81 research outputs found
The Impact of Registered Intermediary Presence on Adults’ Perceptions of Child Witnesses: Evidence from a Mock Cross Examination
Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimer's Disease
In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice
Role of Synucleins in Alzheimer’s Disease
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-β protein (Aβ) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of α-synuclein (α-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Aβ and Tau; however, recent studies suggest that α-syn might also play a role in the pathogenesis of AD. For example, fragments of α-syn can associate with amyloid plaques and Aβ promotes the aggregation of α-syn in vivo and worsens the deficits in α-syn tg mice. Moreover, α-syn has also been shown to accumulate in limbic regions in AD, Down’s syndrome, and familial AD cases. Aβ and α-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Aβ and α-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Aβ and α-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD
Simultaneous measurement and modulation of multiple physiological parameters in the isolated heart using optical techniques
Correction: Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.
[This corrects the article DOI: 10.1371/journal.pmed.1002352.]
Synthesis, characterization, and preclinical validation of a PET radiopharmaceutical for interrogating Aβ (β-amyloid) plaques in Alzheimer’s disease
Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and ca125 in predicting epithelial ovarian cancer: A meta-analysis
Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial
Non-technical Skills in Healthcare
AbstractNon-technical Skills (NTS) are a set of generic cognitive and social skills, exhibited by individuals and teams, that support technical skills when performing complex tasks. Typical NTS training topics include performance shaping factors, planning and preparation for complex tasks, situation awareness, perception of risk, decision-making, communication, teamwork and leadership. This chapter provides a framework for understanding these skills in theory and practice, how they interact, and how they have been applied in healthcare, as well as avenues for future research
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