554 research outputs found
Advanced glycation end products and age-related diseases in the general population
In this thesis, epidemiological, nutritional, and gut microbiome related studies are presented to illustrate the relation of advanced glycation end products (AGEs) with age-related diseases. The studies are embedded in the Rotterdam Study, a cohort of the Dutch general population of middle-aged and elderly adults. The amount of skin AGEs measured as SAF was used as a representative of the long-term AGE burden. Chapter 1 gives an overview of the whole thesis (Section 1.1) and gives a brief introduction to AGEs and their implications in disease pathophysiology. Chapter 2 focuses on the interplay of AGEs in the skin and clinical and lifestyle factors, and Chapter 3 concerns the link of skin and dietary AGEs with age-related diseases. Chapter 4 discusses the interpretations and implications of the findings, major methodological considerations, and pressing questions for future research
Advanced glycation end products and age-related diseases in the general population
In this thesis, epidemiological, nutritional, and gut microbiome related studies are presented to illustrate the relation of advanced glycation end products (AGEs) with age-related diseases. The studies are embedded in the Rotterdam Study, a cohort of the Dutch general population of middle-aged and elderly adults. The amount of skin AGEs measured as SAF was used as a representative of the long-term AGE burden. Chapter 1 gives an overview of the whole thesis (Section 1.1) and gives a brief introduction to AGEs and their implications in disease pathophysiology. Chapter 2 focuses on the interplay of AGEs in the skin and clinical and lifestyle factors, and Chapter 3 concerns the link of skin and dietary AGEs with age-related diseases. Chapter 4 discusses the interpretations and implications of the findings, major methodological considerations, and pressing questions for future research
The medical applications of hyperpolarized Xe and nonproton magnetic resonance imaging
Hyperpolarized 129Xe (HP 129Xe) magnetic resonance imaging (MRI) is a relatively young
field which is experiencing significant advancements each year. Conventional proton MRI is
widely used in clinical practice as an anatomical medical imaging due to its superb soft tissue
contrast. HP 129Xe MRI, on the other hand, may provide valuable information about internal organs
functions and structure. HP 129Xe MRI has been recently clinically approved for lung imaging in
the United Kingdom and the United States. It allows quantitative assessment of the lung function
in addition to structural imaging. HP 129Xe has unique properties of anaesthetic, and may transfer
to the blood stream and be further carried to the highly perfused organs. This gives the opportunity
to assess brain perfusion with HP 129Xe and perform molecular imaging. However, the further
progression of the HP 129Xe utilization for brain perfusion quantification and molecular imaging
implementation is limited by the absence of certain crucial milestones.
This thesis focused on providing important stepping stones for the further development of
HP 129Xe molecular imaging and brain imaging. The effect of glycation on the spectroscopic
characteristics of HP 129Xe was studied in whole sheep blood with magnetic resonance
spectroscopy. An additional peak of HP 129Xe bound to glycated hemoglobin was observed. This
finding should be implemented in the spectroscopic HP 129Xe studies in patients with diabetes. [...
Cerebrovascular dysfunction in cerebral small vessel disease
INTRODUCTION:
Cerebral small vessel disease (SVD) is the cause of a quarter of all ischaemic strokes and is postulated to have a role in up to half of all dementias. SVD pathophysiology remains unclear but cerebrovascular dysfunction may be important. If confirmed many licensed medications have mechanisms of action targeting vascular function, potentially enabling new treatments via drug repurposing. Knowledge is limited however, as most studies assessing cerebrovascular dysfunction are small, single centre, single imaging modality studies due to the complexities in measuring cerebrovascular dysfunctions in humans. This thesis describes the development and application of imaging techniques measuring several cerebrovascular dysfunctions to investigate SVD pathophysiology and trial medications that may improve small blood vessel function in SVD.
METHODS:
Participants with minor ischaemic strokes were recruited to a series of studies utilising advanced MRI techniques to measure cerebrovascular dysfunction. Specifically MRI scans measured the ability of different tissues in the brain to change blood flow in response to breathing carbon dioxide (cerebrovascular reactivity; CVR) and the flow and pulsatility through the cerebral arteries, venous sinuses and CSF spaces. A single centre observational study optimised and established feasibility of the techniques and tested associations of cerebrovascular dysfunctions with clinical and imaging phenotypes. Then a randomised pilot clinical trial tested two medicationsâ (cilostazol and isosorbide mononitrate) ability to improve CVR and pulsatility over a period of eight weeks. The techniques were then expanded to include imaging of blood brain barrier permeability and utilised in multi-centre studies investigating cerebrovascular dysfunction in both sporadic and monogenetic SVDs.
RESULTS:
Imaging protocols were feasible, consistently being completed with usable data in over 85% of participants. After correcting for the effects of age, sex and systolic blood pressure, lower CVR was associated with higher white matter hyperintensity volume, Fazekas score and perivascular space counts. Lower CVR was associated with higher pulsatility of blood flow in the superior sagittal sinus and lower CSF flow stroke volume at the foramen magnum. Cilostazol and isosorbide mononitrate increased CVR in white matter. The CVR, intra-cranial flow and pulsatility techniques, alongside blood brain barrier permeability and microstructural integrity imaging were successfully employed in a multi-centre observational study. A clinical trial assessing the effects of drugs targeting blood pressure variability is nearing completion.
DISCUSSION:
Cerebrovascular dysfunction in SVD has been confirmed and may play a more direct role in disease pathogenesis than previously established risk factors. Advanced imaging measures assessing cerebrovascular dysfunction are feasible in multi-centre studies and trials. Identifying drugs that improve cerebrovascular dysfunction using these techniques may be useful in selecting candidates for definitive clinical trials which require large sample sizes and long follow up periods to show improvement against outcomes of stroke and dementia incidence and cognitive function
Pandemic Protagonists: Viral (Re)Actions in Pandemic and Corona Fictions
During the first mandatory lockdowns of the Covid-19 pandemic, citizens worldwide turned to "pandemic fictions" or started to produce their own »Corona Fictions« across different media. These accounts of (previously) experienced or imagined health crises feature a great variety of protagonists and their (re)actions in response to the exceptional circumstances. The contributors to this volume take a closer look at different pandemic protagonists in fictional narratives relating to the Covid-19 pandemic as well as in existing pandemic fictions. Thereby they provide new insights into pandemic narratives from a cultural, literary, and media studies perspective from antiquity to today
Graphonomics and your Brain on Art, Creativity and Innovation : Proceedings of the 19th International Graphonomics Conference (IGS 2019 â Your Brain on Art)
[Italiano]: âGrafonomia e cervello su arte, creativitĂ e innovazioneâ.
Un forum internazionale per discutere sui recenti progressi nell'interazione tra arti creative, neuroscienze, ingegneria, comunicazione, tecnologia, industria, istruzione, design, applicazioni forensi e mediche. I contributi hanno esaminato lo stato dell'arte, identificando sfide e opportunitĂ , e hanno delineato le possibili linee di sviluppo di questo settore di ricerca. I temi affrontati includono: strategie integrate per la comprensione dei sistemi neurali, affettivi e cognitivi in ambienti realistici e complessi; individualitĂ e differenziazione dal punto di vista neurale e comportamentale; neuroaesthetics (uso delle neuroscienze per spiegare e comprendere le esperienze estetiche a livello neurologico); creativitĂ e innovazione; neuro-ingegneria e arte ispirata dal cervello, creativitĂ e uso di dispositivi di mobile brain-body imaging (MoBI) indossabili; terapia basata su arte creativa; apprendimento informale; formazione; applicazioni forensi. / [English]: âGraphonomics and your brain on art, creativity and innovationâ.
A single track, international forum for discussion on recent advances at the intersection of the creative arts, neuroscience, engineering, media, technology, industry, education, design, forensics, and medicine.
The contributions reviewed the state of the art, identified challenges and opportunities and created a roadmap for the field of graphonomics and your brain on art.
The topics addressed include: integrative strategies for understanding neural, affective and cognitive systems in realistic, complex environments; neural and behavioral individuality and variation; neuroaesthetics (the use of neuroscience to explain and understand the aesthetic experiences at the neurological level); creativity and innovation; neuroengineering and brain-inspired art, creative concepts and wearable mobile brain-body imaging (MoBI) designs; creative art therapy; informal learning; education; forensics
Audiovisual speech perception in cochlear implant patients
Hearing with a cochlear implant (CI) is very different compared to a normal-hearing (NH) experience, as the CI can only provide limited auditory input. Nevertheless, the central auditory system is capable of learning how to interpret such limited auditory input such that it can extract meaningful information within a few months after
implant switch-on. The capacity of the auditory cortex to adapt to new auditory stimuli is an example of intra-modal plasticity â changes within a sensory cortical region as a result of altered statistics of the respective sensory input. However, hearing deprivation before implantation and restoration of hearing capacities after implantation can also induce cross-modal plasticity â changes within a sensory cortical region as a result of altered statistics of a different sensory input. Thereby, a preserved cortical region can, for example, support a deprived cortical region, as in the case of CI users which have been shown to exhibit cross-modal visual-cortex activation for purely auditory stimuli. Before implantation, during the period of hearing deprivation, CI users typically rely on additional visual cues like lip-movements for understanding speech. Therefore, it has been suggested that CI users show a pronounced binding of the auditory and visual systems, which may allow them to integrate auditory and visual speech information more efficiently. The projects included in this thesis investigate auditory, and particularly audiovisual speech processing in CI users. Four event-related potential (ERP) studies approach the matter from different perspectives, each with a distinct focus.
The first project investigates how audiovisually presented syllables are processed by CI users with bilateral hearing loss compared to NH controls. Previous ERP studies employing non-linguistic stimuli and studies using different neuroimaging techniques found distinct audiovisual interactions in CI users. However, the precise timecourse
of cross-modal visual-cortex recruitment and enhanced audiovisual interaction for speech related stimuli is unknown. With our ERP study we fill this gap, and we present differences in the timecourse of audiovisual interactions as well as in cortical source configurations between CI users and NH controls.
The second study focuses on auditory processing in single-sided deaf (SSD) CI users. SSD CI patients experience a maximally asymmetric hearing condition, as they have a CI on one ear and a contralateral NH ear. Despite the intact ear, several behavioural studies have demonstrated a variety of beneficial effects of restoring binaural hearing, but there are only few ERP studies which investigate auditory processing in SSD CI users. Our study investigates whether the side of implantation affects auditory processing and whether auditory processing via the NH ear of SSD CI users works similarly as in NH controls.
Given the distinct hearing conditions of SSD CI users, the question arises whether there are any quantifiable differences between CI user with unilateral hearing loss and bilateral hearing loss. In general, ERP studies on SSD CI users are rather scarce, and there is no study on audiovisual processing in particular. Furthermore, there are no reports on lip-reading abilities of SSD CI users. To this end, in the third project we extend the first study by including SSD CI users as a third experimental group. The study discusses both differences and similarities between CI users with bilateral hearing loss and CI users with unilateral hearing loss as well as NH controls and provides â for the first time â insights into audiovisual interactions in SSD CI users.
The fourth project investigates the influence of background noise on audiovisual interactions in CI users and whether a noise-reduction algorithm can modulate these interactions. It is known that in environments with competing background noise listeners generally rely more strongly on visual cues for understanding speech and that such situations are particularly difficult for CI users. As shown in previous auditory behavioural studies, the recently introduced noise-reduction algorithm "ForwardFocus" can be a useful aid in such cases. However, the questions whether employing the algorithm is beneficial in audiovisual conditions as well and whether using the algorithm has a measurable effect on cortical processing have not been investigated yet. In this ERP study, we address these questions with an auditory and audiovisual syllable discrimination task.
Taken together, the projects included in this thesis contribute to a better understanding of auditory and especially audiovisual speech processing in CI users, revealing distinct processing strategies employed to overcome the limited input provided by a CI. The results have clinical implications, as they suggest that clinical hearing assessments, which are currently purely auditory, should be extended to audiovisual assessments. Furthermore, they imply that rehabilitation including audiovisual training methods may be beneficial for all CI user groups for quickly achieving the most effective CI implantation outcome
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