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From barrier breach to brain invasion: Modulators of T cell migration in Multiple Sclerosis
No full textMultiple Sclerosis (MS) is the most common neurological disorder in young adults, and every 5 minutes someone in the world is diagnosed with MS. The symptoms of MS present in unpredictable episodes impairing visual, sensory, physical, emotional and cognitive functions, which severely impact the lives of patients in the prime of their lives. The disease is caused by immune cells infiltrating into the brain and spinal cord attacking the insulating layer, called myelin, around the nerves. This causes disturbed signalling between neurons, leading to the array of symptoms. The immune system consists of many different cell types, of which the CD4+ T cell is believed to play a critical role in MS development, by opening and migrating through brain barriers. In healthy brains, T cells are not able to cross these barriers, but in people with MS these barriers are permeable, allowing T cells to enter and cause inflammation. In the first part of this thesis, I focussed on intercellular communication via small messengers called extracellular vesicles (EV). I investigated whether EV derived from blood brain barrier endothelial cells (BBB-EC) impacted BBB integrity, and if the size of these vesicles mattered. When the BBB was inflamed, much like in a brain of an MS patient, BBB-EC released more EV and their content mimicked the inflamed BBB. Large EV showed the most overlap with inflamed BBB cells. Thereby, EV were able to negatively regulate the integrity of the BBB. Next, EV were administered to mice induced with a MS-like disease, and we expected worsening of the disease. However, the group that received small EV actually got less sick and had less leakage of the BBB, indicating a protective effect. More research with EV derived from other origins is necessary. Nevertheless, this study indicates that BBBEV have a disease modifying effect in the context of MS. In the second part of this thesis, I investigated inflammasome activation within T cells, and determined whether it is crucial for BBB-transmigration, or if it is the result of migration. I first analysed inflammasome components in immune cells of MS patients and HD, and found no differences in directly isolated cells. However, I found that stimulation of CD46 induced inflammasome activation in both donor populations, and I established that in CD4+ T cells, the amount of inflammasome activation was higher in MS patients compared to HD. In the MS-like disease in mice, I found that inflammasome activation in CD4+ T cells increased in the central nervous system over time but not in peripheral lymphoid organs. I therefore looked further into the effect of inflammasome activation on the migratory capacities of T cells. Herein, I found indications that inflammasome activation is the result of BBBtransmigration rather than just contact with endothelial cells, and that this only happens in CD4+ T cells and not in other immune cells present in the blood. Finally, I looked into a specific molecule found on the endothelial cell layer that could be the trigger for inflammasome activation. In future research, I aim to validate this and show that blocking this interaction limits the pathogenicity of infiltrating T cells
Magnetic resonance spectroscopy and the menstrual cycle: a multi-centre assessment of menstrual cycle effects on GABA & GSH
No full textGamma-aminobutyric acid (GABA) and glutathione (GSH) play a significant role in the functioning of a healthy brain and can both be quantified using magnetic resonance spectroscopy (MRS). Several small-scale studies have suggested MRS measured GABA may fluctuate with the menstrual cycle, but the effects on GSH are unknown. Utilising recent developments in MRS acquisition, this multi-lab study explores this issue across 4 distinctive brain regions.This project applied tools developed under NIH grants R01 EB016089, R01 EB023963, and P41 EB031771. Tao Gong is supported by the National Natural Science Foundation of China [No. 82302149 (TG)], the Natural Science Foundation of Shandong Province [No. ZR2020QH267 (TG)], China Postdoctoral Science Foundation [No. 2022M711987 (TG)]. The centre for Brain Research is supported by a grant from the Priority Research Area (FutureSoc and qLife) under the Strategic Programme Excellence Initiative at Jagiellonian University
Supervised or Home-Based? Exploring the Best Exercise Approach for Knee Osteoarthritis Management: A Systematic Review and Meta-Analysis
No full textBackground/Objective: Knee osteoarthritis (OA) is a common and debilitating condition affecting older adults, often progressing to advanced stages and requiring total joint replacement. Exercise therapy is widely recognized as the first-line approach for the prevention and initial management of OA. This systematic review assessed the effectiveness of home-based exercises (HBEs) compared to supervised exercises in alleviating pain and reducing disability among patients with knee OA. Methods: A systematic search of PubMed, Cochrane Library, and ScienceDirect identified randomized controlled trials (RCTs) published between January 2001 and October 2024. Methodological quality was evaluated using the Physiotherapy Evidence Database (PEDro) scale, and a meta-analysis was conducted to quantify the efficacy of these interventions. Results: Ten RCTs involving 917 patients were included, ranging in moderate to high methodological quality (PEDro score: 6.3 +/- 1.2). Intervention durations ranged from 4 to 12 weeks. Both supervised and HBEs were found to be effective, but supervised exercises demonstrated statistically significant improvements in pain (SMD = -0.45 [95% CI -0.79; -0.11], p = 0.015) and disability (SMD = -0.28 [95% CI -0.42; -0.14], p < 0.001) compared to HBEs. Conclusions: Despite the superiority of supervised exercises over HBEs, considering the cost-effectiveness and ease of implementation of HBEs, we developed recommendations to create a hybrid rehabilitation program that combines both approaches to maximize clinical outcomes.VLIR-UOS through their SI program; [R-13396
Systematic Molecular Influenza A/B Screening Upon Hospital Admission in Belgium, January-April 2022: Positivity Ratios and Viral Loads According to Symptomatology, Age, and Vaccination Status
No full textThree hospitals implemented molecular point-of-care tests (POCTs) to screen patients for SARS-CoV-2 infection upon admission during the 2021/2022 influenza season, which in Belgium lasted from January to April 2022. The samples were simultaneously tested for influenza A/B. Influenza positivity at admission was examined in relation to patient characteristics and symptomatology. Influenza POCTs were performed on all patients requiring urgent hospitalization, regardless of the admission reason. A total of 9327 patients were included in the study, of which 411 (4.4%) tested positive for influenza A/B. Asymptomatic infection and mild illness accounted for respectively 11.2% (95% CI: 8.5%-14.6%), and 43.3% (95% CI: 38.6%-48.1%) of the cases. A total of 66% (95% CI: 60%-72%) of all patients in these symptom categories (asymptomatic and mild illness) showed a high viral load (cycle threshold [Ct] < 24). Only in 30 (7.3%, 95% CI: 5.2%-10.2%) of all cases and in two (4.4%, 95% CI: 1.2%-14.5%) of the asymptomatic cases, the symptomatology worsened during hospital stay. Coinfections with both influenza and SARS-CoV-2 occurred in 35 patients (8.5% of all influenza positive patients). There was no difference in symptomatology between patients with co-infections and those with an influenza mono-infection. Patients could not be reliably categorized into carriers with low versus high viral loads based on symptomatology, age, and vaccination status. More than half of the influenza-positive individuals were either asymptomatic or had mild symptoms upon admission, while often carrying high viral loads. Our results show that without screening of patients at hospital admission, a considerable number of patients with a high viral load may be incorrectly classified as being not infectious
A configurational approach to strategic change in family firms
No full textStrategic change is essential for an organization's long-term performance and survival. Research has investigated how governance structures, organizational values, capabilities, and firm size, in isolation from one another, influence family firms' strategic change, yet insights in family firm literature suggest the need to examine the fit among these dimensions. We employ a configurational approach and a framework built from models of fit in family firm literature to examine the interdependence among these dimensions. Using a primary dataset of 275 Belgian private family firms and fuzzy-set qualitative comparative analysis (fsQCA), we identify six configurations leading to high levels of strategic change and three configurations explaining low levels of strategic change. This study contributes to the literature by advancing our understanding of how multiple interdependent dimensions, namely, governance structures, organizational values, capabilities, and firm size, combine to better explain strategic change levels in family firms. The findings also provide concrete formulas for practitioners to create a fit among specific factors in these dimensions to promote strategic change.The authors are grateful for the financial support from Strategic Basic Research (SBO) (Grant S002919N) of the Research Foundation Flanders (FWO), which allowed us to conduct the study
The EU Legal Framework on Transboundary Air Quality and Pollution: Exploring the Mismatch between Transnationality in Legislation and Its Use in Practice
No full textThe point of departure of this contribution is the observation that air pollution does not stop at borders. Therefore, both at the international and EU level, frameworks of cooperation among Member States have been set up by the legislators. Such cooperation is an example of a transnational element existing in environmental law. This article more specifically analyses the transnational elements present in two EU Directives regulating air quality: Directive 2008/50/EC on ambient air quality, and Directive 2016/2284/EU on national emission ceilings. This analysis shows the possible transnational avenues at Member States' disposal to further enhance air quality. This article furthermore delves into the question of whether Member States use these tools in practice, by looking at cooperation among regions in Belgium and France as a case study. Accordingly, this article identifies a mismatch between the transnational cooperation opportunities identified in the legislation, and the very little use of such opportunities in practice
Attaining 15.1% Efficiency in Cu2ZnSnS4 Solar Cells Under Indoor Conditions Through Sodium and Lithium Codoping
No full textThe rising demand for sustainable low-power devices has driven interest in indoor photovoltaic (IPV) technologies for Internet of Things (IoT) applications. Composed of earth-abundant and non-toxic elements, Kesterite-based Cu2ZnSnS4 (CZTS) solar cells are highly attractive for IPV. This study systematically investigates the effects of sodium (Na), lithium (Li), and Na-Li co-doping on solution-processed CZTS devices. A comprehensive analysis reveals that Na-doping substantially improves crystallinity and grain morphology, significantly boosting efficiency, whereas Li alone has minimal impact. Notably, Na-Li co-doping achieves a 10.1% efficiency under AM 1.5G illumination, outperforming both the reference and singly doped devices. The co-doping synergy arises from Na-induced grain growth and Li-induced defect passivation and carrier concentration regulation. These devices exhibit high adaptability under 20 different indoor lighting conditions representative of real-world environments, achieving up to 15.1% power conversion efficiency under 3000 K illumination at 2.93 mW cm-2;-the highest reported indoor efficiency for CZTS cells. Their stable open-circuit voltage, high fill factor, and consistent efficiency across various color temperatures and intensities underline their suitability for IPV applications. Future work should focus on improving bandgap alignment with indoor light spectra to further enhance the efficiency of this eco-friendly technology for IoT energy solutions.This project received funding from the European Union’s H2020 research and innovation program under grant agreement number 866018 (SENSATE) and by the Science Ministry of Spain projects number PID2023-148976OB-C41 (CURIO-CITY). The authors from UPC belong to the Micro and Nanotechnologies for Solar Energy Group (MNTSolar) Consolidated Research Group of the “Generalitat de Catalunya” (2021 SGR 01286). Y.G. thanks the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 10115148. R.S. thanks FWO for the funding through the Fundamental Research Ph.D. Fellowship (1178024N) and Travel Grant for a long stay abroad (V462623N). D.P. and A.P. thank projects SCALING (PID2022-138434OB-C52) and InnoPV (PID2022-140226OB-C31) funded by MCIN/AEI/10.13039/501100011033/ FEDER, UE. S.G. thanks the Serra Húnter program. M.P. thanks InnoPV (PID2022-140226OB-C32) funded by MCIN/AEI/10.13039/501100011033/ FEDER, UE. Z.J. thanks financial support from Spanish Ministry of Science, Innovation through the Ramon y Cajal fellowship (RYC2021-033239-I). E.S. is grateful to ICREA Academia program
No Boundaries and Naturally‐Defined Boundaries Obtained via the Electrostatic Potential
No full textThis paper discusses the use of the electrostatic potential in both recent and older literature, with an emphasis upon a 2022 Molecular Physics article by Politzer and Murray entitled ”Atoms do exist in molecules: analysis using electrostatic potentials at nuclei”. We discuss electrostatic potentials at nuclei and how they easily lead to atoms in molecules, without physically separating the individual atoms. We further summarize the work by the Politzer group on definitions of atomic radii by means of the electrostatic potential. The earlier studies began in the 1970’s and continued through the 1990’s. Unfortunately, access to these older publications is often limited, cfr. digital libraries often limit the authorized access until a certain publication year, and these papers are often not cited in current publications. Although still being highly interesting and relevant, this older literature is in danger of being lost. Digging into this older literature thus opens up new views. Our feeling is that Peter passed ‘on’ a vision that boundaries do not exist between atoms in molecules, but that some useful and meaningful radii can be obtained using the electrostatic potential between atoms in molecules
Charge-Transfer States at the Fullerene Interface Cause Nonradiative Recombination Losses in Sn-Based Perovskite Solar Cells
No full textTin-based perovskite solar cells (PSCs) are emerging as a more environmentally friendly alternative to traditional PSCs that typically contain toxic lead. In this work, we study the influence of the Sn-perovskite/fullerene interface on the open-circuit voltage (V oc). When the fullerene derivative ICBA is used as the electron transport layer, the V oc reaches 0.68 V, while the band gap of the Sn-perovskite is 1.44 eV, giving a voltage deficit of 0.76 V. Using PCBM as the electron transport layer, this deficit is 0.19 V higher. Herein, we identify through Fourier transform photocurrent spectroscopy and luminescence measurements that interfacial charge-transfer states at the Sn-perovskite/fullerene interface induce a nonradiative recombination channel. The energy of these states should be increased in order to mitigate voltage losses at the contacts.The authors acknowledge funding through the projectPERCISTAND (Grant Agreement 850937). S.H. and M.V.L.acknowledge financial support by the Flanders ResearchFoundation (FWO) strategic basic research doctoral grant 1S31922N and through a postdoctoral fellowship (1270123N),respectively