PURPOSE: Evaluate whether optic disc edema results in changes in retinal microcirculation. PATIENTS AND METHODS: The study group consisted of 11 patients with unilateral optic disc edema (papilledema). The control group consisted of the healthy eyes of the same 11 patients. Patients underwent non-invasive photo-spectrometric retinal oximetry using Oxymap T1 retinal oximeter (Oxymap, Reykjavik, Iceland). In the eyes of these 11 patients, we examined the diameter of the retinal arteries and veins, arterial and venous blood oxygen saturation, and the difference in oxygen saturation between arterioles and venules (A-V difference). RESULTS: In the papilledema group, the decrease in the retinal arterial diameter was statistically significant (p=0.001). The median diameter of the retinal artery was 11.70 px (IQR 1.47) or after conversion 109.00 µm (IQR 14.00) in the papilledema group and 13.75 px (IQR 1.61) or 128.00 µm (IQR 15.00) in the control group. The increase in the diameter of the retinal veins in the papilledema group was statistically significant (p=0.012), where the median diameter in the papilledema group was 20.88 px (IQR 3.72) or 194.00 µm (IQR 35.00), and in the control group was 18.18 px (IQR 3.60) or 169 µm (IQR 33.00). There was a statistically significant decrease (p<0.001) in the venous saturation in the papilledema group with a median value of 53.16% (IQR 17.38) and 60.02% (IQR 11.98) in the control group. The median of the A-V difference was 51.92 (IQR 15.96) in the papilledema group, resp. 38.49 (IQR 9.75) in the control group and a significant increase in the papilledema group (p<0.001) was reported. CONCLUSION: Automatic retinal oximetry demonstrated changes in the retinal microcirculation in patients with optic disc edema.
- Klíčová slova
- microcirculation, oximetry, papilledema, retina,
- Publikační typ
- časopisecké články MeSH
PURPOSE: Aspartate β-hydroxylase (ASPH) contributes to carcinogenesis by promoting tumor cell proliferation, migration, and invasion. The enzymatic activity of ASPH can be inhibited by small molecule inhibitors that have been shown to have anti-metastatic activity in rodent models. ASPH has also been shown to inhibit the activation of natural killer (NK) cells. Therefore, this study aimed to investigate the effect of ASPH inhibition on the induction of anti-tumor immunity and to analyze the immune cells involved. METHODS: In the mouse TC-1/A9 model characterized by reversible downregulation of major histocompatibility class I (MHC-I) molecules, ASPH inhibition was combined with stimulation of innate and/or adaptive immunity, and the anti-tumor response was analyzed by evaluation of tumor growth, in vivo depletion of immune cell subpopulations, and ELISPOT assay. Characteristics of immune cells in the spleen and tumor were determined by flow cytometry and single-cell RNA sequencing (scRNA-seq). RESULTS: ASPH inhibition did not reduce tumor growth or promote the anti-tumor effect of innate immunity stimulation with the synthetic oligonucleotide ODN1826, but it significantly enhanced tumor growth reduction induced by DNA vaccination. In vivo immune cell depletion suggested that CD8+ T cells played a critical role in this immunity stimulated by combined treatment with ASPH inhibition and DNA vaccination. ASPH inhibition also significantly enhanced the specific response of CD8+ T cells induced by DNA vaccination in splenocytes, as detected by ELISPOT assay, and reduced the number of regulatory T cells in tumors. scRNA-seq confirmed the improved activation of CD8+ T cells in tumor-infiltrating cells after combined therapy with DNA vaccination and ASPH inhibition. It also showed activation of NK cells, macrophages, and dendritic cells in tumors. CONCLUSION: ASPH inhibition stimulated T-cell-mediated adaptive immunity induced by DNA vaccination. Different types of lymphoid and myeloid cells were likely involved in the activated immune response that was efficient against tumors with MHC-I downregulation, which are often resistant to T-cell-based therapies. Due to different types of activated immune cells, ASPH inhibition could improve immunotherapy for tumors with various MHC-I expression levels.
- Klíčová slova
- ASPH, adaptive immunity, cancer immunotherapy, scRNA-seq, tumor microenvironment,
- Publikační typ
- časopisecké články MeSH
Partnerships between patients and the medical research community are strengthening. Patient involvement in research processes through collaborative workstreams provides authentic insights and perspectives, enhances trust between stakeholders and the patient community, brings balance to authorship groups and adds value and contextualisation to publications. Here, patient advocates, representatives from patient and caregiver communities and pharmaceutical and medical communications professionals propose seven actions to advance patient authorship and collaboration in peer-reviewed publications. Drawing on research, personal experience and professional insight, they call for a shift in conventional publication development practices-from seeking reasons to include patient authors to requiring justification for their exclusion-thereby facilitating greater inclusion and representation of the patient voice. The authors advocate moving beyond the concept of 'patient-centricity' towards 'patient partnership' to reflect a collaborative approach and more equitable balance of power and benefits among stakeholders. They also emphasise the importance of involving patients holistically in publication steering committees to ensure that the publication landscape includes patient perspectives and represents lived experiences. Continued facilitation and strengthening of partnerships between patient and non-patient authors is noted as essential for improving communication, understanding and equity within authorship groups. To support the visibility and recognition of patient authors, they recommend the use of the 'patient author' affiliation metatag to better identify, search, filter and standardise publications with patient involvement, identify patient authors and help build an evidence base from which best practice and guidance can be developed. Additionally, the authors highlight the need to consider and develop guidance around compensation of patient authors to acknowledge the contribution and time commitments across the research process and enable greater diversity, equity and inclusion. Finally, they stress the importance of extending the reach of publications to wider audiences through enhanced accessibility formats and open access.
‘Patients’ are often described in a general way as people who live with or are affected by disease, either as patients or carers of patients. The companies that research and create medicines (pharmaceutical companies) are working more and more with patients. This helps pharmaceutical companies to better understand patients’ experiences of disease, unmet needs and views on treatment and care. If patients are involved in evidence generation, they should also be able to provide input in any subsequent published research to enhance the value of the publications. Patient involvement ensures that opinions and experiences are gathered directly from the patients, rather than from other people on their behalf. Patient involvement can help to bridge the gap between researchers, pharmaceutical companies and the people for whom the medicine is actually developed.Publications co-authored by patients may also help doctors and other healthcare professionals understand what is important to patients, supporting shared-decision-making and patient–doctor communication. Patient authorship enhances diversity, equity and inclusion in medical publishing. In this paper, patient representatives and people who have experience of evidence generation and delivering or contributing to scientific publications discuss how and why patients should be involved as authors (and reviewers) of peer-reviewed research papers. Please see the graphical abstract for our key summary points, which we propose to the readers and writers of research papers.
- Publikační typ
- časopisecké články MeSH
- přehledy 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.
- Klíčová slova
- 3D models, NK cells, TGFbeta, acute myeloid leukemia, bone marrow niche, immunotherapy,
- 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.
- Klíčová slova
- combined application, mesenchymal stem cells, metal nanoparticles, ocular disorders, therapeutic effect,
- 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
INTRODUCTION: Medicinal plants are extensively utilized as dietary supplements to encourage disease prevention and to support the treatment of various health disorders. Unfortunately, several plants are known for mycotoxin contamination, which may overwhelm any beneficial effects the plants might have. OBJECTIVE: The purpose of the study was to determine the presence of ochratoxin A (OTA) and citrinin (CIT) in medicinal herbal products (MHP). METHODS: Sixty samples of different MHP types were purchased on the Czech market during 2020-2021. Both mycotoxins were determined using high-performance liquid chromatography with a fluorescence detector with immunoaffinity columns employed as a pretreatment. RESULTS: In total, 40% and 27% of samples were above the limit of quantification with the concentrations ranging up to 826.62 ng/g and 472.79 ng/g for OTA and CIT, respectively. The co-occurrence was confirmed in six MHP types. CONCLUSIONS: MHP could be a significant source of OTA and CIT. To protect the health of MHP users, it is desirable to continue monitoring the presence of mycotoxins in MHP. During this study, new OTA regulations for herbs came into force in the EU.
- Publikační typ
- časopisecké články 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.
- Klíčová slova
- Berlin questionnaire, Epworth sleepiness scale, SARA, STOP-bang, obstructive sleep apnea, screening questionnaire,
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: This study explores the impact of two major labor market phenomena-the aging workforce and digitalization, which have global significance. The COVID-19 pandemic accelerated the adoption of digital technologies, resulting in economic growth, improved business processes, and reduced social isolation. However, the study also addresses the challenges and threats associated with digitalization, with a specific focus on technostress. The research analyses the primary techno-stressors experienced by older employees and self-employed individuals in four EU countries. Investigating various demographic factors such as gender, age, education level, employment type, and country of origin, the study aims to identify stress levels related to techno-demands and techno-disruption. METHODS: This study utilized a quantitative research design with a cross-sectional survey approach. A Quota sampling method in combination with Computer Assisted Web Interviewing (CAWI) was used to collect data. The overall response rate was 42% (varied by country) in total data collected. A sample of 1306 workers (aged 50-64), representing diverse demographics, was recruited and interviewed. The techno-stressors were assessed using a 14-item scale encompassing major stress-creating conditions as already reported in earlier studies. RESULTS: The results reveal intriguing patterns, particularly notable gender-based differences in technostress experiences across age groups. Younger male seniors and female seniors reported higher levels of techno-disruption, while techno-demands were more problematic for female seniors. Additionally, respondents' country of origin also influenced their experiences with technostress. DISCUSSION: Overall, the study sheds light on the challenges of digitalization for older workers in central European perspective and provides important missing information and data on variation in technostress based on nationality, age, and gender. The results prompt further research on longitudinal trends and discussions on geography, industry, and country specific impact of digitalization on the modern workforce.
- Klíčová slova
- Central Europe, age, gender, older workers, technostress, technostressors,
- 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.
- Klíčová slova
- carbohydrate, galectin-3, glycopolymer, interferon-gamma, monocyte, tumor microenvironment,
- 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
- Názvy látek
- akrylamidy MeSH
- galektin 3 * MeSH
- galektiny MeSH
- interferon gama * MeSH
- krevní proteiny MeSH
- LGALS3 protein, human MeSH Prohlížeč
- polymery * MeSH
- protinádorové látky * 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.
