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APOE deficiency inhibits amyloid-facilitated (A) tau pathology (T) and neurodegeneration (N), halting progressive ATN pathology in a preclinical model
No full textIn AD, amyloid pathology (A) precedes progressive development of tau pathology (T) and neurodegeneration (N), with the latter (T/N) processes associated with symptom progression. Recent anti-amyloid beta (A beta) clinical trials raise hope but indicate the need for multi-targeted therapies, to effectively halt clinical AD and ATN pathology progression. APOE-related putative protective mutations (including APOE3Christchurch, RELN-COLBOS) were recently identified in case reports with exceptionally high resilience to autosomal dominant AD. In these cases, Nature provided proof of concept for halting autosomal dominant AD and ATN progression in humans, despite a high amyloid load, and pointing to the APOE pathway as a potential target. This is further supported by the recent identification of APOE4 homozygosity as genetic AD. Here we studied the role of APOE in a preclinical model that robustly mimics amyloid-facilitated (A) tau pathology (T) and subsequent neurodegeneration (N), denoted as ATN model, generated by crossing 5xFAD (F+) and TauP301S (T+) mice. We show that APOE deficiency, markedly inhibited progression to tau pathology and tau-induced neurodegeneration in this ATN model, despite a high A beta load, reminiscent of the high resilience ADAD case reports. Further study identified, despite increased A beta load (W02 stained), a significant decrease in compacted, dense core plaques stained by ThioS in APOE deficient ATN mice. Furthermore, single-cell RNA sequencing (scRNA-seq) showed a crucial role of APOE in microglial conversion beyond homeostatic microglia to reactive and disease associated microglia (DAM) in this ATN preclinical model. Microglial elimination significantly decreased amyloid-driven tau pathology, in the presence of APOE, but not in APOE deficient mice. Together the data demonstrate that APOE deficiency inhibits amyloid-driven tau pathology and subsequent neurodegeneration, by pleiotropic effects including prevention of dense core plaque formation and halting conversion of homeostatic microglia. We here present a model recapitulating inhibition of amyloid-facilitated tau pathology by APOE deficiency despite high A beta load, important for understanding the role of APOE, and APOE-dependent processes in ATN progression and its therapeutic exploitation in AD.TV received funding from the Research Council of KU Leuven, the Queen Elisabeth Medical Foundation for Neurosciences and the VIB. IDW received funding from Stichting Alzheimer Onderzoek Belgium (Standard Grants – Grant Cycles started 2021–2024, SAO2020022, SAO20240028) and from Methusalem Fund UHasselt. Scholarships of FWO supported ICS (postdoc) and JH (PhD) (G0C6819N, 1190025N). SK is a PhD assistant supported by Hasselt University. BB received funding from the Special Research Foundation of UHasselt (BOF17DOCLI01). MK was supported by a SALK-grant from the government of Flanders, by an Odysseus-grant (G0G1216FWO) and senior research project (G080121N) of the FWO and by a BOF grant (21GP17BOF) from Hasselt Universit
Promoting sustainable development via stakeholder engagement in higher education
No full textBackgroundHigher education institutions (HEI) are uniquely positioned to contribute to sustainable development through education, research, community engagement, and policy influence. In this context, stakeholder engagement is recognised as an important strategy, since involving diverse groups in decision-making processes, HEIs can harness a wealth of perspectives, expertise, and resources, fostering more inclusive, innovative, and effective approaches to sustainability. There is a perceived need for studies that explore the contribution of various stakeholders in higher education, and suggest ways to optimise their participation in processes. Against this background, this paper seeks to bridge the gap between theoretical frameworks of stakeholder engagement and practical applications within the context of sustainable development in higher education.ResultsBy examining 29 real-world case studies and best practices, this paper provides actionable insights and guidance for HEIs to enhance their sustainability efforts. Findings from the analysis of cases in Europe, Africa, Asia, and North and South America were consolidated into ten guidelines for HEIs seeking to promote sustainable development through stakeholder engagement. The analysis of trends identified three clusters: (i) HEI's role in sustainable development through stakeholder engagement and Sustainable Development Goals (SDGs); (ii) human-centred sustainability via transformative learning and community empowerment; and (iii) education and interdisciplinary approaches to sustainability.ConclusionsThe nature of the work performed, and the scope of the activities of HEIs put them in a key position to drive sustainable development by engaging diverse stakeholders across academic and societal contexts, including students, faculty, administration, industry partners, and the broader community. Inclusive participation and interdisciplinary educational programmes that integrate sustainability across curricula are key to effective stakeholder engagement. In addition, institutional commitment, including strong leadership and strategic policies, is essential for advancing sustainability initiatives, while partnerships with local communities and industries amplify the practical impact of sustainability efforts while addressing real-world challenges.The authors are grateful for the support of the National Council for Scientifc and Technological Development (CNPq/Brazil) under the Grant Number 304145/2021 - 1
Trough concentrations of cabotegravir and rilpivirine and their association with detectable viral load in people with HIV on long-acting treatment
No full textBackground Cabotegravir (CAB) and rilpivirine (RPV) constitute the first complete non-oral ART regimen for HIV-1 treatment. Due to virologic failure (VF) with resistance in clinical trials, concerns persist regarding broader use in clinical practice. In particular, the role of trough drug concentrations in relation to viremia and VF remains unclear. This study explored the association between CAB and RPV trough concentrations in a retrospective, single-center study. Methods We retrospectively analyzed data from the HIV research and clinical care center MVZ M & uuml;nchen am Goetheplatz, Germany. Inclusion criteria were CAB and RPV long-acting therapy every 8 weeks without additional ART and availability of drug concentrations within 7 days before the next administration. A modified Wilcoxon test assessed differences in concentrations between samples with HIV-1 RNA = 20 copies/mL. Odds ratios (ORs) were estimated using generalized estimation equation (GEE) models, and ROC analysis identified potential alternative drug concentration thresholds. Findings A total of 737 samples from 185 individuals were included. Median CAB concentrations were 1,480 g/L (IQR: 1,097-1,955) vs. 1,180 mu g/L (879-1,570) for samples with HIV-1 RNA levels = 20 copies/mL, respectively (p = 0.001); for RPV, 77 g/L (53-107) vs. 63 mu g/L (47-87) (p = 0.001). Using ROC-derived thresholds, low concentrations of CAB (g/L) or RPV (g/L) were found in 11.5% and 25.4% of samples, respectively, and associated with ORs of 2.4 (1.5-4.0) and 2.3 (1.4-3.8) for HIV-1 RNA >= 20 copies/mL. Interpretation Lower CAB and RPV concentrations were associated with viremia, particularly using the ROC-derived thresholds. Among individuals with VF and available drug concentration data, 87.5% had at least one drug below these thresholds. Further research on therapeutic drug monitoring is warranted.Open Access funding enabled and organized by Projekt DEAL
AdaptRehab VR: Development of an Immersive Virtual Reality System for Upper Limb Stroke Rehabilitation Designed for Low- and Middle-Income Countries Using a Participatory Co-Creation Approach
No full textStroke remains a significant global health challenge, particularly in low- and middle-income Countries (LMICs), where two-thirds of stroke-related deaths occur, and disability-adjusted life years are seven times higher compared to high-income Countries (HICs). The majority of stroke survivors suffer from upper limb impairment, severely limiting their daily activities and significantly diminishing their overall quality of life. Rehabilitation plays a critical role in restoring function and independence, but it faces challenges such as low engagement, limited customization, difficulty tracking progress, and accessibility barriers, particularly in LMICs. Immersive virtual reality (imVR) has shown promise in addressing these challenges, but most commercial imVR systems lack therapeutic design and cultural adaptation. This study aimed to develop culturally adaptable imVR games for upper limb stroke rehabilitation (ULSR) in the context of LMICs, with a particular focus on Ethiopia. The AdaptRehab VR system was developed including six imVR games (Basket Bloom, Strike Zone, TapQuest, FruitFall Frenzy, Precision Pitch, and Bean Picker Pro) through co-creation approaches involving Ethiopian and Belgian physiotherapists, stakeholders, and patients, incorporating game development mechanics in rehabilitation, such as therapeutic aims, cultural factors, feedback, automatic progression recording, task variety, and personalized rehabilitation. It was designed with the Unity 3D engine and Oculus Quest headsets, supporting controllers and hand tracking. This culturally tailored imVR platform has demonstrated significant potential to enhance ULSR accessibility, patient motivation, and outcomes in resource-constrained settings, addressing critical gaps in stroke rehabilitation solutions. In conclusion, the AdaptRehab VR system was successfully developed as a culturally contextualized imVR platform tailored to tackle ULSR challenges in LMICs, with a specific focus on Ethiopia.This research was funded by the NASCERE project, a joint PhD program between Jimma University and Hasselt University funded by the VLIR-UOS
Sex differences in the association between long-term ambient particulate air pollution and the intestinal microbiome composition of children
No full textThe intestinal microbiome is essential for gastrointestinal and overall health, yet its response to air pollution in children remains underexplored. In a study involving 412 young children from the ENVIRONAGE cohort, stool samples were analysed via Illumina Miseq sequencing to assess microbiome alpha diversity (observed richness, species evenness, and Shannon diversity) and composition. Exposure to previous year particulate air pollution (black carbon, PM2.5, coarse PM, and PM10) was modeled using high-resolution spatial-temporal interpolation models. Multiple linear regression models were adjusted for a priori selected covariables and stratified by sex. Furthermore, we performed a differential relative abundance analysis at family and genus level, while accounting for the same covariables. Statistically significant effect modification by sex was apparent for several intestinal alpha diversity indices and air pollutants. In boys, we observed negative associations between particulate air pollution exposure and intestinal microbiome richness (estimates ranging from -5.55 to -9.06 per interquartile range (IQR) increase in particulate air pollution exposure) and Shannon diversity (estimates ranging from -0.058 to -0.095 per IQR increase). Differently, in girls non-significant positive associations were observed with species evenness (estimates ranging from 0.019 to 0.020 per IQR increase) and Shannon diversity (estimate 0.065 per IQR increase in black carbon). After multiple testing correction, we reported several bacterial families and genera (Streptococcaceae, Clostridiales Incertae Sedis XIII, Coriobacteriaceae, Streptococcus, and Paraprevotella) to be oppositely associated with particulate air pollution exposure in boys and girls. Our findings show a sex-dependent association between particulate air pollution exposure and intestinal microbiome composition, highlighting boys as potentially more vulnerable to diversity loss associated with childhood exposure to particulate pollution.The ENVIRONAGE birth cohort was initiated by ERC grant (ERC2012-StG.310898) and the current work is supported by grants from the Interuniversity Special Research Fund (iBOF) (grant number 01IB1320, FLEXiGUT). Tim S. Nawrot is a Methusalem grant holder. Thessa Van Pee holds a doctoral fellowship from the Research Foundation Flanders (FWO), grant number: 11C7421N. We thank all mother-child pairs for participating in the stud
Spring into innovation: connecting minds, transforming care, saving lives
No full textWith the arrival of spring, the long-anticipated congress season is in full bloom, kicking off with the Acute Cardiovascular Care Congress in Florence, Italy. This vibrant gathering unites the global acute cardiovascular care community for an inspiring exchange of knowledge, groundbreaking research, and professional collaboration. But the momentum doesn't stop there-April also brings the prestigious American College of Cardiology (ACC) Meeting in Chicago, where the European Heart Journal-Acute Cardiovascular Care takes center stage in capturing the latest scientific advancements. These landmark events offer an unparalleled platform for cutting-edge science, fostering collaborations, and exploring innovations shaping the future of cardiovascular medicine
12-Month DAPT(PIONEER III) Vs. 1-Month D apt (PIONEER IV): Comparative Observational Assessment of Bleeding and Ischemic Events After Aspirin Cessation in Patients Treated With Healing-Targeted Supreme Sirolimus-Eluting Stent (HT Supreme)
No full textPsychometric properties of the modified reaching performance scale in persons with multiple sclerosis
No full textA valid and reliable assessment tool to describe the quality of the movement pattern of reaching can provide valuable insights into motor performance deficits in persons with MS (pwMS). The Reaching Performance Scale, developed for stroke, is a promising scale to assess movement patterns in pwMS. However, psychometric properties of the scale are lacking in pwMS
The Impact of Exercise Training on the Brain and Cognition in Type 2 Diabetes, and its Physiological Mediators: A Systematic Review
No full textBackgroundType 2 diabetes (T2DM) affects brain structure and function, and is associated with an increased risk of dementia and mild cognitive impairment. It is known that exercise training has a beneficial effect on cognition and brain structure and function, at least in healthy people, but the impact of exercise training on these aspects remains to be fully elucidated in patients with T2DM.ObjectiveTo determine the impact of exercise training on cognition and brain structure and function in T2DM, and identify the involved physiological mediators.MethodsThis paper systematically reviews studies that evaluate the effect of exercise training on cognition in T2DM, and aims to indicate the most beneficial exercise modality for improving or preserving cognition in this patient group. In addition, the possible physiological mediators and targets involved in these improvements are narratively described in the second part of this review. Papers published up until the 14th of January 2025 were searched by means of the electronic databases PubMed, Embase, and Web of Science. Studies directly investigating the effect of any kind of exercise training on the brain or cognition in patients with T2DM, or animal models thereof, were included, with the exception of human studies assessing cognition only at one time point, and studies combining exercise training with other interventions (e.g. dietary changes, cognitive training, etc.). Study quality was assessed by means of the TESTEX tool for human studies, and the CAMARADES tool for animal studies.ResultsFor the systematic part of the review, 22 papers were found to be eligible. 18 out of 22 papers (81.8%) showed a significant positive effect of exercise training on cognition in T2DM, of which two studies only showed significant improvements in the minority of the cognitive tests. Four papers (18.2%) could not find a significant effect of exercise on cognition in T2DM. Resistance and endurance exercise were found to be equally effective for achieving cognitive improvement. Machine-based power training is seemingly more effective than resistance training with body weight and elastic bands to reach cognitive improvement. In addition, BDNF, lactate, leptin, adiponectin, GSK3 beta, GLP-1, the AMPK/SIRT1 pathway, and the PI3K/Akt pathway were identified as plausible mediators directly from studies investigating the effect of exercise training on brain structure and function in T2DM. Via these mediators, exercise training induces multiple beneficial brain changes, such as increased neuroplasticity, increased insulin sensitivity, and decreased inflammation.ConclusionOverall, exercise training beneficially affects cognition and brain structure and function in T2DM, with resistance and endurance exercise having similar effects. However, there is a need for additional studies, and more methodological consistency between different studies in order to define an exercise program optimal for improving cognition in T2DM. Furthermore, we were able to define several mediators involved in the effect of exercise training on cognition in T2DM, but further research is necessary to unravel the entire process.Internal funding of Hasselt University (23OWB01BOF) was received to assist with the preparation of this manuscript