INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.

• Klíčová slova
• Alzheimer's disease (AD), air pollution, air–liquid interface (ALI), heat shock protein (HSP), next‐generation sequencing (NGS), nuclear factor erythroid 2–related factor 2 (NRF2), traffic emissions, traffic‐related air pollution (TRAP) olfactory mucosa (OM),
• MeSH
• Alzheimerova nemoc * genetika   metabolismus   MeSH
• čichová sliznice metabolismus   MeSH
• epigenomika MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• mikro RNA metabolismus   genetika   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• výfukové emise vozidel * toxicita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 MeSH
• látky znečišťující vzduch MeSH
• mikro RNA MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• výfukové emise vozidel * MeSH

Although impacts of extremely cold temperatures on human health have been widely studied, adverse effects of other extreme weather phenomena have so far received much less attention. We employed a high-quality long-term mortality time series (1982-2017) to evaluate impacts of extreme winter weather in the Czech Republic. We aimed to clarify whether compound events of extreme weather cause larger impacts on mortality than do each type of extreme if evaluated individually. Using daily data from the E-OBS and ERA5 datasets, we analyzed 9 types of extreme events: extreme wind gust, precipitation, snowfall, and sudden temperature and pressure changes. Relative mortality deviations from the adjusted baseline were used to estimate the immediate effect of the selected extreme events on excess mortality. The impact was adjusted for the effect of extreme cold. Extreme events associated with sudden rise of minimum temperature and pressure drops had generally significant impact on excess mortality (3.7% and 1.4% increase). The impacts were even more pronounced if these events occurred simultaneously or were compounded with other types of extremes, such as heavy precipitation, snowfall, maximum temperature rise, and their combinations (increase as great as 14.4%). Effects of some compound events were significant even for combinations of extremes having no significant impact on mortality when evaluated separately. On the other hand, a "protective" effect of pressure increases reduced the risk for its compound events. Meteorological patterns during extreme events linked to excess mortality indicate passage of a low-pressure system northerly from the study domain. We identified extreme winter weather events other than cold temperatures with significant impact on excess mortality. Our results suggest that occurrence of compound extreme events strengthen the impacts on mortality and therefore analysis of multiple meteorological parameters is a useful approach in defining adverse weather conditions.

• Klíčová slova
• Central Europe, Compound event, Extreme winter weather, Mortality, Sudden change,
• MeSH
• lidé MeSH
• mortalita MeSH
• nízká teplota * MeSH
• počasí * MeSH
• roční období MeSH
• teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

BACKGROUND: Information and communication technology (ICT) use among older adults has been on the rise in recent years. However, the predictors and mechanisms behind older adults' acceptance and use of ICT are not clear. OBJECTIVE: This study aimed to systematically describe ICT usage among Czech older adults and to evaluate the factors influencing their ICT use and readiness to use digital technology to promote health (eHealth readiness). The primary focus was on psychological factors and the role of persons close to older adults. METHODS: The research utilized cross-sectional survey data from a quota-based sample of Czech older adults (>50 years) and persons close to them further referred to as close persons (N=250 dyads). A structural equation modeling framework was used to evaluate relationships between psychological factors, ICT use, and eHealth readiness. RESULTS: Czech older adults' use of ICT is low with the exception of cell phone usage (cell phone usage by 173/250, 69.2%; other devices used by 50/250, 20.0% of older adults or less). Apart from age (β=-.21; P<.001), eHealth readiness was predicted by ICT use (β=.65; P<.001). eHealth readiness was also indirectly affected by the need for cognitive closure (NFCC): individuals with a high need for closure perceived more barriers to ICT (β=.23; P=.01) and more reported barriers were linked to lower ICT usage (β=-.21; P=.001). The expected positive relationships between eHealth readiness of persons close to older adults and ICT use and eHealth readiness of older adults were not significant, but the total effect of eHealth readiness of persons close to older adults on eHealth readiness of older adults was positive and significant (β=.18; P=.01), indicating some level of influence of persons close to them on older adults' attitudes and behaviors. CONCLUSIONS: This study provided the first systematic examination of Czech older adults' ICT usage and eHealth readiness. Novel predictors (NFCC and close persons' variables) were evaluated and yielded actionable results. More research is needed to clarify the role of persons close to older adults.

• Klíčová slova
• eHealth, elderly, information technology, need for cognitive closure,
• MeSH
• lidé MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• stárnutí psychologie   MeSH
• telemedicína metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Genes encoding the KDM5 family of transcriptional regulators are disrupted in individuals with intellectual disability (ID). To understand the link between KDM5 and ID, we characterized five Drosophila strains harboring missense alleles analogous to those observed in patients. These alleles disrupted neuroanatomical development, cognition and other behaviors, and displayed a transcriptional signature characterized by the downregulation of many ribosomal protein genes. A similar transcriptional profile was observed in KDM5C knockout iPSC-induced human glutamatergic neurons, suggesting an evolutionarily conserved role for KDM5 proteins in regulating this class of gene. In Drosophila, reducing KDM5 changed neuronal ribosome composition, lowered the translation efficiency of mRNAs required for mitochondrial function, and altered mitochondrial metabolism. These data highlight the cellular consequences of altered KDM5-regulated transcriptional programs that could contribute to cognitive and behavioral phenotypes. Moreover, they suggest that KDM5 may be part of a broader network of proteins that influence cognition by regulating protein synthesis.

• MeSH
• aktivace transkripce MeSH
• Drosophila melanogaster genetika   metabolismus   MeSH
• Drosophila genetika   metabolismus   MeSH
• histondemethylasy metabolismus   genetika   MeSH
• lidé MeSH
• mentální retardace genetika   metabolismus   MeSH
• mitochondrie metabolismus   genetika   MeSH
• neurony * metabolismus   MeSH
• proteiny Drosophily * genetika   metabolismus   MeSH
• proteosyntéza MeSH
• ribozomální proteiny * genetika   metabolismus   MeSH
• ribozomy metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histondemethylasy MeSH
• KDM5C protein, human MeSH Prohlížeč
• Lid protein, Drosophila MeSH Prohlížeč
• proteiny Drosophily * MeSH
• ribozomální proteiny * MeSH

The contemporary state of the sub-discipline of endocrinology within the framework of internal medicine is generally considered rather desolate, but so far actual data were lacking. Based on an analysis of data provided by regional specialists in the Czech Republic and by regional (district) specialists in internal medicine in Slovak republic it may be said that in the majority of health institutions the number of endocrinologists does not reach even the unsatisfactory standard (i. e. 1 endocrinologist per 150 to 250,000 population), that specialized training of endocrinologists, specialists in internal medicine and other specialist is not ensured, that there are not adequate numbers of community doctors and factory medical officers, that there are not adequate capacities of specialized laboratory examinations and that adequate collaboration with other disciplines is not ensured (the position is in particular alarming as regards immunological methods and cytological processing of specimens obtained by aspiration biopsy from the thyroid gland. With regard to these data the authors recommend to raise the numbers of endocrinologists so that in institutions corresponding to hospitals with policlinics type II there will be one endocrinologist per 50-100,000 population, to improve the standard and availability of auxiliary examinations, to ensure endocrinological in-patient care at the level of hospitals with policlinics type III and to create specialized centres within the framework of the research base or university hospitals. It is important to resolve the link between endocrinology and other disciplines (paediatrics, gynaecology etc). It is also essential to coordinate closely therapy, education and research, Federal coordination is essential.

• MeSH
• endokrinologie * MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Geografické názvy
• Československo MeSH