5,005 research outputs found

    Undergraduate Catalog of Studies, 2023-2024

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    Systemic function impairment and neurodegeneration in the general population

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    Advanced glycation end products and age-related diseases in the general population

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    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

    Using Image Translation To Synthesize Amyloid Beta From Structural MRI

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    Amyloid-beta and brain atrophy are known hallmarks of Alzheimer’s Disease (AD) and can be quantified with positron emission tomography (PET) and structural magnetic resonance imaging (MRI), respectively. PET uses radiotracers that bind to amyloid-beta, whereas MRI can measure brain morphology. PET scans have limitations including cost, invasiveness (involve injections and ionizing radiation exposure), and have limited accessibility, making PET not practical for screening early-onset AD. Conversely, MRI is a cheaper, less-invasive (free from ionizing radiation), and is more widely available, however, it cannot provide the necessary molecular information. There is a known relationship between amyloid-beta and brain atrophy. This thesis aims to synthesize amyloid-beta PET images from structural MRI using image translation, an advanced form of machine learning. The developed models have reported high-similarity metrics between the real and synthetic PET images and high-degree of accuracy in radiotracer quantification. The results are highly impactful as it enables amyloid-beta measurements form every MRI, for free

    Advanced glycation end products and age-related diseases in the general population

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    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

    Combined Nutrition and Exercise Interventions in Community Groups

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    Diet and physical activity are two key modifiable lifestyle factors that influence health across the lifespan (prevention and management of chronic diseases and reduction of the risk of premature death through several biological mechanisms). Community-based interventions contribute to public health, as they have the potential to reach high population-level impact, through the focus on groups that share a common culture or identity in their natural living environment. While the health benefits of a balanced diet and regular physical activity are commonly studied separately, interventions that combine these two lifestyle factors have the potential to induce greater benefits in community groups rather than strategies focusing only on one or the other. Thus, this Special Issue entitled “Combined Nutrition and Exercise Interventions in Community Groups” is comprised of manuscripts that highlight this combined approach (balanced diet and regular physical activity) in community settings. The contributors to this Special Issue are well-recognized professionals in complementary fields such as education, public health, nutrition, and exercise. This Special Issue highlights the latest research regarding combined nutrition and exercise interventions among different community groups and includes research articles developed through five continents (Africa, Asia, America, Europe and Oceania), as well as reviews and systematic reviews

    3D Innovations in Personalized Surgery

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    Current practice involves the use of 3D surgical planning and patient-specific solutions in multiple surgical areas of expertise. Patient-specific solutions have been endorsed for several years in numerous publications due to their associated benefits around accuracy, safety, and predictability of surgical outcome. The basis of 3D surgical planning is the use of high-quality medical images (e.g., CT, MRI, or PET-scans). The translation from 3D digital planning toward surgical applications was developed hand in hand with a rise in 3D printing applications of multiple biocompatible materials. These technical aspects of medical care require engineers’ or technical physicians’ expertise for optimal safe and effective implementation in daily clinical routines.The aim and scope of this Special Issue is high-tech solutions in personalized surgery, based on 3D technology and, more specifically, bone-related surgery. Full-papers or highly innovative technical notes or (systematic) reviews that relate to innovative personalized surgery are invited. This can include optimization of imaging for 3D VSP, optimization of 3D VSP workflow and its translation toward the surgical procedure, or optimization of personalized implants or devices in relation to bone surgery

    Metales y genes relacionados con el estrés oxidativo, factores metabólicos y variables relacionadas con la fragilidad ósea: un enfoque epidemiológico integrador

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina Preventiva y Salud Pública y Microbiología. Fecha de Lectura: 10-01-202

    Libro de Abstracts | VIII Jornadas de Investigación y Doctorado: “Ética en la Investigación Científica”

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    El objetivo de estas Jornadas es promover el intercambio científico entre estudiantes de doctorado, fomentando la participación, el debate y la discusión, de aspectos científicos tan importantes como la ética de la investigación. Para poner en valor el papel de los doctores en la sociedad, no podemos pasar por alto las competencias transversales que estos deben adquirir en su formación como doctores. Si bien la ética es algo fundamental en todas las facetas de la vida, en el caso de los investigadores cobra especial relevancia, ya que son generadores de conocimiento sobre el que se asentarán futuros desarrollos y políticas de interés para toda la sociedad. Por lo tanto, con el fin de incrementar la proyección social de las investigaciones llevadas a cabo y la proyección profesional de los doctores, es importante incidir en su formación ética. La base de la investigación académica está construida sobre la confianza. Los investigadores confían en que los resultados informados por otros son veraces. La sociedad confía en que los resultados de la investigación reflejan un intento honesto por parte de los científicos de describir el mundo de forma precisa. Pero esta confianza sólo perdurará si la comunidad científica transmite los valores asociados a la conducta de la ética de investigación. Por este motivo, la Universidad juega un papel muy importante en la formación de los doctores en cuestiones éticas que son inherentes al método científico y a la generación de conocimiento. Dentro de las universidades, las Escuelas Internacionales de Doctorado, con nuestros recursos, aptitudes y espacio de influencia, nos convertimos en actores clave para promover actitudes éticas entre los doctorandos, y estas Jornadas son una oportunidad muy valiosa para tratar este tema. Las ramas de conocimiento que se incluyen para estas Jornadas son las derivadas de los programas de doctorado de la EIDUCAM: -Ciencias de la Salud -Tecnologías de la Computación e Ingeniería Ambiental -Ciencias Sociales -Ciencias del DeporteActividad Física y DeporteAdministración y Dirección de EmpresasAgricultura y VeterinariaArte y HumanidadesCiencias AmbientalesCiencias de la AlimentaciónCiencias de la ComunicaciónCiencias ReligiosasDerechoEducaciónEnfermeríaFarmaciaIdiomasIngeniería, Industria y ConstrucciónMedicinaOdontologíaPodologíaPsicologíaTerapia y RehabilitaciónTurism

    Synthesis of multifunctional glyco-pseudodendrimers and glyco-dendrimers and their investigation as anti-Alzheimer agents

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    As the world population is aging, the cases of Alzheimer’s Disease (AD) are increasing. AD is a disorder of the brain which is characterized by the aggregation of amyloid beta (Aβ) plaques. This leads to the death of numerous brain cells thus affecting the cognitive and motor functions of the individual. Till date, no cure for the disease is available. Aβ are peptides with 40/42 amino acid residues but, their exact mechanism(s) of action in AD is under debate. Having different amino acid residues makes them susceptible to form hydrogen bonds. Dendrimers with sugar units are often referred to as glycopolymers and have been shown to have potential anti-amyloidogenic activity. However, they also have drawbacks, the synthesis involves multiple tedious steps, and dendrimers themselves offer only a limited number of functional units. Pseudodendrimers are another class of branched polymers based on hyperbranched polymers. Unlike the dendrimers, they are easy to synthesize with a dense shell of functional units on the surface. One of the main goals in this dissertation is the synthesis and characterization of pseudodendrimers and dendrimers based on 2,2-bis(hydroxymethyl)-propionic acid (bis-MPA), an aliphatic polyester scaffold, as it offers biocompatibility and easy degradability. Furthermore, they are decorated with mannose units on the surface using a ‘click’ reaction forming glyco-pseudodendrimers and glyco-dendrimers. A detailed characterization of their structures and physical properties was undertaken using techniques such as size exclusion chromatography, asymmetric flow field flow fractionation (AF4), and dynamic light scattering. The second main focus of this work has been to investigate the interaction of synthesized glyco-pseudodendrimers and glyco-dendrimers with Aβ 40 peptides. For this task, five different concentrations of the synthesized glycopolymers were tested with Aβ 40 using the Thioflavin T assay. The results of the synthesized polymers which produced the best results of showing maximum anti-aggregation behavior against Aβ 40 were confirmed with circular dichroism spectroscopy. AF4 was also used to investigate Aβ 40-glycopolymer aggregates, which has never been done before and constitutes the highlight of this dissertation. Atomic force microscopy was used to image Aβ 40-glycopseudodenrimer aggregates. A basic but important step in the development of drug delivery platforms is to evaluate the toxicity of the drugs synthesized. In this work, preliminary studies of the cytotoxicity of glyco-pseudodendrimers were performed in two different cell lines. Thus, this study comprises a preliminary investigation of the anti-amyloidogenic activity of glyco-pseudodendrimers synthesized on an aliphatic polyester backbone.:Abstract List of Tables List of Figures Abbreviations 1 Introduction 1.1 Objectives of the work 1.2 Thesis overview 2 Fundamentals and Literature 2.1 Alzheimer’s Disease and its impact 2.1.1 Neurological diagnosis of AD 2.1.2 Histopathology of AD 2.1.3 Amyloid precursor protein (APP) and its role in AD 2.2. Amyloid Beta (Aβ) peptide 2.2.1 Aβ peptide 2.2.2. Location and function 2.2.3 Amyloid hypothesis 2.2.4 The mechanism of Aβ aggregation 2.2.5 Amyloid fibrils 2.2.6 Toxicity of Aβ 2.3 Research methods to study Aβ aggregates 2.3.1 Models to study the mode of action of aggregates 2.3.2 Endogenous Aβ aggregates and synthetic aggregates 2.3.3 Strategies to alter aggregation of amyloids 2.4 Treatment and therapeutics 2.4.1 Current therapeutics 2.4.2 Current therapeutic research 2.4.2.1 Reduction of Aβ production 2.4.2.2 Reduction of Aβ plaque accumulation 2.4.2.2.1 Anti-amyloid aggregation agents 2.4.2.2.2 Metals 2.4.2.2.3 Immunotherapy 2.4.2.2.4 Dendrimers as potential anti-amyloidogenic agent 2.6 Dendrimers 2.6.1 Definition 2.6.2 Structure Table of Contents 2.6.3 Synthesis 2.6.4 Properties 2.7 Pseudodendrimers - a sub-class of hyperbranched polymer 2.7.1 Definition 2.7.2 Structure 2.7.3 Synthesis 3 Analytical Techniques 3.1 Size Exclusion Chromatography Coupled to Light Scattering (SEC-MALS) 3.2 Asymmetric Flow Field Flow Fractionation (AF4) 3.3 Dynamic Light Scattering 3.4 Molecular Dynamics Simulation 3.5 Nuclear Magnetic Resonance Spectroscopy 3.6 Thioflavin T fluorescence 3.6.1 Kinetic analysis 3.7 Circular Dichroism Spectroscopy 3.8 Atomic Force Microscopy 3.9 Cytotoxic assay 3.9.1 MTT assay 3.9.2 Determining the level of reactive oxygen species 3.9.3 Changes in mitochondrial transmembrane potential 3.9.4 Flow cytometric detection of phosphatidyl serine exposure 4 Experimental Details and Methodology 4.1 Details of chemicals/components used 4.1.1 Other materials 4.1.2 Peptide preparation 4.1.3 Buffer preparation 4.1.4 Fibril growth conditions 4.2 Synthesis and characterization of polymers 4.2.1 Synthesis and characterization of pseudodendrimers and dendrimers 4.2.1.1 Synthesis of hyperbranched polymer (1) 4.2.1.2 Synthesis of protected monomer 4.2.1.2.1 bis-MPA acetonide (2) 4.2.1.2.2 bis-MPA-acetonide anhydride (3) 4.2.1.3 Synthesis of protected pseudodendrimers (4, 6 and 8) and protected dendrimers (10, 12, and 14) 4.2.1.4 Deprotection of pseudodendrimers (5,7, and 9) and dendrimers (11,13 and 15) 4.2.2 Synthesis of glyco-pseudodendrimers and glyco-dendrimers 4.2.2.1 Pentynoic anhydride (16) 4.2.2.2 Synthesis of pentinate modified pseudodendrimers (17, 18 and 19) and dendrimers (20, 21 and 22) 4.2.2.3 3-Azido-1-propanol (23) 4.2.2.4 Mannose propyl azide tetraacetate (24) Table of Contents 4.2.2.5 Mannosepropylazide (25) 4.2.2.6 Glyco-pseudodendrimers (Gl-P) (26, 27 and 28) and glyco- dendrimers (Gl-D) (29, 30 and 31) 4.3 Analytical techniques and their general details 4.3.1 SEC-MALS - Instrumentation, software and analysis 4.3.2 AF4 - Instrumentation, software and analysis 4.3.2.1 Sample preparation 4.3.2.2 Method development for analysis of Gl-P and Gl-D 4.3.2.3 Method development for analysis of Aβ 40 and its interaction with Gl-P and Gl-D 4.3.3 Batch DLS - Instrumentation, software and analysis 4.3.3.1 Sample preparation 4.3.4 Theoretical calculations and molecular dynamics simulations 4.3.4.1 Ab-initio calculations 4.3.4.2 Modelling of the polymer structures 4.3.4.2.1 Pseudodendrimers 4.3.4.2.2 Dendrimers 4.3.4.2.3 Modification of the polymers with special end groups 4.3.4.2.4 Preparing of the THF solvent box 4.3.4.2.5 Solvation of the polymer structures 4.3.4.3 Molecular dynamics simulations 4.3.4.3.1 Evaluation of the simulation trajectories 4.4 Investigation of interaction of Gl-P and Gl-D with amyloid beta (Aβ 40) 4.4.1 ThT Assay - Instrumentation and software 4.4.1.1 Sample preparation 4.4.1.2 Kinetics based on ThT assay- software and data analysis 4.4.2 CD spectroscopy - Instrumentation and software 4.4.2.1 Sample preparation 4.4.3 AFM - Instrumentation and software 4.4.3.1 Substrate and sample preparation 4.4.3.2 Height determination and counting procedures 4.4.3.3 Topography and diameter 4.5 Cytotoxicity 4.5.1 Zeta potential 4.5.2 Cell culturing 4.5.3 Sample preparation 4.5.4 MTT assay 4.5.5 Changes in mitochondrial transmembrane potential (JC-1 method) 4.5.6 Flow cytometric detection of phosphatidyl serine exposure (Annexin V and PI method) 5 Results and Discussion 5.1 Synthesis and characterization of glyco-pseudodendrimers and glyco- dendrimers 5.1.1 Synthesis and characterization of hyperbranched polyester Table of Contents 5.1.2 Synthesis and characterization of pseudodendrimers P-G1-OH, P-G2-OH and P-G3-OH 5.1.3 Synthesis and characterization of dendrimers D-G4-OH, D-G5-OH and D-G6-OH 5.1.4 Synthesis and characterization of Gl-P and Gl-D 5.1.4.1 Molecular size determination of Gl-P and Gl-D using SEC 5.1.4.2 Particle size determination using batch DLS 5.1.4.3 Apparent densities 5.1.4.4 Molecular size determination of Gl-P and Gl-D using AF4 ..... 5.1.5 Molecular dynamics simulation 5.2 Investigation of interaction of Gl-P and Gl-D with amyloid beta (Aβ 40) ...... 5.2.1 ThT Assay 5.2.1.1 Kinetics based on ThT assay 5.2.2 CD spectroscopy 5.2.3 Time dependent AF4 5.3.2.1 Separation of Aβ 40 by AF4 5.3.2.2 Aβ 40 amyloid aggregation in the presence of Gl-P and Gl-D 5.2.4 AFM 5.2.4.1 Height 5.2.4.2 Topography and diameter 5.2.4.3 Length 5.2.4.4 Morphology 5.2.5 Cytotoxicity 5.2.5.1 MTT assay 5.2.5.2 Changes in mitochondrial transmembrane potential 5.2.5.3 Flow cytometric detection of phosphatidyl serine exposure 6 Conclusions and Outlook 7 Bibliography Appendix Acknowledgement
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