molecular mechanisms in cognitive frailty potential therapeutic targets for oxygen ozone treatment

Abstract In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and metabolic alterations, mitochondria dysfunctions and slowdown in regenerative processes and immune system, with a complex and multifactorial aetiology. Although several treatments are available, challenges regarding the efficacy and the costs persist. Here, we proposed an alternative non-pharmacological, non-side-effect, low cost therapy based on anti-inflammation, antioxidant, regenerative and anti-pathogens properties of ozone (O3), through the activation of several molecular mechanisms (Nrf2-ARE, NF-κB, NFAT, AP-1, HIFα). We highlighted how these specific processes could be implicated in cognitive frailty to identify putative therapeutic targets for its treatment. The O2-O3 therapy has never been tested for cognitive frailty. This work provides thus wide scientific background to build a consistent rationale for testing for the first time this therapy, that could modulate the immune, inflammatory, oxidant, metabolic, endocrine, microbiota and regenerative processes impaired in cognitive frailty. Although insights are needed, the O2-O3 therapy could represent a faster, easier, inexpensive monodomain intervention, working in absence of side effects, for cognitive frailty

Échanges et circulation des textes dans l’espace littéraire mondial

Pascale Casanova Partant de la description de la structure et du fonctionnement de l’espace littéraire international, le séminaire a porté principalement, d’une part sur la question de la constitution et de la légitimation de la valeur littéraire et d’autre part sur l’hypothèse de l’établissement d’une « grammaire » des choix littéraires dans les zones les plus dépendantes de l’espace littéraire. C’est notamment à partir de la traduction considérée à la fois comme échange inégal, voie d’accum..

Biological markers of disease and disease progression in Alzheimer's disease: apolipoprotein E and regional atrophic changes of the brain

Dottorato di ricerca in neuroscienze. 10. ciclo. A.a. 1994-98Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

MRI-based automated computer classification of probable AD versus normal controls.

International audienceAutomated computer classification (ACC) techniques are needed to facilitate physician's diagnosis of complex diseases in individual patients. We provide an example of ACC using computational techniques within the context of cross-sectional analysis of magnetic resonance images (MRI) in neurodegenerative diseases, namely Alzheimer's dementia (AD). In this paper, the accuracy of our ACC methodology is assessed when presented with real life, imperfect data, i.e., cohorts of MRI with varying acquisition parameters and imaging quality. The comparative methodology uses the Jacobian determinants derived from dense deformation fields and scaled grey-level intensity from a selected volume of interest centered on the medial temporal lobe. The ACC performance is assessed in a series of leave-one-out experiments aimed at separating 75 probable AD and 75 age-matched normal controls. The resulting accuracy is 92% using a support vector machine classifier based on least squares optimization. Finally, it is shown in the Appendix that determinants and scaled grey-level intensity are appreciably more robust to varying parameters in validation studies using simulated data, when compared to raw intensities or grey/white matter volumes. The ability of cross-sectional MRI at detecting probable AD with high accuracy could have profound implications in the management of suspected AD candidates

Clinical characteristics of frontotemporal patients with symmetric brain atrophy

In this paper we explored patterns of frontal and temporal asymmetry in frontotemporal dementia (FTD) and tried to isolate clinical correlates associated with asymmetry or lack thereof. Volumes of frontal and temporal lobes, hippocampus and entorhinal cortex were measured using magnetic resonance imaging (MRI) in 10 patients with FTD. Age- and cranial size-specific values were computed through linear regression analysis (W-scores). A subgroup of 3 patients with symmetric frontal and temporal atrophy was identified. When compared to patients with asymmetric atrophy, the former had younger age at onset of the disease (p = 0.02), greater overall frontotemporal (p = 0.02) and greater entorhinal atrophy (p < 0.04). Two of the three patients were apolipoprotein E epsilon4 carriers versus none of the asymmetric patients (p = 0.02). The lack of asymmetry in this small sample of FTD patients was associated with greater brain atrophy, younger age at onset, and presence of the epsilon4 allele of apolipoprotein E. The presence of the epsilon4 allele is consistent with the hypothesis of greater vulnerability of the brain in epsilon4 carriers

Hippocampal and amygdalar local structural differences in elderly patients with schizophrenia

Morphological abnormalities have been reported for the hippocampi and amygdalae in young schizophrenia patients, but very little is known about the pattern of abnormalities in elderly schizophrenia patients. Here we investigated local structural differences in the hippocampi and amygdalae of elderly schizophrenia patients compared with healthy elderly subjects. We also related these differences to clinical symptom severity

The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia

To compare patterns of brain atrophy in fronto-temporal dementia (FTD) and Alzheimer's disease (AD) since atrophy in individual areas may not be sufficiently specific as diagnostic marker

miR-146a Plasma Levels Are Not Altered in Alzheimer's Disease but Correlate With Age and Illness Severity

miR-146a is a microRNA (miRNA) involved in neuroinflammation and aging; alterations in its expression were described in Alzheimer’s disease (AD). However, most of the studies conducted so far on this miRNA included a limited number of participants and produced contradictory results. We compared miR-146a levels in plasma from 33 AD patients vs. 28 age-matched non-affected controls (CTRL) through quantitative real-time polymerase chain reaction (qRT-PCR). No difference between the case and the control group was evidenced, but a correlation was detected between miR-146a levels and subjects’ age (p < 0.001) as well as between miR-146a levels and patients’ Mini-Mental State Examination (MMSE) scores (p = 0.011), in an enlarged group of 51 AD patients and 45 CTRL supporting a role for this miRNA in aging processes and disease progression