Lower Locus Coeruleus MRI intensity in patients with late-life major depression

Background: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. Methods: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. Results: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). Conclusion: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons

Model d'electrodinàmica i arrítmies en aurícula humana utilitzant paral·lelització en GPU: de cèl·lula a teixit

Atrial fibrillation is one of the most prevalent cardiac arrhythmias, specially among people over 65 years old. A good understanding of atrial electrophysiology is thus neccessary to be able to develop either pharmacological or electrical therapeutics to treat this arrhythmia.The goal of this project is to study instabilities in human atrial cardiac tissue using a complex non-linear set of differential equations through GPU parallel computing. More specifically, the topic it focuses on is atrial calcium alternans driven by SR Ca content fluctuations and SR refractoriness when extending the model from the cell level to tissue.El objetivo de este proyecto es estudiar inestabilidades en tejido de aurícula humana utilizando un conjunto de ecuaciones diferenciales no lineales y resolviéndolas paralelamente en GPU. Específicamente, se centra en analizar alternans en el calcio producidas por fluctuaciones en el SR y su periodo refractario cuando el modelo se extiende de célula a tejido.L'objectiu d'aquest projecte és estudiar inestabilitats en teixit d'aurícula humana utilitzant un conjunt d'equacions diferencials no lineals i resolent-les en GPU. Concretament, es focalitza en analitzar alternans en el calci produïdes per fluctuacions en el SR i pel seu període refractari quan el model s'extén de cèl·lula a teixit

Model d'electrodinàmica i arrítmies en aurícula humana utilitzant paral·lelització en GPU: de cèl·lula a teixit

Atrial fibrillation is one of the most prevalent cardiac arrhythmias, specially among people over 65 years old. A good understanding of atrial electrophysiology is thus neccessary to be able to develop either pharmacological or electrical therapeutics to treat this arrhythmia.The goal of this project is to study instabilities in human atrial cardiac tissue using a complex non-linear set of differential equations through GPU parallel computing. More specifically, the topic it focuses on is atrial calcium alternans driven by SR Ca content fluctuations and SR refractoriness when extending the model from the cell level to tissue.El objetivo de este proyecto es estudiar inestabilidades en tejido de aurícula humana utilizando un conjunto de ecuaciones diferenciales no lineales y resolviéndolas paralelamente en GPU. Específicamente, se centra en analizar alternans en el calcio producidas por fluctuaciones en el SR y su periodo refractario cuando el modelo se extiende de célula a tejido.L'objectiu d'aquest projecte és estudiar inestabilitats en teixit d'aurícula humana utilitzant un conjunt d'equacions diferencials no lineals i resolent-les en GPU. Concretament, es focalitza en analitzar alternans en el calci produïdes per fluctuacions en el SR i pel seu període refractari quan el model s'extén de cèl·lula a teixit

Model d'electrodinàmica i arrítmies en aurícula humana utilitzant paral·lelització en GPU: de cèl·lula a teixit

Atrial fibrillation is one of the most prevalent cardiac arrhythmias, specially among people over 65 years old. A good understanding of atrial electrophysiology is thus neccessary to be able to develop either pharmacological or electrical therapeutics to treat this arrhythmia.The goal of this project is to study instabilities in human atrial cardiac tissue using a complex non-linear set of differential equations through GPU parallel computing. More specifically, the topic it focuses on is atrial calcium alternans driven by SR Ca content fluctuations and SR refractoriness when extending the model from the cell level to tissue.El objetivo de este proyecto es estudiar inestabilidades en tejido de aurícula humana utilizando un conjunto de ecuaciones diferenciales no lineales y resolviéndolas paralelamente en GPU. Específicamente, se centra en analizar alternans en el calcio producidas por fluctuaciones en el SR y su periodo refractario cuando el modelo se extiende de célula a tejido.L'objectiu d'aquest projecte és estudiar inestabilitats en teixit d'aurícula humana utilitzant un conjunt d'equacions diferencials no lineals i resolent-les en GPU. Concretament, es focalitza en analitzar alternans en el calci produïdes per fluctuacions en el SR i pel seu període refractari quan el model s'extén de cèl·lula a teixit

Use of Enzymatically Converted Cell-Free DNA (cfDNA) Data for Copy Number Variation-Linked Fragmentation Analysis Allows for Early Colorectal Cancer Detection

The use of non-invasive liquid biopsy-based cell-free DNA (cfDNA) analysis is an emerging method of cancer detection and intervention. Different analytical methodologies are used to investigate cfDNA characteristics, resulting in costly and long analysis processes needed for combining different data. This study investigates the possibility of using cfDNA data converted for methylation analysis for combining the cfDNA fragment size with copy number variation (CNV) in the context of early colorectal cancer detection. Specifically, we focused on comparing enzymatically and bisulfite-converted data for evaluating cfDNA fragments belonging to chromosome 18. Chromosome 18 is often reported to be deleted in colorectal cancer. We used counts of short and medium cfDNA fragments of chromosome 18 and trained a linear model (LDA) on a set of 2959 regions to predict early-stage (I–IIA) colorectal cancer on an independent test set. In total, 87.5% sensitivity and 92% specificity were obtained on the enzymatically converted libraries. Repeating the same workflow on bisulfite-converted data yielded lower accuracy results with 58.3% sensitivity, implying that enzymatic conversion preserves the cancer fragmentation footprint in whole genome data better than bisulfite conversion. These results could serve as a promising new avenue for the early detection of colorectal cancer using fragmentation and methylation approaches on the same datasets

Lower Locus Coeruleus MRI intensity in patients with late-life major depression

Background: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. Methods: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. Results: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). Conclusion: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.Peer ReviewedObjectius de Desenvolupament Sostenible::9 - Indústria, Innovació i InfraestructuraObjectius de Desenvolupament Sostenible::4 - Educació de QualitatObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Lower Locus Coeruleus MRI intensity in patients with late-life major depression

The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons