evaluate the association between blood pressure (BP) reduction caused by cardiovascular training and the intensity of ED in men with coronary heart disease. A total of 101 men (mean age 59.50 ± 7.93) with ED treated invasively for coronary heart disease and subjected to cardiac rehabilitation were enrolled. Patient characteristics, the International Index of Erectile Function 5 (IIEF-5) questionnaire (IIEF-5), and BP values were collected at baseline and after 6 months of cardiac rehabilitation and were analyzed. Cardiac rehabilitation led to a significant reduction of 5.08 mm Hg in systolic BP (p <0.001) and of 1.60 mm Hg in diastolic BP (p <0.001). The IIEF-5 score (EQ) significantly increased (median 15, interquartile range 11 to 19 vs median 18, interquartile range 12 to 21, p <0.001). Greater improvement in sexual performance was significantly negatively correlated with age, concentration of triglycerides, and high-density lipoprotein, whereas it was positively correlated with the presence of diabetes and baseline IIEF-5 score. After excluding patients with diabetes, a greater decrease in systolic BP was found to be significantly associated with greater improvement in erectile performance. In conclusion, a reduction of arterial BP caused by cardiac training is accompanied by improvement in erectile performance. This effect is the strongest in patients with hypertension and those with dyslipidemia.
Abstract
Background
Glioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and ...statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARα) that can switch energy metabolism from glycolysis to fatty acid β-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal.
Methods
The effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARα activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were analyzed in human glioma cell lines.
Results
Fenofibrate treatment attenuated IGF-I signaling responses and repressed cell motility of LN-229 and T98G Glioma cell lines. In the absence of fenofibrate, specific inhibition of the IGF-IR had only modest effects on Glioma cell motility. Further experiments revealed that PPARα-dependent accumulation of ROS is a strong contributing factor in Glioma cell lines responses to fenofibrate. The ROS scavenger, N-acetyl-cysteine (NAC), restored cell motility, improved mitochondrial potential, and increased ATP levels in fenofibrate treated Glioma cell lines.
Conclusions
Our results indicate that although fenofibrate-mediated inhibition of the IGF-IR may not be sufficient in counteracting Glioma cell dispersal, PPARα-dependent metabolic switch and the resulting ROS accumulation strongly contribute to the inhibition of these devastating brain tumor cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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