Extracellular vesicles (EVs) are a heterogeneous population of membrane-bound particles that mediate intercellular communication through the horizontal transfer of biologically active cargo, including microRNAs (miRNAs). Although numerous miRNAs have been identified in EVs, it remains unclear which miRNAs are selectively enriched and how they contribute to EV-mediated biological effects in recipient cells. Using colorectal cancer (CRC) as a model system, we investigated the selective enrichment of EV-associated miR-1290 and explored its potential biological relevance. EVs were isolated from CRC cell lines and patients' plasma by ultracentrifugation and characterized according to current guidelines. Small RNA sequencing of CRC cells and their EVs revealed selective enrichment of miR-1290 in CRC-derived EVs, which was validated by RT-qPCR. Sequence analysis of miR-1290 revealed the putative AGGG EXOmotif in the canonical sequence and most detected isomiR variants, including the most abundant isomiR, while the GGAG EXOmotif, previously implicated in miRNA sorting into EVs, was present in the most abundant isomiR and several additional isomiR variants. Transfer experiments demonstrated that CRC-derived EVs efficiently deliver miR-1290 to parental cancer cells in an auto-/paracrine manner. CRC-EV uptake modulated the expression of the predicted miR-1290 target genes FGF2 and EPCAM, as assessed by RT-qPCR, ELISA, and flow cytometry; however, the observed effects were not solely attributable to miR-1290, suggesting a contribution of additional EV cargo components. In plasma samples from CRC patients and healthy donors, miR-1290 was detected in both plasma-derived EVs and the EV-depleted plasma fraction, with slightly higher levels observed in CRC patients. Together, these findings show that miR-1290 is selectively enriched in CRC-derived EVs and transferred to recipient cells. The presence of conserved EXOmotifs supports the possible involvement of selective EV-sorting mechanisms, while the biological effects of CRC-derived EVs likely reflect the combined effects of multiple cargo components. Detection of miR-1290 in circulating EVs further highlights its potential as a complementary biomarker candidate in CRC.
Following the new ESPEN Standard Operating Procedures, the previous 2019 guideline to provide best medical nutritional therapy to critically ill patients has been shortened and partially revised. Following this update, we propose this publication as a practical guideline based on the published scientific guideline, but shortened and illustrated by flow charts. The main goal of this practical guideline is to increase understanding and allow the practitioner to implement the Nutrition in the ICU guidelines. All the items discussed in the previous guidelines are included as well as special conditions.
The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
: Eye-tracking methods have become a valuable tool for reading research, as they provide significant evidence on the behavioral and cognitive performance of developing readers. They also help identify reading behavior patterns among children with neurodevelopmental conditions, such as reading difficulties (RD) or attention-deficit hyperactivity disorder (ADHD). In this paper, we reviewed relevant literature (73 empirical studies) from 2008 to 2023 (15 years). We documented how reading performance was measured through eye-tracking methodology among typical and atypical readers across various languages. To ensure a rigorous and transparent review, we adhered to the PRISMA framework, defined keywords, established inclusion and exclusion criteria, conducted data extraction, and employed a multi-phase selection process. We focused on research samples, stimulus designs, independent variables, eye-tracking systems, and metrics. The results indicated that research involving typically developing children mainly included participants from primary school and employed various eye-tracking methods, with English being the most studied language. Studies on children with RD and ADHD varied significantly in participants' sample sizes, languages, and experimental designs. The discussion emphasizes the need for standardized data-collection procedures to enhance the reliability and comparability of findings, thereby supporting the development of effective interventions and instructional methods for reading difficulties.
α-Gal syndrome (AGS) is a type of allergy to red meat and other mammalian products that develops after a tick bite. Symptoms may include urticaria, angioedema, gastrointestinal and respiratory symptoms, and, most dangerously, anaphylactic shock. Among food allergies, it is considered unusual because: (i) the major allergen is not a protein, but a carbohydrate moiety Galα-1,3-Gal, which humans do not synthesize; (ii) it is caused by α-Gal-containing glycoconjugates injected during a tick bite; (iii) the hypersensitivity is effected by IgE antibodies which arise after a class switch from IgG and IgM-class antibodies; (iv) it seems to be triggered by α-Gal-containing glycolipids present in red meat, with delayed onset. Here, we evaluate glycans that may cause AGS, review the data about glycosyltransferases that synthesize α-Gal and related antigens and describe the immune mechanism behind AGS: sensitization and host response to ticks’ saliva. In addition, we consider future research avenues that may lead to a better understanding and management of AGS as a modern dietary affliction rooted in an old evolutionary trade-off.
