multidomain
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- MeSH
- bachor fyziologie mikrobiologie MeSH
- Bacteria enzymologie genetika metabolismus MeSH
- bakteriální geny genetika MeSH
- financování vládou MeSH
- otevřené čtecí rámce genetika MeSH
- polymerázová řetězová reakce metody využití MeSH
- sekvenční analýza MeSH
- xylany metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Present demographic changes demonstrate that the number of elderly people is growing at a frenetic pace. This shift in population consequently results in many social and economic problems, which burden the social and economic systems of countries. The aging process is associated with age-related diseases, the most common of which are dementia and Alzheimer's disease, whose main symptom is a decline in cognitive function, especially memory loss. Unfortunately, it cannot be cured. Therefore, alternative approaches, which are cost-effective, safe, and easy to implement, are being sought in order to delay and prevent cognitive impairment. The purpose of this review was to explore the effect of multidomain lifestyle intervention strategies on the delay and/or prevention of cognitive impairment in healthy older individuals. The methods are based on a literature review of available sources found on the research topic in three acknowledged databases: Web of Science, Scopus, and PubMed. The results of the identified original studies reveal that multidomain lifestyle interventions generate significant effects. In addition, these interventions seem feasible, cost-effective, and engaging. Thus, there is a call for the implementation of effective lifestyle prevention programs, which would involve goal-setting and would focus on the prevention of crucial risk factors threatening the target group of elderly people, who are at risk of cognitive decline and dementia.
- MeSH
- cvičení * MeSH
- lidé MeSH
- rizikové faktory MeSH
- zdravé stárnutí * MeSH
- životní styl * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
349 s. : il.
Psoriatická artritida (PsA) se manifestuje řadou skeletálních a mimoskeletálních projevů, přičemž mezi druhou skupinu patří postižení kůže, nehtů, dále pak akutní přední uveitida a idiopatické střevní záněty. Jde o heterogenní onemocnění s rozlišnou závažností projevů. Autor hodnotí účinnost secukinumabu u jednotlivých domén PsA, a to konkrétně u artritidy, rentgenové progrese, vlivu na entezitidy, daktylitidy, axiální postižení a na nehtovou psoriázu. U každé z těchto domén uvádí data z randomizovaných kontrolovaných studií a doplňuje je výsledky z národního registru biologické léčby ATTRA. Na našem pracovišti jsme sledovali dlouhodobou účinnost celkem u 426 pacientů s PsA. Přežívání na léčbě bylo po třech letech 64,6 %. Po dvou letech léčby došlo k signifikantnímu poklesu skóre aktivity choroby u 28 kloubů vypočteného podle hladiny C-reaktivního proteinu (Disease Activity Score in 28 joint for rheumatoid arthritis using C-reactive protein, DAS28-CRP-FW), přičemž 54 % pacientů splňovalo kritéria remise (DAS28-CRP-FW < 2,6) a 74,8 % pak kritérium stavu nízké aktivity DAS28-CRP-FW < 3,2). V registru ATTRA byly dostupné údaje o přítomnosti entezitidy paty u 417 pacientů. Entezitida paty se na začátku léčby vyskytovala u 12,2 % pacientů po 24 měsících léčby, pak u 1,5 % pacientů. Daktylitida se vyskytovala v registru ATTRA na začátku léčby u 22 % pacientů a po dvou letech léčby se snížila na 4,7 %. Střední a závažné postižení nehtů se v registru ATTRA se vyskytovalo u 33,2 % pacientů na začátku léčby a u 33,2 % pacientů a po dvou letech léčby u 3,8 % pacientů.
Psoriatic arthritis (PsA) is characterized by a number of skeletal and extra-skeletal manifestations, which include skin and nail involvement, acute anterior uveitis, and idiopathic intestinal inflammation. These are heterogeneous diseases that vary in the severity of their manifestations. The author assesses the efficacy of secukinumab across different domains of PsA, such as arthritis, radiographic progression, the effect on enthesitis, dactylitis, axial involvement, and nail psoriasis. The article presents data from randomized controlled trials and complements them with results from the ATTRA National Registry of Biologic Therapies. At our institution, we have monitored the long-term efficacy in a total of 426 patients with PsA. Survival on treatment at three years was 64.6%. After two years of treatment, there was a significant decrease in the Disease Activity Score in 28 joints calculated using C-reactive protein (DAS28-CRP-FW) for rheumatoid arthritis, with 54% of patients meeting remission criteria (DAS28-CRP-FW < 2.6) and 74.8% meeting criteria for low disease activity status (DAS28-CRP-FW < 3.2). Data on the presence of heel enthesitis in 417 patients were available in the ATTRA registry. Heel enthesitis was present in 12.2% of patents at the start of treatment and then in 1.5% of patients after 24 months of treatment. Dactylitisoccurred in 22% of patients in the ATTRA registry at the start of treatment and decreased to 4.7% after two years of treatment. Moderate and severe nail involvement was reported in 33.2% of patients in the ATTRA registry at the start of treatment, and this decreased to 3.8% of patients after two years of treatment.
- Klíčová slova
- secukinumab,
- MeSH
- humanizované monoklonální protilátky MeSH
- klinická studie jako téma MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- psoriatická artritida * farmakoterapie patologie MeSH
- psoriáza farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Při poskytování perinatální paliativní péče je nezbytná spolupráce mnohých odborností. Vnímání a porozumění možnostem a současným nástrojům specializované paliativní péče se mezi odbornostmi i jednotlivými profesionály liší. Potřebný validovaný dotazník, který by vnímání mapoval, v českém i v mezinárodním prostředí dosud chybí. Předkládáme proto dotazník pro expertní vícedoménové hodnocení perinatální paliativní péče (Palliative peRInatal Multidomain Assessment [PRIMA]). Dotazník prošel dvoukolovou externí validací a hodnocením vnitřní konzistence (Cronbachovo α pro celý dotazník 0.799 [95% konfidenční interval 0.550–0.878], pro podotázky na aktuální stav 0.767 [0.544–0.877] a podotázky na ideální stav 0.867 [0.763–0.916]).
Perinatal palliative care is based on the cooperation of multiple workers with multiple areas of expertise. Perceptions and understanding of the possibilities and current tools of specialised palliative care vary between specialties and between professionals. The necessary validated questionnaire, which would map the perception of individual health professionals in the Czech and international environment, is still missing. The Palliative peRInatal Multidomain Assessment (PRIMA) questionnaire is presented and externally validated in a two-round process. Internal consistency is calculated (Cronbach’s α for the whole questionnaire, for the subset of items about the actual state, and the subset of items about the ideal state is 0.799 [95% confidence interval 0.550–0.878], 0.767 [0.544–0.877], and 0.867 [0.763–0.916] respectively).
- Klíčová slova
- perinatální paliativní péče,
- MeSH
- lidé MeSH
- nemoci plodu MeSH
- novorozenec MeSH
- paliativní péče * MeSH
- perinatální péče * MeSH
- perinatální smrt MeSH
- průzkumy a dotazníky MeSH
- těhotenství MeSH
- vrozené vady MeSH
- zdravotní péče - kvalita, dosažitelnost a hodnocení MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
Alzheimer disease (AD) is a life-limiting neurodegenerative disorder that disproportionately affects women. Indeed, sex and gender are emerging as crucial modifiers of diagnostic and therapeutic pathways in AD. This Review provides an overview of the interactions of sex and gender with important developments in AD and offers insights into priorities for future research to facilitate the development and implementation of personalized approaches in the shifting paradigm of AD care. In particular, this Review focuses on the influence of sex and gender on important advances in the treatment and diagnosis of AD, including disease-modifying therapies, fluid-based biomarkers, cognitive assessment tools and multidomain lifestyle interventional studies.
- MeSH
- Alzheimerova nemoc * terapie diagnóza epidemiologie MeSH
- biologické markery MeSH
- lidé MeSH
- pohlavní dimorfismus * MeSH
- sexuální faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Proteins are naturally formed by domains edging their functional and structural properties. A domain out of the context of an entire protein can retain its structure and to some extent also function on its own. These properties rationalize construction of artificial fusion multidomain proteins with unique combination of various functions. Information on the specific functional and structural characteristics of individual domains in the context of new artificial fusion proteins is inevitably encoded in sequential order of composing domains defining their mutual spatial positions. So the challenges in designing new proteins with new domain combinations lie dominantly in structure/function prediction and its context dependency. Despite the enormous body of publications on artificial fusion proteins, the task of their structure/function prediction is complex and nontrivial. The degree of spatial freedom facilitated by a linker between domains and their mutual orientation driven by noncovalent interactions is beyond a simple and straightforward methodology to predict their structure with reasonable accuracy. In the presented manuscript, we tested methodology using available modeling tools and computational methods. We show that the process and methodology of such prediction are not straightforward and must be done with care even when recently introduced AlphaFold II is used. We also addressed a question of benchmarking standards for prediction of multidomain protein structures-x-ray or Nuclear Magnetic Resonance experiments. On the study of six two-domain protein chimeras as well as their composing domains and their x-ray structures selected from PDB, we conclude that the major obstacle for justified prediction is inappropriate sampling of the conformational space by the explored methods. On the other hands, we can still address particular steps of the methodology and improve the process of chimera proteins prediction.
The cyclin-dependent kinase (CDK) inhibitor p21WAF1/CIP1 is a multidomain, multifunctional protein and a candidate tumor suppressor. Here, we show that, among rationally designed and tumor-associated mutants of human p21 ectopically expressed in U-2-OS cells, those that are selectively deficient in binding to either cyclin or CDK are partially impaired in inhibiting endogenous CDK activities but efficiently promote assembly of active cyclin D/CDK4(6) complexes. These results provide mechanistic insights into the p21-cyclin/CDK interplay in vivo and suggest a functional subclassification of tumor-specific aberrations of p21. Intriguingly, the subclass exemplified by the melanoma-derived N50S mutant may promote tumorigenesis, by both attenuating CDK-inhibitory function and concomitantly activating the proto-oncogenic cyclin D-dependent kinases.
- MeSH
- bodová mutace MeSH
- cyklin D MeSH
- cyklin-dependentní kinasa 4 MeSH
- cyklin-dependentní kinasa 6 MeSH
- cyklin-dependentní kinasy metabolismus MeSH
- cykliny genetika metabolismus fyziologie MeSH
- inhibitor p21 cyklin-dependentní kinasy MeSH
- lidé MeSH
- melanom metabolismus MeSH
- nádorové buňky kultivované MeSH
- nádorové proteiny genetika fyziologie MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- protoonkogenní proteiny * MeSH
- tumor supresorové geny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
