Background: Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Quantitative real-time PCR (RT qPCR) is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB.
Introduction
Simulation forms a key element of undergraduate Radiography education as it enables students to develop their clinical skills in a safe environment. In this study, an immersive three-dimensional (3D) virtual radiography simulation tool was piloted in an undergraduate Radiography curriculum and user feedback retrieved.
Methods
The 3D virtual simulation tool by Virtual Medical Coaching Ltd was introduced to first year radiography students (n = 105). This technology guided students through a comprehensive process of learning anatomy, radiographic positioning and pathology. Students then X-rayed a virtual patient in the VR suite using HTC Vive Pro™ headsets and hand controllers. Instant feedback was provided. An online survey was later disseminated to students to gather user feedback. Thematic and descriptive statistical analyses were applied.
Results
A response rate of 79% (n = 83) was achieved. Most respondents (58%) reported enjoying VR simulation, whilst some felt indifferent towards it (27%). Ninety-four percent would recommend this tool to other students. The mean length of time it took for students to feel comfortable using the technology was 60 min (10–240 min). Most respondents (58%) desired more VR access. Students attributed enhanced confidence in the areas of beam collimation (75%), anatomical marker placement (63%), centring of the X-ray tube (64%) and exposure parameter selection (56%) to their VR practice. Many students (55%) advocated the use of VR in formative or low stakes assessments. Issues flagged included technical glitches, inability to palpate patient and lack of constructive feedback.
Conclusion
Student feedback indicates that 3D virtual radiography simulation is a valuable pedagogical tool in radiography education
Implications for practice
3D immersive VR simulation is perceived by radiography students to be a valuable learning resource. VR needs to be strategically implemented into curricula to maximise its benefits.
Aβ (β-amyloid) peptides are found aggregated in the cortical amyloid plaques associated with Alzheimer's disease neuropathology. Inhibition of the proteasome alters the amount of Aβ produced from APP (amyloid precursor protein) by various cell lines in vitro. Proteasome activity is altered during aging, a major risk factor for Alzheimer's disease. In the present study, a human neuroblastoma cell line expressing the C-terminal 100 residues of APP (SH-SY5Y-SPA4CT) was used to determine the effect of proteasome inhibition, by lactacystin and Bz-LLL-COCHO (benzoyl-Leu-Leu-Leu-glyoxal), on APP processing at the γ-secretase site. Proteasome inhibition caused a significant increase in Aβ peptide levels in medium conditioned by SH-SY5Y-SPA4CT cells, and was also associated with increased cell death. APP is a substrate of the apoptosis-associated caspase 3 protease, and we therefore investigated whether the increased Aβ levels could reflect caspase activation. We report that caspase activation was not required for proteasome-inhibitor-mediated effects on APP (SPA4CT) processing. Cleavage of Ac-DEVD-AMC (N-acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin), a caspase substrate, was reduced following exposure of SH-SY5Y-SPA4CT cells to lactacystin, and co-treatment of cells with lactacystin and a caspase inhibitor [Z-DEVD-FMK (benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone)] resulted in higher Aβ levels in medium, augmenting those seen with lactacystin alone. This study indicated that proteasome inhibition could increase APP processing specifically at the γ-secretase site, and increase release of Aβ, in the absence of caspase activation. This indicates that the decline in proteasome function associated with aging would contribute to increased Aβ levels.
Several lines of evidence indicate that the Aβ peptide is involved at some level in the pathological process that results in the clinical symptoms of AD (Alzheimer's disease). The N-terminus of Aβ is generated by cleavage of the Met-Asp bond at position 671-672 of APP (amyloid precursor protein), catalysed by a proteolytic activity called β-secretase. Two 'β-secretase' proteases have been identified: BACE (β-site APPcleaving enzyme) and BACE2. The cause of sporadic AD is currently unknown, but some studies have reported elevated BACE/β-secretase activity in brain regions affected by the disease. We have demonstrated that robust β-secretase activity is also detectable in platelets that contain APP and release Aβ. This review considers the current evidence for alterations in β-secretase activity, and/or alterations in BACE expression, in post-mortem brain tissue and platelets from individuals with AD.
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