75 research outputs found

    Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

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    Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (AÎČ), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, AÎČ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP)

    Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI

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    Background: Fibrosis, which is characterized by the pathological accumulation of collagen, is recognized as an important feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methods for the early diagnosis and follow-up of fibrosis in various disorders. Collagen targeting molecules are therefore of interest for potential in vivo imaging of fibrosis. In this study, we developed a collagen-specific probe using a new approach that takes advantage of the inherent specificity of Glycoprotein VI (GPVI), the main platelet receptor for collagens I and III. Methodology/Principal: Findings An anti-GPVI antibody that neutralizes collagen-binding was used to screen a bacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin) was synthesized. Solid-phase binding assays and histochemical analysis showed that collagelin specifically bound to collagen (Kd 10−7 M) in vitro, and labelled collagen fibers ex vivo on sections of rat aorta and rat tail. Collagelin is therefore a new specific probe for collagen. The suitability of collagelin as an in vivo probe was tested in a rat model of healed myocardial infarctions (MI). Injecting Tc-99m-labelled collagelin and scintigraphic imaging showed that uptake of the probe occurred in the cardiac area of rats with MI, but not in controls. Post mortem autoradiography and histological analysis of heart sections showed that the labeled areas coincided with fibrosis. Scintigraphic molecular imaging with collagelin provides high resolution, and good contrast between the fibrotic scars and healthy tissues. The capacity of collagelin to image fibrosis in vivo was confirmed in a mouse model of lung fibrosis. Conclusion/Significance: Collagelin is a new collagen-targeting agent which may be useful for non-invasive detection of fibrosis in a broad spectrum of diseases.Psycholog

    Inside the Black Box: A Narrative Review on Comprehensive Geriatric Assessment-Driven Interventions in Older Adults with Cancer

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    International audienceThere is a consensus that the use of comprehensive geriatric assessment (CGA) is good clinical practice for older patients with solid tumors or hematological malignancies. To be complete, a CGA must include a geriatric assessment and an intervention plan. According to the SIOG consensus, a CGA should assess several domains: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and the presence of geriatric syndromes. Progress has been made in the definition of the best way to detect problems, but the benefits are mostly based on prognosis stratification and on the adaptation of cancer treatment. The present review aims to evaluate the level of evidence regarding geriatric interventions proposed following the detection of a problem in cancer patients in each domain mentioned in the SIOG consensus. An online search of the PubMed database was performed using predefined search algorithms specific for each domain of the CGA. Eligible articles had to have well-defined interventions targeting specific domains of the CGA. We screened 1864 articles, but only a few trials on single-domain interventions were found, and often, these studies involved small groups of patients. This review highlights the scarcity of published studies on this topic. The specific impacts of CGA-based interventions have not yet been demonstrated. Multi-domain interventions seem promising, especially when they are based on global assessments. However, standardization seems difficult considering the lack of evidence for each domain. New studies are necessary in multiple care contexts, and innovative designs must be used to balance internal and external validity. An accurate description of the intervention and what “usual care” means will improve the external validity of such studies. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

    Geriatric Choosing Wisely choice of recommendations in France: a pragmatic approach based on clinical audits

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    International audienceBackground The international Choosing Wisely campaign seeks to improve the appropriateness of care, notably through large campaigns among physicians and users designed to raise awareness of the risks inherent in overmedication. Methods In deploying the Choosing Wisely campaign, the French Society of Geriatrics and Gerontology chose early operationalization via a tool for clinical audit over a limited area before progressive dissemination. This enabled validation of four consensual recommendations concerning the management of urinary tract infections, the prolonged use of anxiolytics, the use of neuroleptics in dementia syndromes, and the use of statins in primary prevention. The fifth recommendation concerns the importance of a dialogue on the level of care. It was written by patient representatives directly involved in the campaign. Results The first cross-regional campaign in France involved 5337 chart screenings in 43 health facilities. Analysis of the results showed an important variability in practices between institutions and significant percentage of inappropriate prescriptions, notably of psychotropic medication. Discussion The high rate of participation of target institutions shows that geriatrics professionals are interested in the evaluation and optimization of professional practices. Frequent overuse of psychotropic medication highlights the need of campaigns to raise awareness and encourage deprescribing
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