247 research outputs found

    30th European Congress on Obesity (ECO 2023)

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    This is the abstract book of 30th European Congress on Obesity (ECO 2023

    Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

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    Publisher Copyright: © 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.In 2015, EFSA established a temporary tolerable daily intake (t-TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re-evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re-evaluation, a pre-established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.Peer reviewe

    Cognitive Decay And Memory Recall During Long Duration Spaceflight

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    This dissertation aims to advance the efficacy of Long-Duration Space Flight (LDSF) pre-flight and in-flight training programs, acknowledging existing knowledge gaps in NASA\u27s methodologies. The research\u27s objective is to optimize the cognitive workload of LDSF crew members, enhance their neurocognitive functionality, and provide more meaningful work experiences, particularly for Mars missions.The study addresses identified shortcomings in current training and learning strategies and simulation-based training systems, focusing on areas requiring quantitative measures for astronaut proficiency and training effectiveness assessment. The project centers on understanding cognitive decay and memory loss under LDSF-related stressors, seeking to establish when such cognitive decline exceeds acceptable performance levels throughout mission phases. The research acknowledges the limitations of creating a near-orbit environment due to resource constraints and the need to develop engaging tasks for test subjects. Nevertheless, it underscores the potential impact on future space mission training and other high-risk professions. The study further explores astronaut training complexities, the challenges encountered in LDSF missions, and the cognitive processes involved in such demanding environments. The research employs various cognitive and memory testing events, integrating neuroimaging techniques to understand cognition\u27s neural mechanisms and memory. It also explores Rasmussen\u27s S-R-K behaviors and Brain Network Theory’s (BNT) potential for measuring forgetting, cognition, and predicting training needs. The multidisciplinary approach of the study reinforces the importance of integrating insights from cognitive psychology, behavior analysis, and brain connectivity research. Research experiments were conducted at the University of North Dakota\u27s Integrated Lunar Mars Analog Habitat (ILMAH), gathering data from selected subjects via cognitive neuroscience tools and Electroencephalography (EEG) recordings to evaluate neurocognitive performance. The data analysis aimed to assess brain network activations during mentally demanding activities and compare EEG power spectra across various frequencies, latencies, and scalp locations. Despite facing certain challenges, including inadequacies of the current adapter boards leading to analysis failure, the study provides crucial lessons for future research endeavors. It highlights the need for swift adaptation, continual process refinement, and innovative solutions, like the redesign of adapter boards for high radio frequency noise environments, for the collection of high-quality EEG data. In conclusion, while the research did not reveal statistically significant differences between the experimental and control groups, it furnished valuable insights and underscored the need to optimize astronaut performance, well-being, and mission success. The study contributes to the ongoing evolution of training methodologies, with implications for future space exploration endeavors

    Cultivate Quantitative Magnetic Resonance Imaging Methods to Measure Markers of Health and Translate to Large Scale Cohort Studies

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    Magnetic Resonance Imaging (MRI) is an indispensable tool in healthcare and research, with a growing demand for its services. The appeal of MRI stems from its non-ionizing radiation nature, ability to generate high-resolution images of internal organs and structures without invasive procedures, and capacity to provide quantitative assessments of tissue properties such as ectopic fat, body composition, and organ volume. All without long term side effects. Nine published papers are submitted which show the cultivation of quantitative measures of ectopic fat within the liver and pancreas using MRI, and the process of validating whole-body composition and organ volume measurements. All these techniques have been translated into large-scale studies to improve health measurements in large population cohorts. Translating this work into large-scale studies, including the use of artificial intelligence, is included. Additionally, an evaluation accompanies these published studies, appraising the evolution of these quantitative MRI techniques from the conception to their application in large cohort studies. Finally, this appraisal provides a summary of future work on crowdsourcing of ground truth training data to facilitate its use in wider applications of artificial intelligence.In conclusion, this body of work presents a portfolio of evidence to fulfil the requirements of a PhD by published works at the University of Salford

    Genetic Conditions Affecting the Skeleton

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    In this Special Issue of Genes entitled “Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis”, evidence is presented that suggests that congenital, idiopathic scoliosis, and arthrogryposis share similar overlapping, but also distinct, etiopathogenic mechanisms, including connective tissue and neuromuscular mechanisms. Congenital scoliosis (CS) is defined by the presence of an abnormal spinal curvature, due to an underlying vertebral bony malformation (VM). Idiopathic scoliosis (IS) is defined by the presence of an abnormal structural spinal curvature of ≥10 degrees in the sagittal plane, in the absence of an underlying VM. Arthrogryposis is defined by the presence of congenital contractures in two or more joints of the appendicular skeleton. All three conditions have complex genetic causes. This Special Issue highlights the complex nature of these conditions and current concepts in our approach to better understand their genetics

    Left Ventricular Diastolic Function in Adolescents with Overweight and Obesity: The Moderating Influence of Physical Activity, Cardiorespiratory Fitness, and Metabolic Health

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    Lifelong preservation of left ventricular diastolic function (LVDF) is an important goal for reducing the burden of diastolic heart failure and related adverse health outcomes. LVDF is strongly linked with obesity. The global obesity pandemic has already increased the burden of diastolic heart failure in adults, but the prevalence of overweight and obesity is rising fastest in children, potentially setting them on a course to early heart disease. Public health measures designed to tackle the problem of adolescent obesity have focused on lifestyle interventions, such as exercise promotion and dietary improvements, with uncertain impact on LVDF. This thesis aimed to investigate how obesity, physical activity (PA) and innate cardiorespiratory fitness (CRF) influence LVDF in adolescents. From these data, it was also aimed to identify a PA target that might be sufficient to prevent adolescent impaired LVDF. To demonstrate the need for a focus on LVDF in this age group, Study 1 was a meta-analysis of the relationship of obesity with LVDF in adolescents. The results indicated that those with obesity were likely to have impaired LVDF and that such impairments were best demonstrated by septal tissue-Doppler imaging (TDI) methods of echocardiography (z-score difference=0.91; 95% CI=0.46, 1.37). This study also identified preliminary evidence for links of insulin resistance (IR) and CRF with LVDF, but there were no studies to address the relationship between PA and LVDF. Therefore, Study 2 leveraged data from 99 adolescents with either overweight/obesity or normal-weight and high PA (≥75th percentile) or low PA (≤25th percentile) to address this question. Vigorous physical activity (VPA) was the only PA intensity associated with LVDF, with the strongest links to septal TDI. Mediation analyses revealed that higher VPA had a direct benefit on LVDF as well as an indirect effect through decreased adiposity. This study also confirmed the link of IR and CRF with LVDF, independently from adiposity. As CRF was linked with LVDF and is a good measure of general cardiovascular health, Study 3 aimed to understand the intensity and duration of PA that are best associated with CRF in a large population of adolescents (n=339). Only VPA was associated with CRF, with relationships plateauing at around 20 minutes. This short duration of daily VPA contrasts with the World Health Organization’s moderate-to-vigorous PA guidelines, which can be satisfied by only undertaking moderate PA, with no apparent independent benefit on LVDF or CRF, suggesting that specific VPA guidelines for adolescent cardiovascular health are needed. This thesis provides novel insights into the effects of obesity and PA on LVDF in adolescents. A targeted approach, not simply focused on weight loss, has been identified, in theory, to prevent or reverse this adverse early phenotype and provides a roadmap for the duration of routine VPA that might be tested in a randomised, controlled clinical trial as a means to normalise LVDF

    Identification of molecular mechanisms underlying frailty and successful aging in centenarians

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    259 p.El envejecimiento es un proceso sistémico, multifactorial y degenerativo caracterizado por el declive y la pérdida de capacidades físicas y mentales. La esperanza media de vida ha aumentado considerablemente en el último siglo, incrementando así el número de personas mayores en la población y, por tanto, las limitaciones funcionales y las enfermedades relacionadas con la edad. En este sentido, la fragilidad representa un nuevo síndrome geriátrico que se caracteriza por una pérdida de la capacidad funcional y una disminución de la capacidad de respuesta al estrés fisiológico, lo que resulta en una mayor vulnerabilidad del individuo y en resultados negativos para la salud. Se trata de una afección dinámica que se está convirtiendo en un importante problema de salud que es necesario detectar e intervenir. Se sabe relativamente poco sobre la fisiopatología de este síndrome y los mecanismos moleculares subyacentes a la fragilidad siguen siendo poco conocidos. Con el fin de abordar esta cuestión, se analizó el perfil transcriptómico de un conjunto de individuos robustos y frágiles residentes en el País Vasco, y se encontraron 35 genes expresados diferencialmente que se asociaron con el estado e fragilidad. Éstos incluían genes asociados a inflamación, respuesta inmune o miRNAs, procesos previamente relacionados con la fragilidad. Entre ellos, 7 candidatos fueron validados en cohortes independientes y también mostraron un patrón de expresión similar en mioblastos y fibroblastos primarios humanos mantenidos en cultivo. Su expresión fue parcialmente restaurada tras diferentes programas de intervención en individuos frágiles. Análisis adicionales revelaron la expresión de un conjunto mínimo de 3 genes (aumento de EGR1 y disminución de DDX11L1 y miR454) fuertemente asociados con el estado de fragilidad y las características clínicas vinculadas a la fragilidad como la multimorbilidad y la polifarmacia. Además, descubrimos su papel en el envejecimiento celular e identificamos su actividad como mediadores de vías asociadas a la senescencia, convirtiéndose en potenciales actores en la fisiopatología de este síndrome geriátrico. En conjunto, nuestros resultados revelan un vínculo entre fragilidad y senescencia.El envejecimiento cerebral consiste en una pérdida progresiva de las capacidades funcionales que se asocia a un deterioro cognitivo progresivo y puede conducir a enfermedades neurodegenerativas.Aunque se han utilizado diferentes enfoques para identificar biomarcadores y vías moleculares subyacentes al envejecimiento cerebral, se mantienen en gran medida desconocidos. Los centenarios,muestran una longevidad extrema que se acompaña de una mejor función cognitiva, menos comorbilidades y una mayor calidad de vida y, por lo tanto, se han propuesto como modelo de envejecimiento saludable. En nuestro estudio, realizamos análisis transcriptómicos en muestras de hipocampo humano de individuos de diferentes edades, incluyendo individuos jóvenes, ancianos y centenarios, con el fin de abordar los mecanismos moleculares subyacentes al envejecimiento cerebral.Identificamos un patrón de expresión génica diferencial en muestras cerebrales de centenarios en comparación con los otros dos grupos. En particular, varios miembros de la familia de genes de las metalotioneínas (MTs) se expresaron en gran medida en el hipocampo de los centenarios. Estos hallazgos se validaron en dos cohortes adicionales e independientes. En particular, las MTs fueron expresadas principalmente por los astrocitos y estudios funcionales in vitro describieron el papel de las MTs en su viabilidad y actividad. De hecho, el silenciamiento de MT1 o MT3 en astrocitos humanos primarios provocó una disminución de la proliferación, un aumento de la apoptosis y la senescencia, junto con un incremento de la expresión de genes inflamatorios. En general, estos resultados muestran que el hipocampo de los centenarios presenta altos niveles de MTs, que se expresan principalmente en los astrocitos convirtiéndose en un mecanismo defensivo que podría proporcionar neuroprotección en el cerebro durante el envejecimiento. Otros análisis adicionales, revelaron un subconjunto de 6 genes cuya expresión se correlacionaba con el envejecimiento cronológico en el hipocampo humano. Entre ellos, el descenso de RAD23B mostró las mayores diferencias a nivel estadístico tanto en humanos como enratones. La validación en cohortes adicionales confirmó la disminución de los niveles de RAD23B con la edad, también a nivel proteico, que se agravaban en condiciones patológicas, ya que sus niveles eran más bajos o totalmente ausentes en pacientes con enfermedad de Alzheimer. Además, experimentos de silenciamiento en cultivos celulares in vitro demostraron que estaba implicado en la viabilidad y actividad de los astrocitos, lo que indica que es un biomarcador putativo y regulador del envejecimiento celular en el cerebro
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