The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry-Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.
Euglenids have long been studied due to their unique physiology and versatile metabolism, providing underpinnings for much of our understanding of photosynthesis and biochemistry, and a growing opportunity in biotechnology. Until recently there has been a lack of genetic studies due to their large and complex genomes, but recently new technologies have begun to unveil their genetic capabilities. Whilst much research has focused on the model organism Euglena gracilis, other members of the euglenids have now started to receive due attention. Currently only poor nuclear genome assemblies of E. gracilis and Rhabdomonas costata are available, but there are many more plastid genome sequences and an increasing number of transcriptomes. As more assemblies become available, there are great opportunities to understand the fundamental biology of these organisms and to exploit them for biotechnology.
Aim: Research on the health consequences of violent victimization of people with disabilities is lacking. This study aims to identify the factors that are associated with physical and mental health impacts of anti-disability bias victimization. Methods: The study drew on a unique sample of 331 self-identified people with disabilities, all over the age of 15, residing in Czechia. From this sample, 47 questionnaires were excluded. The respondents were asked about the most serious incident of anti-disability bias victimization in the last five years. A series of bivariate binary logistic regressions were performed - with the consequences of this incident as outcomes (mental health and physical health). Results: 90 respondents (32%) reported experiencing the most serious incident of bias victimization in the last five years. 60% of victims reported anxiety and sadness, and 28% deterioration in physical health. The results suggest that victims experience physical and mental health consequences unequally. Age, perceived disability in specific areas, visibility of disability, presence of multiple disabilities, and number of offenders are associated with the experience of physical health deterioration. Education, perceived disability in specific areas, and visibility of disability are associated with the experience of mental health impacts. Conclusion: Certain groups of people with disabilities who experience victimization report poorer physical and mental health outcomes. This differential experience should be considered in immediate responses and prevention programs.
- MeSH
- Mental Health statistics & numerical data MeSH
- Emotions MeSH
- Humans MeSH
- Logistic Models MeSH
- Violence psychology statistics & numerical data MeSH
- Persons with Disabilities * psychology statistics & numerical data MeSH
- Prejudice * psychology statistics & numerical data MeSH
- Social Problems psychology statistics & numerical data MeSH
- Health statistics & numerical data MeSH
- Self Report MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Immune checkpoints are critical in modulating immune responses and maintaining self-tolerance. Cancer cells can exploit these mechanisms to evade immune detection, making immune checkpoints attractive targets for cancer therapy. The introduction of immune checkpoint inhibitors (ICIs) has transformed cancer treatment, with monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1 demonstrating clinical success. However, challenges such as immune-related adverse events, primary and acquired resistance, and high treatment costs persist. To address these challenges, it is essential to explore alternative strategies, including small-molecule and peptide-based inhibitors, aptamers, RNA-based therapies, gene-editing technologies, bispecific and multispecific agents, and cell-based therapies. Additionally, innovative approaches such as lysosome-targeting chimeras, proteolysis-targeting chimeras, and N-(2-hydroxypropyl) methacrylamide copolymers are emerging as promising options for enhancing treatment effectiveness. This review highlights significant advancements in the field, focusing on their clinical implications and successes.
Vydání první 274 stran : ilustrace, portréty ; 21 cm
Publikace obsahuje osobní vyprávění autora i jeho pacientů o zdraví, nemocech a společenských tématech Určeno široké veřejnosti.; Jan Hnízdil i tentokrát přichází s knihou, která svědčí o mimořádné šíři jeho záběru. V tematicky nesourodých kapitolách poutavě řeší nejen příběhy svých pacientů, lásku ke zvířatům, ale i příběhy svého života a otázky celé společnosti. Síla příběhů spočívá v tom, že na jednotlivých situacích ukazuje, že i v dnešní době se lze složitostem života postavit autonomně, bez přetvářky, a hlavně s velmi originálním humorem. S Janem Hnízdilem nemusí každý souhlasit, ale nemůže mu upřít poctivou snahu o otevřenost bez dogmat, hledání odpovědí na komplikované otázky a víru v mezilidské porozumění a přátelství. MUDr. Jan Hnízdil, internista a rehabilitační lékař (*1958), autor publikací: Mým marodům, Zaříkávač nemocí, Příběhy obyčejného uzdravení, Ako sa nestať pacientom, O bolesti zad: Všechno, co jste kdy chtěli vědět, ale báli jste se zeptat, Všichni jsou psychopati jenom já jsem letadlo, Kronika doby covidové a dalších. V roce 2013 založil pracoviště komplexní psychosomatické medicíny Hnízdo zdraví, o které v roce 2024 přišel. Je držitelem Zlatého bludného balvanu Klubu českých skeptiků Sisyfos za rok 2015. Pro hrubé porušení lékařské odbornosti a etiky v době covidizmu vyloučil v roce 2024 Českou lékařskou komoru ze svojí společnosti a přešel na pozici zdravotního poradce.
- MeSH
- History, 21st Century MeSH
- Patients MeSH
- Attitude MeSH
- Psychosomatic Medicine MeSH
- Social Problems MeSH
- Health MeSH
- Check Tag
- History, 21st Century MeSH
- Publication type
- Personal Narrative MeSH
- Geographicals
- Czech Republic MeSH
- Conspectus
- Fyzioterapie. Psychoterapie. Alternativní lékařství
- Biografie
- NML Fields
- psychologie, klinická psychologie
- rehabilitační a fyzikální medicína
- About
- Hnízdil, Jan, 1958- Authority
Vydání první 221 stran : ilustrace ; 21 cm
Publikace obsahuje osobní vyprávění lidí, které nějakým způsobem zasáhla sebevražda, a také je příručkou prevence sociálních problémů a sebevražd mladistvých. Určeno široké veřejnosti.
Many tasks in forensic examination of handwritten documents require classification of writing instruments that have ink of similar properties as the ink found on a questioned document. In this paper, we propose a new methodology for non-destructive identification of inks based on optical properties and reflectance spectra of the ink, measured from handwriting strokes. Building on this methodology, we developed an interactive database that we call the "Pen Ink Library", which lists 718 various writing instruments and enables systematic comparison and semi-automatic search of writing instruments, using the measured characteristics of their ink. To highlight the significance and applicability of the database, we additionally exploit the large amounts of collected measurements to design computer-based data analysis methods for classification and comparative analysis of ink samples. For validation of the semi-automatic search functionality of the Pen Ink Library we performed a series of blind tests using twenty randomly selected writing instruments. Here, an instrument with the same brand and model was found in nine cases, and an instrument with a different brand and model, but with identical spectrum and optical parameters, was found in five cases. Cross-validation of the computer-based data analysis methods on the measurements from the database yielded above 90% accuracy of the classification method and 5.3% to 12.7% error rate of the comparative analysis method.
- Publication type
- Journal Article MeSH
Genomic alterations and enormous monoclonal immunoglobulin production cause multiple myeloma to heavily depend on proteostasis mechanisms, including protein folding and degradation. These findings support the use of proteasome inhibitors for treating multiple myeloma and mantle cell lymphoma. Myeloma treatment has evolved, especially with the availability of new drugs, such as proteasome inhibitors, into therapeutic strategies for both frontline and relapsed/refractory disease settings. However, proteasome inhibitors are generally not effective enough to cure most patients. Natural resistance and eventual acquired resistance led to relapsed/refractory disease and poor prognosis. Advances in the understanding of cellular proteostasis and the development of innovative drugs that also target other proteostasis network components offer opportunities to exploit the intrinsic vulnerability of myeloma cells. This review outlines recent findings on the molecular mechanisms regulating cellular proteostasis pathways, as well as resistance, sensitivity, and escape strategies developed against proteasome inhibitors and provides a rationale and examples for novel combinations of proteasome inhibitors with FDA-approved drugs and investigational drugs targeting the NRF1 (NFE2L1)-mediated proteasome bounce-back response, redox homeostasis, heat shock response, unfolding protein response, autophagy, and VCP/p97 to increase proteotoxic stress, which can improve the efficacy of antimyeloma therapy based on proteasome inhibitors.
- MeSH
- Drug Resistance, Neoplasm MeSH
- Proteostasis * drug effects MeSH
- Proteasome Inhibitors * therapeutic use pharmacology MeSH
- Humans MeSH
- Multiple Myeloma * drug therapy metabolism MeSH
- Antineoplastic Agents * therapeutic use pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Niche partitioning allows species to diversify resource utilisation and space allocation and reduce interspecific competition. Variations in abiotic and biotic conditions in different ecosystems may further influence resource availability and habitat utilisation, potentially reducing competition. The aim of this study is to investigate the effects of environmental variation on spatial and trophic niche overlap between two freshwater apex predators, the northern pike (Esox lucius) and the European catfish (Silurus glanis), in three different water bodies. METHODS: We used fine-scale acoustic telemetry to assess the spatial niche overlap of pike and catfish, analyzing their spatial and habitat use in relation to the thermocline and their presence in benthic versus open-water habitats. Stable isotope analysis (SIA) was used to quantify trophic niche overlap and dietary differences between the species. We compared the habitat use, spatial niche width and overlap, and trophic differentiation among waterbodies to determine how environmental conditions influence predator interactions. RESULTS: During summer, pike and catfish primarily occupied benthic habitats above the thermocline across all waterbodies and diel periods. However, catfish more frequently used open water above the thermocline, while pike were more often present in both open water and benthic habitats below it. While this general pattern of habitat use was consistent, its extent varied among lakes, suggesting that local environmental conditions shape species-specific habitat selection. Despite these variations, the species exhibited substantial spatial overlap, though its magnitude fluctuated across waterbodies and diel periods. Catfish occupied a broader spatial niche in two waterbodies, while pike had a broader niche in one. Across all lakes, catfish consistently maintained a broader trophic niche than pike. However, pike exhibited higher trophic overlap with catfish than vice versa, with nearly complete overlap in one lake and substantial but incomplete overlap in others. This suggests that pike relies more heavily on shared prey resources, while catfish exploits a broader range of food sources beyond those used by pike.These patterns were primarily driven by the position of the thermocline, prey availability, structural complexity and the greater foraging plasticity of catfish, highlighting the environmental dependence of niche partitioning in these predators. CONCLUSIONS: Our findings demonstrate that spatial and trophic niche overlaps between pike and catfish are highly context-dependent, shaped by abiotic conditions, prey availability, and species-specific foraging strategies. This study highlights the importance of integrating spatial and trophic analyses to understand predator interactions in aquatic ecosystems.
- Publication type
- Journal Article MeSH
Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability to target solid tumors, penetrate the tumor microenvironment (TME), and act as efficient drug delivery platforms highlights their potential in nanomedicine. However, the complex and dynamic nature of the TME, characterized by metabolic heterogeneity, immune suppression, and drug resistance, poses significant challenges to effective cancer treatment. GBMs offer innovative solutions by enhancing tumor targeting, facilitating deep tissue penetration, and modulating metabolic pathways that contribute to tumor progression and immune evasion. Their functionalization with targeting ligands and biocompatible polymers improves their biosafety and specificity, while their ability to modulate immune cell interactions within the TME presents new opportunities for immunotherapy. Given the role of metabolic reprogramming in tumor survival and resistance, GBMs could be further exploited in metabolism-targeted therapies by disrupting glycolysis, mitochondrial respiration, and lipid metabolism to counteract the immunosuppressive effects of the TME. This review focuses on discussing research studies that design GBM nanocomposites with enhanced biodegradability, minimized toxicity, and improved efficacy in delivering therapeutic agents with the intention to reprogram the TME for effective anticancer therapy. Additionally, exploring the potential of GBM nanocomposites in combination with immunotherapies and metabolism-targeted treatments could lead to more effective and personalized cancer therapies. By addressing these challenges, GBMs could play a pivotal role in overcoming current limitations in cancer treatment and advancing precision oncology.
- MeSH
- Graphite * chemistry therapeutic use MeSH
- Immunotherapy methods MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Tumor Microenvironment * drug effects MeSH
- Neoplasms * drug therapy metabolism MeSH
- Nanocomposites * chemistry therapeutic use MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
