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Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.
J Prev Alzheimers Dis
January 2025
Alzheimer's Drug Discovery Foundation, New York, NY, USA. Electronic address:
There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.
View Article and Find Full Text PDFBlood-brain barrier water permeability across the adult lifespan: A multi-echo ASL study.
Neurobiol Aging
January 2025
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
An emerging biomarker of blood-brain barrier (BBB) permeability is the time of exchange (Tex) of water from the blood to tissue, as measured by multi-echo arterial spin labeling (ASL) MRI. This new non-invasive sequence, already tested in mice, has recently been adapted to humans and optimized for clinical scanning time. In this study, we studied the normal variability of Tex over age and sex, which needs to be established as a reference for studying changes in neurological disease.
View Article and Find Full Text PDFEndophenotype presentation of athletes with concussion contingent on sex and time since injury.
Brain Inj
January 2025
Department of Sports Medicine, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA.
Introduction: Athletes with concussions experience heterogeneous symptoms and clinical trajectories. Subclassification provides diagnostic clarity that may improve prognostication and individualized treatments.
Methods: We hypothesized that endophenotypes of adolescent athletes with concussions differ based on sex and time since injury.
A multi-level analysis of motor and behavioural dynamics in 9-month-old preterm and term-born infants during changing emotional and interactive contexts.
Sci Rep
January 2025
Strathclyde Institute of Education, University of Strathclyde, Lord Hope Building, Glasgow, G4 0LT, UK.
Computational analysis of infant movement has significant potential to reveal markers of developmental health. We report two studies employing dynamic analyses of motor kinematics and motor behaviours, which characterise movement at two levels, in 9-month-old infants. We investigate the effect of preterm birth (< 33 weeks of gestation) and the effect of changing emotional and social-interactive contexts in the still-face paradigm.
View Article and Find Full Text PDFLong-term Complications From Peripheral Nerve Blocks After Pediatric Orthopaedic Lower Extremity Procedures: A Systematic Review.
Am J Sports Med
January 2025
Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Orthopaedic Institute for Children, Los Angeles, California, USA; Boulder Medical Center, Boulder, Colorado, USA.
Article Synopsis
- Peripheral nerve blocks (PNBs) are commonly used in pediatric orthopedic surgery for pain management and quicker discharge, but they can lead to both short- and long-term complications.
- A systematic review identified 16 studies (10% of those reviewed) that discussed long-term complications following PNBs in pediatric patients, with 9 reporting issues such as chronic pain, motor deficits, and reduced range of motion.
- Overall, complications were noted in a small percentage of patients, with chronic pain occurring in 5%, strength deficits in 10%, and sensory deficits in just 0.07%.
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