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Purpose: The tau tracer [F]AV1451, also known as flortaucipir, is a promising ligand for imaging tau accumulation in Alzheimer's disease (AD). Most of the previous studies have quantified tau load using standardized uptake value ratios (SUVr) derived from a static [F]AV1451 scan. SUVr may, however, be flow dependent and, especially for longitudinal studies, should be validated against a fully quantitative approach. The objective of this study was to identify the optimal tracer kinetic model for measuring tau load using [F]AV1451.
Procedures: Following intravenous injection of 225 ± 16 MBq [F]AV1451, 130 min dynamic PET scans were performed in five biomarker confirmed AD patients and five controls. Arterial blood sampling was performed to obtain a metabolite-corrected plasma input function. Next, regional time-activity curves were generated using PVElab software. These curves were analysed using several pharmacokinetic models.
Results: The reversible single tissue compartment model (1T2k_V) was the preferred model for all but one control. For AD patients, however, model preference shifted towards a reversible two tissue compartmental model (2T4k_V). The simplified reference tissue model (SRTM) derived binding potential (BP) showed good correlation (AD: r = 0.87, slope = 1.06; controls: r = 0.87, slope = 0.86) with indirect plasma input binding (distribution volume ratio-1). Standardized uptake value ratios (80-100 min) correlated well with DVR (r = 0.93, slope = 1.07) and SRTM-derived BP (r = 0.84, slope = 0.95). In addition, regional differences in tracer binding between subject groups in different tau-specific regions were observed.
Conclusions: Model preference of [F]AV1451 appears to depend on subject status and, in particular, V. The relationship between model preference and V suggests that (higher) tau load may be reflected by a second tissue compartment. Nevertheless, consistent results can be obtained using a 2T4k_V model. In addition, SRTM can be used to derive BP.
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http://dx.doi.org/10.1007/s11307-017-1080-z | DOI Listing |
Free Neuropathol
January 2025
Department of Laboratory Medicine, St. Michael's Hospital, Unity Health & Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
There is considerable evidence for a role for metabolic dysregulation, including disordered purine nucleotide metabolism, in the pathogenesis of Alzheimer's disease (AD). Purine nucleotide synthesis in the brain is regulated with high fidelity to co-ordinate supply with demand. The assembly of some purine biosynthetic enzymes into linear filamentous aggregates called "cytoophidia" (Gk.
View Article and Find Full Text PDFCureus
February 2025
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, JPN.
We report the case of a 44-year-old male patient without a notable medical history who developed transient osteoporosis following surgery for a medial malleolus fracture, which led to a stress fracture and osteonecrosis, ultimately requiring total talar replacement. The patient sustained the fracture spraining his ankle while welding. Osteosynthesis was performed using two cannulated cancellous screws, whereas bone union was achieved 3.
View Article and Find Full Text PDFVaccine
March 2025
Yokohama R&D Center, JNC Corporation, 5-1 Ookawa, Kanazawa-ku, Yokohama-shi Kanagawa, 236-8605, Japan. Electronic address:
Traditional virus chromatographic purification face limitations owing to the small pore sizes of conventional resins, which restrict efficient virus binding. The newly developed MLP1000 DexS, a cellulose monolith-like particle (MLP) with large continuous pores (radius of 1.5 μm) and a sulfate pseudo-affinity ligand, facilitates virus access to intraparticle surfaces and significantly enhances binding capacity.
View Article and Find Full Text PDFAlzheimers Dement (Amst)
February 2025
Institute of Psychiatry, Psychology & Neuroscience at King's College London London UK.
Introduction: Whether temporal proximity to parental onset of dementia (PPO) can be used to estimate timing of the preclinical stage of sporadic Alzheimer's disease (AD) remains uncertain.
Methods: We investigated cross-sectionally adults aged > 50 without dementia included in the European Prevention of Alzheimer's Dementia (EPAD) study. PPO was tested as a predictor of quantitative levels of cerebrospinal fluid (CSF) β-amyloid (1-42) (Aβ1-42) in those with a parental history of dementia ( = 688) and of phosphorylated tau (p-tau) and EPAD neuropsychological examination (ENE) subscores in an amyloid positive subgroup ( = 226).
J Biomed Mater Res B Appl Biomater
March 2025
Departamento de Prótese e Periodontia da Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia de Piracicaba (FOP), Piracicaba, São Paulo, Brazil.
This study evaluated the reliability, failure mode, and stress distribution of wide-diameter extra-short dental implants (ESDI) as support for single crowns (SC) and fixed partial dentures (FPD) (3:1 crown-to-implant ratio [C:I]) for rehabilitation in the posterior atrophic mandible. For that, 126 ESDI (of 5 mm length) were allocated in four groups based on diameter (Ø4 and Ø6 mm) and prostheses (SC and FPD): SC4, SC6, FPD4, and FPD6. The fatigue test was performed by step-stress accelerated life testing (n = 21/group), failure mode by fractographic analysis, and stress distribution by finite element analysis: von Mises stress (σ), maximum shear stress (τ), and minimum principal stress (σ).
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