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Continuous Biosensing to Monitor Acute Systemic Inflammation, a Diagnostic Need for Therapeutic Guidance.
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315852.pdf (Publisher’s version ) (Open Access)Continuous monitoring of acute inflammation can become a very important next step for guiding therapeutic interventions in severely ill patients. This Perspective discusses the current medical need for patients with acute inflammatory diseases and the potential of continuous biosensing technologies. First, we discuss biomarkers that could help to monitor the state of a patient with acute systemic inflammation based on theoretical studies and empirical data. Then, based on the state of the art, we describe sensing strategies that could be applied for the continuous monitoring of acute inflammatory biomarkers, followed by challenges that must be overcome. Nanoswitch-based continuous biosensors enable suitable measurement frequencies but still lack sensitivity, while regeneration risks lower sensor reliability. Developments are still needed in bioreceptors and molecular architectures, regeneration techniques, combined with suitable sampling and sample pretreatment methods, for bringing continuous biosensing of inflammation closer to reality. Furthermore, collaborations between healthcare professionals and scientists, regulatory bodies, and biosensor engineers are needed for a successful translation of sensing technologies from the laboratory to clinical practice
The U.S. POINTER neurovascular ancillary study: Study design and methods.
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317733.pdf (Publisher’s version ) (Open Access)INTRODUCTION: POINTER Neurovascular (POINTER-NV) is an ancillary study that leverages the rich infrastructure and design of the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) to investigate neurovascular mechanisms that may underlie intervention effects on key brain outcomes. METHODS: A comprehensive neurovascular assessment is conducted at baseline, Month 12, and Month 24 using a variety of complementary non-invasive techniques including transcranial Doppler ultrasound, carotid ultrasound, echocardiography, tonometry, and continuous blood pressure and heart rate monitoring. Measurements are acquired at rest and during orthostatic challenges, hyperventilation, and carbon dioxide inhalation. RESULTS: The primary outcomes are baroreflex sensitivity and cerebral autoregulation. Secondary outcomes include aortic, carotid, and cerebral hemodynamics and various measures of autonomic function and vascular structure and function. DISCUSSION: POINTER-NV will provide critical insight into neurovascular mechanisms that may change with intensive lifestyle modification and promote improvements in cognition and overall brain health. HIGHLIGHTS: This study takes advantage of U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) to address key gaps in the field. POINTER Neurovascular (POINTER-NV) will provide insight into neurovascular mechanisms underlying dementia. POINTER-NV may help shed light on modifiable vascular contributions to dementia.01 februari 202
Tabaksblat en de botsende doelstellingen
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316020.pdf (Publisher’s version ) (Open Access
Digital Voice Assistants as Theatre: Apostrophic Interaction in Platform Discourses
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318389.pdf (Publisher’s version ) (Open Access)Radboud University, 14 april 2025Promotor : Smelik, A.M. Co-promotor : Niessen, N.279 p
Dissolved Mn(III) is a key redox intermediate in sediments of a seasonally euxinic coastal basin
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316725.pdf (Publisher’s version ) (Open Access
X-Linked autism type 9 caused by a hemizygote pathogenic variant in the TMLHE gene: Etiological diagnosis in an adult male with moderate intellectual disability
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315532.pdf (Publisher’s version ) (Open Access)INTRODUCTION: Levocarnitine is essential for brain functioning and fatty acid metabolism and stems largely from dietary sources. The Epsilon-Trimethyllysine Hydroxylase (TMLHE) gene encodes the enzyme N-Trimethyllysine hydroxylase (TMLH) which catalyses the first step in the biosynthesis of carnitine. Lack of TMLH enzyme activity is associated with developmental delay and autistic behaviours described as X-linked recessive autism, type 6 (OMIM#300872). PATIENT AND METHODS: Here, an institutionalized adult male patient with intellectual disability, autism, and challenging behaviours is presented in whom genetic analysis disclosed a novel pathogenic variant in the TMLHE gene. Extensive somatic, neurological, psychiatric, and neuropsychological investigations were performed next to examination of hematological and biochemical parameters including plasma carnitine status. Also, Whole Exome Sequencing (WES) and Next-Generation Metabolic Screening (NGMS) were performed. RESULTS: Moderate intellectual disability along with obsessive and aggressive behaviour in the context of autism spectrum disorders was established as well as symptoms from the catatonic spectrum. With WES, a novel variant in the TMHLE gene was identified and using NGMS, increased concentration of trimethyllysine and decreased concentration of γ-butyrobetaine were found resulting in a significantly decreased BB/TML ratio, confirming the pathogenicity of this variant. CONCLUSION: X-linked autism type 6 is characterized by moderate intellectual disability and symptoms from the autism spectrum in the absence of any dysmorphisms. To prevent regressive autistic episodes in young children, it is highly recommended to consider next-generation sequencing techniques as the first step in the differential diagnostic process of autism.6 p
Classification of Fibro-Osseous Tumors in the Craniofacial Bones Using DNA Methylation and Copy Number Alterations
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317566.pdf (Publisher’s version ) (Open Access)11 p
Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.
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315833.pdf (Publisher’s version ) (Open Access)Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model. In vitro, ERCC1-deficient brain ECs displayed increased senescence-associated secretory phenotype expression, reduced BBB integrity, and higher sprouting capacities due to an underlying dysregulation of the Dll4-Notch pathway. In line, EC-KO mice showed more P21(+) cells, augmented expression of angiogenic markers, and a concomitant increase in the number of brain ECs and pericytes. Moreover, EC-KO mice displayed BBB leakage and enhanced cell adhesion molecule expression accompanied by peripheral immune cell infiltration into the brain. These findings were confined to the white matter, suggesting a regional susceptibility. Collectively, our results underline the role of endothelial aging as a driver of impaired BBB function, endothelial sprouting, and increased immune cell migration into the brain, thereby contributing to impaired brain homeostasis as observed during the aging process
Characterization of nonlinear stress relaxation of the femoral and tibial trabecular bone for computational modeling.
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318179.pdf (Publisher’s version ) (Open Access)Computational models of orthopedic reconstructions are reliant on bone material properties, but viscoelastic behavior of trabecular bone is often ignored in numerical simulations. The inclusion of stress relaxation could be of importance for the accuracy of models simulating the primary stability of cementless implants. In this study, a material model to describe the nonlinear viscoelastic behavior of human trabecular bone was constructed based on uniaxial stress relaxation experiments. The relationship of bone mineral density (BMD) and stress relaxation was explored, and the material model was implemented in sample-specific finite element (FE) simulations. Cylindrical trabecular human bone specimens, from the distal femur and proximal tibia, were subjected to stress relaxation tests, undergoing compression with strains from 0.2 % to 0.8 % for 30 min on four consecutive days. The experimental data were extrapolated to 24 h. Similar levels of stress relaxation were found for femoral and tibial specimens, with an average 54.4 % stress relaxation and a maximum level of 81.6 %. Using a modified superposition model, the specimen-specific nonlinear stress relaxation behavior was captured. However, when the samples were considered collectively, no correlation was found between applied strain, BMD and the viscoelastic response. Therefore, the average level of stress relaxation in combination with existing BMD-stiffness relationships were implemented in FE simulations for each individual specimen. While the FE models, on average, overestimated the overall stiffness by 64 %, they were able to adequately capture the stress relaxation response.01 april 202