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Magnetic resonance imaging (MRI) is a critical diagnostic tool and monitoring modality for multiple sclerosis (MS), frequently employing gadolinium-based contrast agents (Gd). However, concerns regarding the accumulation of Gd have prompted international guidelines (MAGNIMS-CMSC-NAIMS, 2021) to advocate for the limitation of Gd utilization. Consequently, we assessed of the impact of the 2021 guidelines on the use of Gd in MRI in MS patients in Germany by conducting a retrospective analysis of MRI data from 12,833 MS patients in the German MS Register (2019–2024). Generalized additive models were employed to analyze Gd use trends over time by MRI type (cranial, spinal, combined). From 2020 to 2024, a significant decline in Gd use was observed, with percentages dropping from 74.2 to 41.2% in cranial MRI, from 78.2 to 39.2% in spinal MRI and from 81.8 to 59.0% in combined MRI ( p  < 0.001). The most substantial decline occurred within the initial five years of MS. Gd use in MS MRI scans has significantly decreased in line with the updated guidelines. Nevertheless, its persistent utilization in over one-third of cases necessitates further examination.

Cytokine proteins are known as biomarker molecules, characteristic of a disease or specific body condition. Monitoring of the cytokine pattern in body fluids can contribute to the diagnosis of diseases. Here we report on the development of an array comprised of different anti-cytokine antibodies on an activated solid support coupled with a fluorescence readout mechanism. Optimization of the array preparation was done in regard of spot homogeneity and spot size. The proinflammatory cytokines Tumor Necrosis Factor alpha (TNFα) and Interleukin 6 (IL-6) were chosen as the first targets of interest. First, the solid support for covalent antibody immobilization and an adequate fluorescent label were selected. Three differently functionalized glass substrates for spotting were compared: amine and epoxy, both having a two-dimensional structure, and the NHS functionalized hydrogel (NHS-3D). The NHS-hydrogel functionalization of the substrate was best suited to antibody immobilization. Then, the optimization of plotting parameters and geometry as well as buffer media were investigated, considering the ambient analyte theory of Roger Ekins. As a first step towards real sample studies, a proof of principle of cytokine detection has been established.

RNA aptamers for tumor necrosis factor-alpha (TNFα), for which functionality was demonstrated in L929 cells, show only little affinity for the protein in vitro. Detailed investigation of the aptamer-protein interaction by surface plasmon resonance and quartz crystal microbalance analysis revealed that affinity is not the only crucial parameter for efficacy and functionality of those aptamers. Instead, the sensitive equilibrium of the monomeric and homotrimeric form of soluble TNFα decides on aptamer binding. Our results show that the field of application and the source of TNFα have to be carefully defined before selection of aptamer sequences.

RNA aptamers for tumor necrosis factor-alpha (TNF[alpha]), for which functionality was demonstrated in L929 cells, show only little affinity for the protein in vitro. Detailed investigation of the aptamer-protein interaction by surface plasmon resonance and quartz crystal microbalance analysis revealed that affinity is not the only crucial parameter for efficacy and functionality of those aptamers. Instead, the sensitive equilibrium of the monomeric and homotrimeric form of soluble TNF[alpha] decides on aptamer binding. Our results show that the field of application and the source of TNF[alpha] have to be carefully defined before selection of aptamer sequences.

Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional’s approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2–ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

The goal of achieving the large-scale production of zero-emission vehicles by 2035 will create high expectations for electric vehicle (EV) development and availability. Currently, a major problem is the lack of suitable batteries and battery materials in large quantities. The rechargeable zinc–air battery (RZAB) is a promising energy-storage technology for EVs due to the environmental friendliness and low production cost. Herein, iron, cobalt, and nickel phthalocyanine tri-doped electrospun carbon nanofibre-based (FeCoNi-CNF) catalyst material is presented as an affordable and promising alternative to Pt-group metal (PGM)-based catalyst. The FeCoNi-CNF-coated glassy carbon electrode showed an oxygen reduction reaction/oxygen evolution reaction reversibility of 0.89 V in 0.1 M KOH solution. In RZAB, the maximum discharge power density (Pmax) of 120 mW cm−2 was obtained with FeCoNi-CNF, which is 86% of the Pmax measured with the PGM-based catalyst. Furthermore, during the RZAB charge–discharge cycling, the FeCoNi-CNF air electrode was found to be superior to the commercial PGM electrocatalyst in terms of operational durability and at least two times higher total life-time.

Treatment of peripheral nerve lesions remains a major challenge due to poor functional recovery; hence, ongoing research efforts strive to enhance peripheral nerve repair. In this study, we aimed to establish three-dimensional tissue-engineered bands of Büngner constructs by subjecting Schwann cells (SCs) embedded in fibrin hydrogels to mechanical stimulation. We show for the first time that the application of strain induces (i) longitudinal alignment of SCs resembling bands of Büngner, and (ii) the expression of a pronounced repair SC phenotype as evidenced by upregulation of BDNF, NGF, and p75NTR. Furthermore, we show that mechanically aligned SCs provide physical guidance for migrating axons over several millimeters in vitro in a co-culture model with rat dorsal root ganglion explants. Consequently, these constructs hold great therapeutic potential for transplantation into patients and might also provide a physiologically relevant in vitro peripheral nerve model for drug screening or investigation of pathologic or regenerative processes.

Members of the NETWORKED (NET) family are involved in actin-membrane interactions. Here we show that two members of the NET family, NET4A and NET4B, are essential for normal guard cell actin reorganization, which is a process critical for stomatal closure in plant immunity. NET4 proteins interact with F-actin and with members of the Rab7 GTPase RABG3 family through two distinct domains, allowing for simultaneous localization to actin filaments and the tonoplast. NET4 proteins interact with GTP-bound, active RABG3 members, suggesting their function being downstream effectors. We also show that RABG3b is critical for stomatal closure induced by microbial patterns. Taken together, we conclude that the actin cytoskeletal remodelling during stomatal closure involves a molecular link between actin filaments and the tonoplast, which is mediated by the NET4-RABG3b interaction. We propose that stomatal closure to microbial patterns involves the coordinated action of immune-triggered osmotic changes and actin cytoskeletal remodelling likely driving compact vacuolar morphologies. Protein tethers can bridge the actin cytoskeleton with cellular membranes. Here, the authors show that two members of the NETWORKED family, NET4A and NET4B, tether actin filaments and the tonoplast through interaction with RABG3b and are essential for actin reorganization during stomatal closure in plant immunity.

Background Despite growing evidence that deprescribing can improve clinical outcomes, quality of life and reduce the likelihood of adverse drug events, the practice is not widespread, particularly in hospital settings. Clinical risk assessment tools, like the Drug Burden Index (DBI), can help prioritise patients for medication review and prioritise medications to deprescribe, but are not integrated within routine care. The aim of this study was to conduct formative usability testing of a computerised decision support (CDS) tool, based on DBI, to identify modifications required to the tool prior to trialling in practice. Methods Our CDS tool comprised a DBI MPage in the electronic medical record (clinical workspace) that facilitated review of a patient’s DBI and medication list, access to deprescribing resources, and the ability to deprescribe. Two rounds of scenario-based formative usability testing with think-aloud protocol were used. Seventeen end-users participated in the testing, including junior and senior doctors, and pharmacists. Results Participants expressed positive views about the DBI CDS tool but testing revealed a number of clear areas for improvement. These primarily related to terminology used (i.e. what is a DBI and how is it calculated?), and consistency of functionality and display. A key finding was that users wanted the CDS tool to look and function in a similar way to other decision support tools in the electronic medical record. Modifications were made to the CDS tool in response to user feedback. Conclusion Usability testing proved extremely useful for identifying components of our CDS tool that were confusing, difficult to locate or to understand. We recommend usability testing be adopted prior to implementation of any digital health intervention. We hope our revised CDS tool equips clinicians with the knowledge and confidence to consider discontinuation of inappropriate medications in routine care of hospitalised patients. In the next phase of our project, we plan to pilot test the tool in practice to evaluate its uptake and effectiveness in supporting deprescribing in routine hospital care.