INTRODUCTION: Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published an update on the Global Strategy for Prevention, Diagnosis and Management of COPD, introducing a new classification of chronic obstructive pulmonary disease (COPD). Our aim was to assess the prognostic value of the new GOLD classification system in comparison with the previous GOLD classification systems (GOLD stages I-IV and GOLD groups A-D) and the BODE index. METHODS: We used the data of 784 patients with COPD from the Czech Multicenter Research Database of COPD. Patient survival was analyzed with the use of Kaplan-Meier estimate and Cox model of proportional risks. ROC analysis and area under curve (AUC) were used for comparison of GOLD classifications and BODE index. The analyses were performed with the use of software R (version 4.2.0). RESULTS: We analyzed data of 782 patients with complete data on GOLD classifications. The study population comprised 72.9% of men, 89.1% current or former smokers, with a mean age of 66.6 years, a mean BMI of 27.4 and a mean FEV1 44.9% of predicted. Probability of 5-year survival differed by GOLD classification. Application of the 2023 GOLD classification showed increased risk of death in group B (HR 1.82, 95% CI 1.14-2.92; p = 0.013) and in group E (HR 2.48, 95% CI 1.54-3.99; p˂0.001). The ROC analysis showed that the overall prognostic value of the 2023 GOLD classification was similarly weak to previous A-D GOLD classification schemes (AUCs 0.557-0.576) and was lower compared to the GOLD 1-4 system (AUC 0.614) and even lower when compared to the BODE index (AUC 0.715). CONCLUSION: We concluded that the new GOLD classification system has poor prognostic properties and that specific prediction tools (eg, the BODE index) should be used for mortality risk assessment.

• MeSH
• chronická obstrukční plicní nemoc * diagnóza   terapie   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• prognóza MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Background: Adherence to inhaled medication constitutes a major problem in patients with chronic obstructive pulmonary disease (COPD) globally. However, large studies evaluating adherence in its entirety and capturing a large variety of potentially associated factors are still lacking. Objective: To study both elementary types of adherence to chronic inhaled COPD medication in "real-life" COPD patients and to assess relationships with a wide-ranging spectrum of clinical parameters. Methods: Data from the Czech Multicentre Research Database (CMRD) of COPD, an observational prospective study, were used. Overall adherence (OA) was evaluated with Morisky Medication Adherence Scale (©MMAS-4) and adherence to an application technique (A-ApplT) with the Five Steps Assessment. Mann-Whitney U test, Spearman's correlation, and logistic regression were used to explore relationships between variables. Results: Data of 546 participants (69.6% of all patients from the CMRD) were analyzed. Two-thirds self-reported optimal OA, but only less than one-third demonstrated A-ApplT without any error. OA did not correlate with A-ApplT. Next, better OA was associated with higher education, a higher number of inhalers, a lower rate of exacerbations, poorer lung function, higher degree of upper respiratory tract symptoms (SNOT-22), absence of depressive symptoms, ex-smoking status, regular mouthwash after inhaled corticosteroids (ICS), and flu vaccination. By contrast, better A-ApplT was associated with a lower number of inhalers, better lung function, and regular mouthwash after ICS. Independent predictors of nonoptimal OA included lower degree of education, absence of flu vaccination, anemia, depression, and peptic ulcer history, whereas independent predictors of lower A-ApplT were lower education, absence of regular mouthwash after ICS, and higher COPD Assessment Test score. Conclusions: Parameters associated with OA and A-ApplT differ, and those associated with both adherence domains are sometimes associated inversely. Based on this finding, we understand these as two separate constructs with an overlap.

• Publikační typ
• časopisecké články MeSH

(1) Background: Microorganisms originating from the microflora of the oral cavity are the main cause of the inflammatory diseases of the dental pulp and periapical periodontium, as well as the failure of endodontic treatment. The subsequent root canal treatment is not able to remove all the pathogens, and a small number of viable bacteria remain in the dentine tubules, which must be sealed by endodontic sealers. These sealers should have at least a bacteriostatic effect to prevent the remaining bacteria from reproducing. The aim of this study is to compare the short-term antibacterial activity of three endodontic sealers based on poly-epoxy resin, zinc oxide-eugenol and calcium silicate with a calcium hydroxide-based sealer. Calcium hydroxide is used as temporary intracanal medicament and, thus, should show significant antibacterial activity. (2) Methods: A total of 25 bovine dentine samples infected with Enterococcus faecalis were used in this study. After the sealer placement and a 24 h incubation period, the root canal walls were scraped, and the suspension of dentine fillings was used for a semi-quantitative evaluation of microbial growth. (3) Results: The poly-epoxide resin-based sealer ADSealTM showed significant antibacterial properties. (4) Conclusions: The highest antibacterial activity was shown in poly-epoxide resin-based sealer group, followed by the zinc oxide-eugenol-based sealer and calcium silicate-based sealer.

• Publikační typ
• časopisecké články MeSH

The 3'-5', 3'-5' cyclic dinucleotides (3'3'CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host innate immunity. Here, we profiled the substrate specificity of four bacterial dinucleotide synthases from Vibrio cholerae (DncV), Bacillus thuringiensis (btDisA), Escherichia coli (dgcZ), and Thermotoga maritima (tDGC) using a library of 33 nucleoside-5'-triphosphate analogues and then employed these enzymes to synthesize 24 3'3'CDNs. The STING affinity of CDNs was evaluated in cell-based and biochemical assays, and their ability to induce cytokines was determined by employing human peripheral blood mononuclear cells. Interestingly, the prepared heterodimeric 3'3'CDNs bound to the STING much better than their homodimeric counterparts and showed similar or better potency than bacterial 3'3'CDNs. We also rationalized the experimental findings by in-depth STING-CDN structure-activity correlations by dissecting computed interaction free energies into a set of well-defined and intuitive terms. To this aim, we employed state-of-the-art methods of computational chemistry, such as quantum mechanics/molecular mechanics (QM/MM) calculations, and complemented the computed results with the {STING:3'3'c-di-ara-AMP} X-ray crystallographic structure. QM/MM identified three outliers (mostly homodimers) for which we have no clear explanation of their impaired binding with respect to their heterodimeric counterparts, whereas the R2 = 0.7 correlation between the computed ΔG'int_rel and experimental ΔTm's for the remaining ligands has been very encouraging.

• MeSH
• Bacillus thuringiensis enzymologie   ultrastruktura   MeSH
• cytokiny chemie   genetika   MeSH
• Escherichia coli enzymologie   ultrastruktura   MeSH
• krystalografie rentgenová MeSH
• kvantová teorie MeSH
• leukocyty mononukleární chemie   enzymologie   MeSH
• lidé MeSH
• membránové proteiny chemie   genetika   ultrastruktura   MeSH
• nukleotidy biosyntéza   chemie   genetika   MeSH
• přirozená imunita genetika   MeSH
• substrátová specifita MeSH
• Thermotoga maritima enzymologie   ultrastruktura   MeSH
• Vibrio cholerae enzymologie   ultrastruktura   MeSH
• vztahy mezi strukturou a aktivitou * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

Úvod a cíl: Sanace kariézní léze patří ve stomatologii již odedávna mezi základní výkony, avšak i v dnešní době stále není zcela jednotný přístup k tomuto ošetření v případě kazu blízkého zubní dřeni. Existují tři rozdílné techniky ošetření, které mají své výhody i nevýhody, nicméně jejich společným cílem je zachování vitality zubu. První přístup k ošetření je totální exkavace všech kariézních tkání se zhotovením definitivní výplně, druhým způsobem ošetření je selektivní exkavace s ponecháním malého množství změklých tkání pulpálně a zhotovením definitivní výplně. Třetí technikou je sekvenční exkavace, což znamená dvoudobé ošetření s postupným odstraněním všech kariézních tkání. Toto přehledové sdělení je zaměřeno právě na třetí typ ošetření, tedy na odloženou exkavaci a možnosti provedení s využitím různých remineralizačních materiálů. Metody: Pro tento přehledový článek byly vyhledány studie v anglickém jazyku za pomoci klíčových slov (kaz blízký dřeni, odložená exkavace, nepřímé překrytí zubní dřeně, hydroxid vápenatý, skloionomerní cement, kalciumsilikátový cement, kalciumfosfátový cement) a jejich obměnou s cílem shrnout současné poznatky o metodě odložené exkavace a materiálech používaných v této indikaci. Vyhledávalo se v databázích PubMed, Web of Science a Cochrane Library a zdrojích tuzemské literatury. Byly vybrány studie především z časopisů s impakt faktorem a vydaných v rozmezí let 2010 až 2020. Pro hlubší pochopení historického vývoje problematiky byla literatura doplněna i o několik publikací z druhé poloviny minulého století. Závěr: Ošetření hlubokého kazu se zachováním vitality je v dnešní době velmi diskutované téma a stále není jednotný postup, jak tento výkon provést. Při dvoudobém ošetření jsou k nepřímému překrytí zubní dřeně nejčastěji využívány materiály na bázi hydroxidu vápenatého a skloionomerních cementů. Kalciumfosfátové cementy mají vzhledem ke svým vlastnostem vysoký potenciál využití v této indikaci a zvýšení úspěšnosti ošetření, ale je ještě třeba udělat podrobnější in vitro výzkum a klinické studie.

Introduction, aim: Treatment of caries lesion has been for a long time one of the basic procedures in dentistry, but even today there is not completely uniform approach to this treatment in case of deep caries lesion near the dental pulp. There are three different techniques that have both advantages and disadvantages; nevertheless their common goal is to maintain the vitality of the tooth. The first approach to treatment is the total excavation of all carious tissues and a definitive filling application. The other method of treatment is the selective excavation with leaving a small area of softened dentin pulpally and application of a permanent filling. The third technique is stepwise excavation, which means two-visit treatment with gradual excavation of all carious tissues. This review article is focused on the third type of the treatment and the possibility of using various remineralization materials. Methods: For this article, studies in English were searched using key words (deep caries, stepwise excavation, indirect pulp capping, calcium hydroxide, glassionomer cement, calcium silicate cement, calcium phosphate cement) and their variations in order to summarize current knowledge about stepwise excavation method and materials used in this indication. The search was performed using PubMed, Web of Science and Cochrane Library databases and supplied by sources of Czech literature. Studies were selected mainly from journals with impact factor and published between 2010 and 2020. For the deeper understanding of the historical development of the issue, the literature was supplemented by several publications from the second half of the last century. Conclusion: The treatment of deep caries lesion with the preservation of vitality is a much discussed topic today and there is still not uniform approach, how to perform this procedure. In case of stepwise excavation, calcium hydroxide-based materials, glass ionomer cements and calcium silicate cements are usually used for indirect pulp capping. Due to their properties, calcium phosphate cements have a high potential for use in this indication and may increase the success rate of treatment, however more detailed in vitro research and clinical studies are still needed.

• Klíčová slova
• odložená exkavace,
• MeSH
• lidé MeSH
• materiály pro překrytí zubní dřeně a pulpektomii MeSH
• překrytí zubní dřeně metody   MeSH
• zubní cementy MeSH
• zubní kaz * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: The BODE (BMI, Obstruction - FEV1, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV1) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients. METHODS AND PARTICIPANTS: The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality. These were entered into the ROC analysis and reclassification analysis. Those with the strongest discriminative power were used to construct the new index (CADOT). The new index was validated on 187 patients of the CIROCO+ cohort (Netherlands; the validation cohort). RESULTS: The CADOT was constructed by adding two newly identified prognosis-determining factors, chronic heart failure (CHF) and TLCO, to the ADO index. In a head-to-head comparison, the CADOT index showed highest c-statistic values compared to the BODE and ADO indices (0.701 vs 0.677 vs 0.644, respectively). The prognostic power was more definitive when applied to the Dutch validation (CIROCO+) cohort (0.842 vs 0.799 vs 0.825, respectively). CONCLUSIONS: The CADOT index has comparable prognostic power to the BODE and ADO indices. The CADOT is complementary/an alternative to the BODE (if 6-MWT is not feasible) and ADO (with less dependence on the age factor) indices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01923051).

• MeSH
• chronická obstrukční plicní nemoc * mortalita   MeSH
• dyspnoe MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• prognóza MeSH
• respirační funkční testy MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cyclic dinucleotides (CDNs) are second messengers that bind to the stimulator of interferon genes (STING) and trigger the expression of type I interferons and proinflammatory cytokines. Here we evaluate the activity of 3',3'-c-di(2'F,2'dAMP) and its phosphorothioate analogues against five STING allelic forms in reporter-cell-based assays and rationalize our findings with X-ray crystallography and quantum mechanics/molecular mechanics calculations. We show that the presence of fluorine in the 2' position of 3',3'-c-di(2'F,2'dAMP) improves its activity not only against the wild type (WT) but also against REF and Q STING. Additionally, we describe the synthesis of the acyloxymethyl and isopropyloxycarbonyl phosphoester prodrugs of CDNs. Masking the negative charges of the CDNs results in an up to a 1000-fold improvement of the activities of the prodrugs relative to those of their parent CDNs. Finally, the uptake and intracellular cleavage of pivaloyloxymethyl prodrugs to the parent CDN is rapid, reaching a peak intracellular concentration within 2 h.

• MeSH
• estery chemie   farmakologie   terapeutické užití   MeSH
• fosfáty chemie   metabolismus   farmakologie   terapeutické užití   MeSH
• HEK293 buňky MeSH
• interferon gama metabolismus   MeSH
• krystalografie rentgenová MeSH
• leukocyty mononukleární cytologie   účinky léků   metabolismus   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• membránové proteiny agonisté   metabolismus   MeSH
• prekurzory léčiv chemická syntéza   chemie   metabolismus   farmakologie   MeSH
• teorie funkcionálu hustoty MeSH
• TNF-alfa metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Introduction: The concept of phenotyping emerged, reflecting specific clinical, pulmonary and extrapulmonary features of each particular chronic obstructive pulmonary disease (COPD) case. Our aim was to analyze prognostic utility of: "Czech" COPD phenotypes and their most frequent combinations, "Spanish" phenotypes and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages + groups in relation to long-term mortality risk. Methods: Data were extracted from the Czech Multicenter Research Database (CMRD) of COPD. Kaplan-Meier (KM) estimates (at 60 months from inclusion) were used for mortality assessment. Survival rates were calculated for the six elementary "Czech" phenotypes and their most frequent and relevant combinations, "Spanish" phenotypes, GOLD grades and groups. Statistically significant differences were tested by Log Rank test. An analysis of factors underlying mortality risk (the role of confounders) has been assessed with the use of classification and regression tree (CART) analysis. Basic factors showing significant differences between deceased and living patients were entered into the CART model. This showed six different risk groups, the differences in risk were tested by a Log Rank test. Results: The cohort (n=720) was 73.1% men, with a mean age of 66.6 years and mean FEV1 44.4% pred. KM estimates showed bronchiectases/COPD overlap (HR 1.425, p=0.045), frequent exacerbator (HR 1.58, p<0.001), cachexia (HR 2.262, p<0.001) and emphysematous (HR 1.786, p=0.015) phenotypes associated with higher mortality risk. Co-presence of multiple phenotypes in a single patient had additive effect on risk; combination of emphysema, cachexia and frequent exacerbations translated into poorest prognosis (HR 3.075; p<0.001). Of the "Spanish" phenotypes, AE CB and AE non-CB were associated with greater risk of mortality (HR 1.787 and 2.001; both p=0.001). FEV1% pred., cachexia and chronic heart failure in patient history were the major underlying factors determining mortality risk in our cohort. Conclusion: Certain phenotypes ("Czech" or "Spanish") of COPD are associated with higher risk of death. Co-presence of multiple phenotypes (emphysematous plus cachectic plus frequent exacerbator) in a single individual was associated with amplified risk of mortality.

• MeSH
• chronická bronchitida * MeSH
• chronická obstrukční plicní nemoc * diagnóza   MeSH
• fenotyp MeSH
• lidé MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Španělsko MeSH

Úvod: V současné dynamicky se rozvíjející endodoncii dochází k neustálému vývoji nových postupů ošetření a s tím souvisí i požadavky na kvalitní a spolehlivé materiály potřebné k zaplnění kořenového systému zubu. Před několika lety byly uvedeny na trh nové typy kořenových sealerů na bázi kalciumsilikátových sloučenin, které by mohly splňovat většinu parametrů dokonalého pečeticího materiálu. Novější generace těchto sealerů obsahují příměs kalciumfosfátu a jsou v zahraniční literatuře označovány jako biokeramické sealery. Cílem sdělení je objasnit problematiku této skupiny sealerů a popsat jejich chemické, fyzikální a biologické vlastnosti. Sealery na bázi biokeramických sloučenin mají mnoho společných charakteristik s původním materiálem MTA (mineral trioxide aggregate). Vynikají především hydrofilním profilem a schopností tuhnout ve vlhkém prostředí. V kontaktu s dentinem dochází na jejich povrchu k depozici precipitátů hydroxyapatitu, a tím je potencováno spolehlivé zapečetění kořenového kanálku. Z fyzikálního hlediska jsou objemově stálé a při tuhnutí byla prokázána mírná expanze. Vlhkost prostředí a vysoká afinita k vodě podporují biomineralizační pochody ve tkáních, což spolu s dobrou zatékavostí materiálu umožňuje vyplnit celý prostor kořenového kanálku včetně jeho nepravidelností. Biokompatibilita, schopnost hojení rány a nízká cytotoxicita činí tento typ sealerů vhodný pro trvalý kontakt s tkáněmi periodoncia, kde je prolongovaným uvolňováním vápenatých iontů podporována regenerace. Bylo prokázáno, že díky vysoké hodnotě pH při tuhnutí působí tyto typy sealerů rovněž antimikrobiálně. Pro klinické využití mají dostatečnou rentgen kontrastnost, avšak podle použitého radioopakního aditiva vykazují v různé míře tendenci k dys-koloracím tvrdých zubních tkání. Relativně nevýhodnou vlastností mohou rovněž být zvýšená rozpustnost, porozita a nasákavost vody. Vzhledem k dynamické a bioaktivní povaze těchto sealerů však tyto nepříznivé vlastnosti nemusí být významné pro úspěšnost ošetření v klinické praxi. Mechanické vlastnosti většiny biokeramických sealerů obecně negativně ovlivňuje aplikace tepla, proto jsou pro klinické použití doporučovány kondenzační techniky plnění kořenových kanálků za studena. Závěr: Výstupy klinických a experimentálních studií vyzdvihují výhodné vlastnosti a spolehlivost skupiny sealerů na bázi kalciumsilikátových sloučenin a naznačují do budoucna slibné výsledky při praktickém využití nejen ve specializovaných endodontických praxích.

Introduction: In modern endodontics, there is a constant development of new procedures and requirements for high-quality and reliable materials to fill the root canal system are rising. A few years ago, a new types of calcium silicate-based root canal sealers were launched on the market, which could meet most of the parameters of a perfect sealing material. Newer generations of these sealers contain calcium phosphate and are also referred to in the literature worldwide as bioceramic sealers. Aim of the article: The aim of this article is to present the characteristics of this group of sealers and to outline their chemical, physical and biological properties. Bioceramicbased root canal sealers have many characteristics in common with the original material MTA (mineral trioxide aggregate). They are similar to its chemical composition and setting reaction. They are hydrophilic and able to set in humid environments. In contact with the dentin, hydroxyapatite crystals are deposited on the surface, thus enhancing the sealing ability of the root canal. Considering their physical characteristics, they are volumetrically stable and there is even a slight expansion during material setting. Humidity of the environment and high water sorption promote the biomineralization processes, and contribute to a better seal of the root canal. The flowability of the material allows to fill the entire space of the root canal, even including its irregularities. Biocompatibility, wound healing ability and minimal cytotoxicity make this type of sealer suitable for permanent contact with periodontal tissues, where prolonged release of calcium ions promotes regeneration. High pH value during material setting result in an antimicrobial effect. They have sufficient X-ray contrast for clinical use, but depending on the radiopaque additive used, they show a tendency to discoloration of hard dental tissues. A relatively disadvantageous features are increased solubility, porosity and water absorption. However, due to the dynamic and bioactive nature of these sealers, these adverse properties may not be significant for the success of treatment in clinical practice. The mechanical properties of most bioceramic sealers are generally negatively affected by heat. Due to this fact, cold obturation methods are recommended for bioceramic-based sealers. Conclusion: The outcomes of clinical and experimental studies generally highlight the beneficial properties and reliability of this group of sealers. They suggest promising results not only in specialized endodontic practices.

• Klíčová slova
• biokeramický sealer, kalciumsilikátový sealer,
• MeSH
• lidé MeSH
• výplňové materiály kořenových kanálků * MeSH
• zubní porcelán MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH