Mitochondria play an important role in the cell aging process. Changes in calcium homeostasis and/or increased reactive oxygen species (ROS) production lead to the opening of mitochondrial permeability transition pore (MPTP), depolarization of the inner mitochondrial membrane, and decrease of ATP production. Our work aimed to monitor age-related changes in the Ca2+ ion effect on MPTP and the ability of isolated rat liver mitochondria to accumulate calcium. The mitochondrial calcium retention capacity (CRC) was found to be significantly affected by the age of rats. Measurement of CRC values of the rat liver mitochondria showed two periods when 3 to 17-week old rats were tested. 3-week and 17-week old rats showed lower CRC values than 7-week old animals. Similar changes were observed while testing calcium-induced swelling of rat liver mitochondria. These findings indicate that the mitochondrial energy production system is more resistant to calcium-induced MPTP opening accompanied by the damaging effect of ROS in adult rats than in young and aged animals.
There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyze vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilized a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.
The incidence of cerebrovascular diseases increases significantly with aging. This study aimed to test the hypothesis that aging may influence the protein kinase A (PKA)-dependent vasodilation via RyR/BKCa pathway in the middle cerebral arteries (MCA). Male Sprague-Dawley rats were randomly divided into control (4-6 month-old) and aged (24-month-old) groups. The functions of MCA and ion channel activities in smooth muscle cells were examined using myograph system and patch-clamp. Aging decreased the isoproterenol/forskolin-induced relaxation in the MCA. Large-conductance Ca2+-activated-K+ (BKCa) channel inhibitor, iberiotoxin, significantly attenuated the forskolininduced vasodilatation and hyperpolarization in the young group, but not in the aged group. The amplitude and frequency of spontaneous transient outward currents (STOCs) were significantly decreased in the aged group. Single channel recording revealed that the mean open time of BKCa channels were decreased, while an increased mean closed time of BKCa channels were found in the aged group. The Ca2+/voltage sensitivity of the channels was decreased accompanied by reduced BKCa α and β1-subunit, the expression of RyR2, PKA-Cα and PKA-Cβ subunits were also declined in the aged group. Aging induced down-regulation of PKA/BKCa pathway in cerebral artery in rats. The results provides new information on further understanding in cerebrovascular diseases resulted from agerelated cerebral vascular dysfunction.
Agresivní řízení je významným fenoménem dnešní doby. Předložená studie popisuje tento jev a jeho konkrétní podoby, dále analyzuje možné příčiny a souvislosti. Ukazuje se, že agresivní řízení je složitým konstruktem, který je podmíněn multifaktoriálně a má širokou škálu projevů, od jejich mírných forem, až k řidičskému násilí. Společným prvkem agresivního řízení je způsob, kdy řidič ohrožuje nebo omezuje druhého řidiče a dochází ke vzniku riskantní situace. Řada studií vidí příčinu agresivního řízení v osobnostních proměnných (např. sensation-seeking, impulsivita, míra agresivity a iritability), přičemž poměrně dobrým prediktorem je i struktura osobnosti dle Big Five. Jiné studie považují za klíčové vnější situační faktory, jakými jsou dopravní kongesce, anonymita na silnicích a časový tlak. Přínosným je multifaktoriální přístup, který daný fenomén vidí jako výsledek působících vnitřních a vnějších faktorů. Významný vliv mají i sociální normy a celková řidičská kultura v dané zemi. V závěru studie uvádíme možná preventivní opatření pro zmírnění agresivních projevů při řízení, která by měla být komplexního charakteru a působit jak na jednotlivce (terapeutické programy pro agresivní řidiče, vzdělávání v autoškolách a preventivní kampaně), tak i na změnu vnějšího okolí (uspořádání dopravního prostředí s cílem minimalizovat stresory působící na řidiče). and Aggressive driving is an important phenomenon today. Our study describes aggressive driving, its specific manifestation, and analyses possible causes and the main context. It´s shown that aggressive driving is a complicated construct with multifactorial causes and has a wide range of manifestations, from mild forms to road rage. The main point of aggressive driving is such driver´s behaviour, which threatens or restricts other road users and leads to risky situations. Lots of studies find as the main reason for aggressive driving the personality characteristics (sensation-seeking, impulsivity, aggressiveness, and irritability), the personality structure Big Five seems to be a good predictor seems. Other studies rate as the key causes the situational factors, like traffic congestion, anonymity on the roads, and time pressure. The multifactorial approach evaluates this phenomenon as the result of internal and external factors. The important influencing factors are social norms and driving culture in a country. In conclusion, we discuss possible preventive measures for minimization of aggressive driving behaviour that should be complex and effect as individuals (therapeutic programs for aggressive drivers, education in driving schools preventive campaigns) so external environment (changes in road environment with the goal of minimization the driving pressure).
Scientific literacy is one of the crucial skills nec-essary for making informed decisions and eval-uating evidence. Despite the fact that the overall results of Slovak students in scientific literacy are lower than the average for OECD countries, there is still a lack of interventions focusing explicitly on fostering scientific literacy in the educational system. Therefore, this literature review aims to determine: 1. types of interven-tions that can be used to foster scientific literacy; 2. the main features of interventions responsible for their effectiveness. Authors conducted a con-tent analysis of 40 empirical scientific papers, focusing on two aspects of scientific literacy: scientific reasoning ability and attitudes toward science. The study indicates that scientific rea-soning ability can be effectively improved with the interventions focused on 1. scientific argu-mentation; 2. understanding nature of science; 3. process of scientific discovery. Interventions focused on improving attitudes toward science share similar characteristics as interventions fo-cused on scientific reasoning and can be classi-fied similarly. Other aspects, such as the level of guidance, teaching strategy, gender, and domain of the intervention can also play an important role. and Vedecká gramotnosť je považovaná za jednu zo základných spôsobilostí potrebných pri hodno-tení informácií a robení informovaných rozhod-nutí. Hoci slovenskí študenti skórujú v testoch vedeckej gramotnosti dlhodobo pod priemerom krajín OECD, jej rozvoju sa venuje len veľmi malá pozornosť a v edukačnom systéme je prí-tomná prevažne implicitne. Cieľom tejto práce bolo preto poskytnúť prehľad intervencií, kto-ré sú zamerané na zlepšovanie vedeckej gra-motnosti v stredoškolskom prostredí a popísať hlavné charakteristiky, ktoré môžu podporovať účinnosť týchto intervencií. V prehľade sa au-tori konkrétne zamerali na dve zložky vedeckej gramotnosti, ktorými sú vedecké myslenie a po-stoje k vede, a pomocou obsahovej analýzy ana-lyzovali zistenia 40 empirických štúdií. Štúdia poukazuje na to, že vedecké myslenie je možné efektívne rozvíjať cielenými intervenciami za-meranými na schopnosť vedeckej argumentácie, pochopenie podstaty vedy a proces vedeckého objavovania. Intervencie zamerané na zlepšova-nie postojov k vede zdieľajú podobné charak-teristiky ako intervencie zamerané na vedecké myslenie. Dôležitú rolu v podpore účinnosti in-tervencií majú úroveň podpory žiaka, výučbová stratégia, pohlavie a doména intervencie.
The article deals with the current case law on compensation for non-pecuniary damage with a focus on medical law. The aim is to outline the recent judicial practice of the highest courts of the Czech Republic in this area, to evaluate it, and, where appropriate, to comment critically on it. The article is divided into two chapters. The first deals with decisions focusing on the manner and extent of compensation for non-pecuniary damage, and the second with procedural aspects when bringing such claims before the court. and Článek se zabývá aktuální soudní praxí odčiňování nemajetkové újmy se zaměřením na oblast zdravotnického práva. Cílem je nastínit recentní soudní praxi vrcholných soudů ČR k této problematice, zhodnotit ji a případně i kriticky komentovat. Z hlediska struktury je článek rozdělen na dvě kapitoly. První se zabývá rozhodnutími zaměřenými na způsob a rozsah náhrady nemajetkové újmy, druhá procesními aspekty souvisejícími s uplatňováním tohoto typu nároků.
Cytochrome P450s (P450s) involved in insecticide resistance reduce the efficacy of insecticide-based vector control by rendering vector control ineffective. They are recorded in many species of vectors and have various constitutive and insecticide induction profiles. In this study, the isolation and prediction of the structure of a P450 from a strain of Aedes aegypti originating from Malaysia is reported. Quantitative mRNA expression of this gene and a previously reported P450, CYP4H28v2, in the developmental stages of the mosquito after exposure to sub-lethal concentrations of insecticides is also reported. The isolated P450, CYP4H31v2, is an allelic variant of CYP4H31 and contains several conserved motifs of P450s. The secondary structure of the protein is mostly made up of alpha helices and random coils. The tertiary structure was generated using homology modeling and was of good quality based on structure validation using protein structure assessment tools. CYP4H28v2 and CYP4H31v2 were differentially expressed in the developmental stages of the vector, with a significantly increased expression in adult males. The genes were significantly over-expressed in larvae exposed to deltamethrin and permethrin for 6 h. In the DDT-treated larvae, only CYP4H31v2 was significantly over-expressed after a 6 h exposure. Under-expression of the genes was predominant in larvae treated with the organophosphates malathion and temephos. Though the functions of these P450s are unknown, their response to induction by exposure to insecticides indicates the likely involvement of these genes in insecticide tolerance. and Fatma M. A. El-Garj, Mustafa F.F. Wajidi, Silas W. Avicor.
Cardiac fibrotization is a well-known process characteristic of many cardiac pathological conditions. The key element is excessive activation of cardiac fibroblasts, their transdifferentiation into myofibroblasts, increased production, and accumulation of extracellular matrix proteins, resulting in cardiac stiffness. The exact cellular mechanisms and molecular components involved in the process are not fully elucidated, but the SOCE mechanism could play an important role. Its key molecules are the molecular sensor of calcium in ER/SR - STIM and the highly selective calcium channels Orai located in the plasma membrane. This study aims to evaluate selected SOCEassociated genes in the activation of HCF cell culture by several known substances (phenylephrine, isoprenaline) that represent cardiovascular overload. After cell cultivation, cell medium was collected to measure the soluble collagen content. From the harvested cells, qRT-PCR was performed to determine the mRNA levels of the corresponding genes. The activation of cells was based on changes in the relative expression of collagen genes as well as the collagen content in the medium of the cell culture. We detected an increase in the expression of the Orai2 isoform, a change in the Orai1/Orai3 ratio and also an increase in the expression of the STIM2 isoform. These results suggest an increased activation of the SOCE mechanism under stress conditions of fibroblasts, which supports the hypothesis of fibroblast activation in pathological processes by altering calcium homeostasis through the SOCE mechanism., Róbert Čendula, Nikola Chomaničová, Adriana Adamičková, Andrea Gažová, Ján Kyselovič, Marek Máťuš., and Obsahuje bibliografii
In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.