BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.
BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.
- MeSH
- difuzní intrinsický pontinní gliom genetika diagnóza krev MeSH
- dítě MeSH
- epigeneze genetická MeSH
- gliom genetika diagnóza krev patologie diagnostické zobrazování MeSH
- histony * genetika metabolismus krev MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- nádorové biomarkery krev MeSH
- nádory mozkového kmene genetika diagnóza krev diagnostické zobrazování patologie metabolismus MeSH
- předškolní dítě MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The actions required to achieve higher-quality and harmonised global surveillance of child and adolescent movement behaviours (physical activity, sedentary behaviour including screen time, sleep) are unclear. OBJECTIVE: To identify how to improve surveillance of movement behaviours, from the perspective of experts. METHODS: This Delphi Study involved 62 experts from the SUNRISE International Study of Movement Behaviours in the Early Years and Active Healthy Kids Global Alliance (AHKGA). Two survey rounds were used, with items categorised under: (1) funding, (2) capacity building, (3) methods, and (4) other issues (e.g., policymaker awareness of relevant WHO Guidelines and Strategies). Expert participants ranked 40 items on a five-point Likert scale from 'extremely' to 'not at all' important. Consensus was defined as > 70% rating of 'extremely' or 'very' important. RESULTS: We received 62 responses to round 1 of the survey and 59 to round 2. There was consensus for most items. The two highest rated round 2 items in each category were the following; for funding (1) it was greater funding for surveillance and public funding of surveillance; for capacity building (2) it was increased human capacity for surveillance (e.g. knowledge, skills) and regional or global partnerships to support national surveillance; for methods (3) it was standard protocols for surveillance measures and improved measurement method for screen time; and for other issues (4) it was greater awareness of physical activity guidelines and strategies from WHO and greater awareness of the importance of surveillance for NCD prevention. We generally found no significant differences in priorities between low-middle-income (n = 29) and high-income countries (n = 30) or between SUNRISE (n = 20), AHKGA (n = 26) or both (n = 13) initiatives. There was a lack of agreement on using private funding for surveillance or surveillance research. CONCLUSIONS: This study provides a prioritised and international consensus list of actions required to improve surveillance of movement behaviours in children and adolescents globally.
- MeSH
- budování kapacit MeSH
- čas strávený před obrazovkou * MeSH
- celosvětové zdraví MeSH
- cvičení * MeSH
- delfská metoda * MeSH
- dítě MeSH
- konsensus MeSH
- lidé MeSH
- mladiství MeSH
- sedavý životní styl * MeSH
- spánek MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Smoking is an important risk factor leading to many diseases, which brings substantial healthcare costs as well as indirect costs due to decreased productivity. This article aims to quantify the social costs of smoking in the Czech Republic in 2019. METHODS: The prevalence-based, cost-of-illness approach is used, which assesses the costs as the sum of direct (healthcare) costs and indirect costs (productivity losses due to mortality and morbidity). The costs of healthcare utilization and pharmacotherapy in direct costs, and the costs of absenteeism, presenteeism, and premature mortality in indirect costs, are included. RESULTS: Total costs of smoking in the Czech Republic in 2019 are estimated as 2110.6 million EUR (0.94% of GDP). Direct costs amounted to 537.0 million EUR (2.9% of health expenditures in 2019) and indirect costs were 1573.6 million EUR, mainly driven by the costs of premature mortality (1062.5 million EUR). CONCLUSIONS: Despite the declining trend in the prevalence of smoking in the Czech Republic, the associated costs are considerable. Investments into strategies to reduce smoking continue to be needed.
- MeSH
- absentérství MeSH
- dospělí MeSH
- kouření * ekonomika epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- náklady na zdravotní péči * statistika a číselné údaje MeSH
- osobní újma zaviněná nemocí * MeSH
- předčasná smrt MeSH
- prevalence MeSH
- senioři MeSH
- výdaje na zdravotnictví statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Natural killer (NK) cell-based therapies represent a promising approach for acute myeloid leukemia (AML) relapse, yet their efficacy is hindered by immunosuppressive factors such as transforming growth factor beta (TGF-β) in the tumor microenvironment. This study investigated the effects of TGF-β on NK cell cytotoxicity and migration using 2D and 3D co-culture models that mimic the leukemic microenvironment. METHODS: TGF-β production was evaluated in AML-derived leukemic cell lines and mesenchymal stromal cells (hTERT-MSCs) using ELISA. Bulk RNA sequencing (RNA-seq) was performed to analyze global gene expression changes in TGF-β-treated primary human NK cells. NK cell cytotoxicity and migration were assessed in 2D monolayer and 3D spheroid co-cultures containing hTERT-MSCs and leukemic cells using flow cytometry and confocal microscopy. RESULTS: Both leukemic cells and MSCs produced TGF-β, with increased levels observed in MSCs after co-culture with primary AML blasts. RNA sequencing revealed that TGF-β altered key gene pathways associated with NK cell cytotoxicity, adhesion, and migration, supporting its immunosuppressive role. In functional assays, TGF-β exposure significantly reduced NK cell-mediated cytotoxicity in a time-dependent manner and impaired NK cell infiltration into 3D spheroids, particularly in models incorporating MSCs. Additionally, MSCs themselves provided a protective environment for leukemic cells, further reducing NK cell effectiveness in 2D co-cultures. CONCLUSION: TGF-β suppresses both NK cell cytotoxicity and migration, limiting their ability to eliminate leukemic cells and infiltrate the bone marrow niche (BMN). These findings provide novel insights into TGF-β-mediated immune evasion mechanisms and provide important insights for the future design of NK-based immunotherapies and clinical trials.
- Publikační typ
- časopisecké články MeSH
Stem cell-based therapy represents a promising approach for the treatment of numerous currently uncurable diseases. However, wider application of this therapy is still bound by various limitations. To increase the effectiveness of cell therapy, a combined application of stem cells with various types of chemicals or agents, which could support the immunoregulatory and therapeutic properties of stem cells, has been proposed and tested. One prospective approach is offered by the co-application of mesenchymal stem cells (MSCs), which have potent immunomodulatory and regenerative properties, and selected metal nanoparticles (NPs) which have been used in various fields of medicine for their immunomodulatory, anti-oxidant and antibacterial properties. It has been shown that the main mechanism of the therapeutic action of MSCs is the production of immunomodulatory molecules and growth factors, and that the secretory activity of MSCs can be modified by different types of NPs. For this purpose, metal NPs are extremely useful. They possess unique characteristics and can influence the growth and repair of tissues, exert strong antimicrobial activity and serve as nanocarriers. Thus, treatment based on the simultaneous application of MSCs and selected NPs combines the therapeutic effects of MSCs and impacts of NPs on applied MSCs, and on the cells and tissues of the recipient. In this review we outline the current state of studies combining the administration of MSCs and the application of metal NPs, with a focus on perspectives to use such treatment for corneal and retinal injuries and diseases.
- MeSH
- kombinovaná terapie metody MeSH
- kovové nanočástice * chemie terapeutické užití MeSH
- lidé MeSH
- mezenchymální kmenové buňky * cytologie MeSH
- oční nemoci * terapie MeSH
- transplantace mezenchymálních kmenových buněk * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: We designed and validated a concise, efficient screening tool, the Sleep Apnea Risk Assessment (SARA), to identify patients at high risk of moderate to-severe obstructive sleep apnea. PATIENTS AND METHODS: We conducted a two-phase, multicenter study from September 1, 2018, to October 31, 2023. We created Cohort A (n=221, mean age 50.5±13.0 years, 69.2% male) to design SARA and compared the results with the Epworth Sleepiness Scale, Berlin Questionnaire, Pittsburgh Sleep Quality Index, STOP-Bang, and STOP questionnaires. Cohort B (n=253, mean age 48.0±13.4 years, 75.5% male) served for validation. RESULTS: SARA comprises six variables with the highest accuracy: sleep apnea observed by the bedroom partner (8 points), snoring (5 points), male sex (3 points), age≥50 years (3 points), daytime fatigue (3 points), and body mass index≥30 kg/m2 (2 points). SARA yielded an area under the receiver operating characteristic curve (AUC) of 0.77 (95% CI: 0.71-0.83) and sensitivity of 87.2% (95% CI: 80.8-92.1) in cohort A at a cut-off score of ≥11 points. Validation in cohort B showed an AUC of 0.79 (95% CI: 0.74-0.84) and a sensitivity of 98% (95% CI: 89.2-95.4). SARA performance significantly outperformed the other questionnaires tested. CONCLUSION: The SARA is a promising new screening tool for moderate-to-severe obstructive sleep apnea, demonstrating high sensitivity and a strong ROC curve. Further large-scale validation is recommended.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The immunosuppressive roles of galectin-3 (Gal-3) in carcinogenesis make this lectin an attractive target for pharmacological inhibition in immunotherapy. Although current clinical immunotherapies appear promising in the treatment of solid tumors, their efficacy is significantly weakened by the hostile immunosuppressive tumor microenvironment (TME). Gal-3, a prominent TME modulator, efficiently subverts the elimination of cancer, either directly by inducing apoptosis of immune cells or indirectly by binding essential effector molecules, such as interferon-gamma (IFNγ). METHODS: N-(2-Hydroxypropyl)methacrylamide (HPMA)-based glycopolymers bearing poly-N-acetyllactosamine-derived tetrasaccharide ligands of Gal-3 were designed, synthesized, and characterized using high-performance liquid chromatography, dynamic light scattering, UV-Vis spectrophotometry, gel permeation chromatography, nuclear magnetic resonance, high-resolution mass spectrometry and CCK-8 assay for evaluation of glycopolymer non-toxicity. Pro-immunogenic effects of purified glycopolymers were tested by apoptotic assay using flow cytometry, competitive ELISA, and in vitro cell-free INFγ-based assay. RESULTS: All tested glycopolymers completely inhibited Gal-3-induced apoptosis of monocytes/macrophages, of which the M1 subtype is responsible for eliminating cancer cells during immunotherapy. Moreover, the glycopolymers suppressed Gal-3-induced capture of glycosylated IFNγ by competitive inhibition to Gal-3 carbohydrate recognition domain (CRD), which enables further inherent biological activities of this effector, such as differentiation of monocytes into M1 macrophages and repolarization of M2-macrophages to the M1 state. CONCLUSION: The prepared glycopolymers are promising inhibitors of Gal-3 and may serve as important supportive anti-cancer nanosystems enabling the infiltration of proinflammatory macrophages and the reprogramming of unwanted M2 macrophages into the M1 subtype.
- MeSH
- akrylamidy chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- galektin 3 * antagonisté a inhibitory MeSH
- galektiny MeSH
- interferon gama * metabolismus MeSH
- krevní proteiny MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- monocyty * účinky léků MeSH
- nádorové mikroprostředí účinky léků MeSH
- polymery * chemie farmakologie MeSH
- protinádorové látky * farmakologie chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
During the COVID-19 pandemic, specific COVID-19-related conditions renewed interest in the full-awake venovenous extracorporeal membrane oxygenation ( fa V-V ECMO) approach, in which ECMO is applied to awake, cooperative, and non-intubated patients. This scoping review aims to provide a descriptive overview of fa V-V ECMO in patients with COVID-19-related acute respiratory distress syndrome (CARDS). We searched the PubMed, Web of Science, and Scopus databases using the keywords "awake ECMO" or "spontaneous breathing AND ECMO", combined with "COVID-19", "SARS-CoV-2" or "coronavirus", utilizing the Boolean operator "AND". The search included papers published from November 1, 2019, to December 31, 2024. Sixty-four papers were assessed for eligibility at the abstract level, and fourteen articles (seven small-sample cohort studies and seven case reports) comprising 95 patients were included in the final analysis. The most frequent reasons for preferring fa V-V ECMO over mechanical ventilation were barotrauma and patient refusal of intubation and mechanical ventilation. The fa V-V ECMO strategy was successful (ie, patients not intubated, disconnected from ECMO, and discharged from the hospital) in 36.4% of cases (cohort studies only). The incidence of defined severe adverse events (bleeding, thrombosis, cannula malposition, delirium, and progression of barotrauma) was considered low. The mortality rate for CARDS patients treated with fa V-V ECMO (including only patients from cohort studies) reached 33.0%, notably lower than the 48% reported for CARDS patients treated with V-V ECMO in the ELSO registry. Patients who were intubated due to worsening respiratory failure during fa V-V ECMO had significantly higher mortality. Infectious complications, sepsis, and multiorgan failure were the most frequent causes of death. However, significant heterogeneity in the definitions and reporting of management, ECMO-related complications, and outcomes was observed across the papers. Despite the heterogeneity of the data, fa V-V ECMO in CARDS patients can be considered a safe approach associated with a lower mortality rate than that reported in the overall V-V ECMO CARDS population.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
