Parkinson disease (PD), a prevalent neurodegenerative motor disorder, is characterized by the rather selective loss of dopaminergic neurons and the presence of ␣-synuclein-enriched Lewy body inclusions in the substantia nigra of the midbrain. Although the etiology of PD remains incompletely understood, emerging evidence suggests that dysregulated iron homeostasis may be involved. Notably, nigral dopaminergic neurons are enriched in iron, the uptake of which is facilitated by the divalent metal ion transporter DMT1. To clarify the role of iron in PD, we generated SH-SY5Y cells stably expressing DMT1 either singly or in combination with wild type or mutant ␣-synuclein. We found that DMT1 overexpression dramatically enhances Fe 2؉ uptake, which concomitantly promotes cell death. This Fe 2؉ -mediated toxicity is aggravated by the presence of mutant ␣-synuclein expression, resulting in increased oxidative stress and DNA damage. Curiously, Fe 2؉ -mediated cell death does not appear to involve apoptosis. Instead, the phenomenon seems to occur as a result of excessive autophagic activity. Accordingly, pharmacological inhibition of autophagy reverses cell death mediated by Fe 2؉ overloading. Taken together, our results suggest a role for iron in PD pathogenesis and provide a mechanism underlying Fe 2؉ -mediated cell death.Parkinson disease (PD) 3 is the most common motor neurodegenerative disorder, affecting 1-2% of the population over the age of 65. Pathologically, it is characterized by selective dopaminergic neuron loss and the presence of Lewy bodies immunoreactive for ␣-synuclein in the substantia nigra pars compacta. To date, the leading causes for the sporadic form of the disease remain unclear, although there is accumulating evidence implicating oxidative stress (1), including the finding that PD brains have increased levels of oxidative damage to DNA, proteins, and lipids (2-4). One potential player contributing to increased oxidative stress is iron, which can convert hydrogen peroxide to highly reactive hydroxyl radicals via the Fenton reaction. Indeed, increased deposition of iron was found in microglia, astrocytes, oligodendrocytes, and dopaminergic neurons of the substantia nigra pars compacta of post-mortem PD brains (5, 6). The total iron content was found to be significantly higher in the substantia nigra pars compacta of PD patients together with a corresponding increase in divalent metal transporter-1 (DMT1) transcripts in the same region (7). This suggests a close association among DMT1 expression, iron overload, and PD.Mutations in a number of genes have also been implicated in the pathogenesis of PD (8) of which the first to be discovered was ␣-synuclein. Besides the A53T, A30P, and E46K missense mutations (9 -11), duplication (12, 13) and triplication (14) of the ␣-synuclein gene have also been linked to familial forms of PD. It has been suggested that the tendency of ␣-synuclein to undergo misfolding and aggregation may underlie its involvement in Lewy body formation and hence PD (15). Given that i...

In the past, medical museums played a significant role in anatomy and pathology training. The attraction of medical museums has declined recently due to the emergence of information technology and innovative medical curricula. An innovative mobile learning platform has been developed using quick response (QR) codes for the museum specimens at the Lee Kong Chain School of Medicine, Singapore. High-quality images of the potted specimens were captured and combined into an album and a video using Adobe Acrobat Pro 9 and Windows Movie Maker, respectively. Subsequently, QR codes were generated linking to PDF documents with annotations, pathology, and clinical history concerning the specimens. Quick response codes were piloted in gastrointestinal teaching module for Year 2 medical students. Survey responses were obtained from students to verify the efficacy of QR as a learning tool. The majority of students either agreed or strongly agreed that it was easy to access the information about the specimen with QR codes (4.47 ± 0.84), while 96% of students agreed that they are able to correlate the specimen with the annotated images (4.56 ± 0.56). The majority of students (78%) agreed that QR codes are useful for their learning (4.22 ± 0.87), while 75% of students felt QR codes motivate them to visit Anatomy Resource Centre. Most of the students agreed that QR codes are useful for revision of materials (4.13 ± 1.07) and independent learning (4.38 ± 0.87). These findings suggest that QR codes are not only effective for students learning but also enhance their exploration experience with the museum specimens. Anat Sci Educ 12: 664-672.

The objective of our research is to find out if gamification increases motivation for self-directed learning (SDL) of human anatomy among year 1 medical students, and more importantly, their academic grades (n = 120). At the NUS Yong Loo Lin School of Medicine, anatomy teaching has traditionally been delivered via didactic means. To encourage more active learning, suitable games (non-digital) and the script concordance test were utilized to enhance the process. The flipped classroom approach was also introduced to further trigger active learning. In addition, the use of mobile apps (digital) was also initiated as supplements for SDL. Feedback was collected based on the previously validated PRO-SDL scale. Results from the research yielded inconclusive evidence to support enhanced motivation among our students due to gamification (P > 0.05). However, it did help to encourage active participation for a "fun learning" experience supported by numerous positive comments. More importantly, the participant's continuous assessment (CA1, CA2, and CA3) and objective specific practical exam results were better than the cohort's average (P < 0.05), suggesting that enhanced meta-cognition, and factual recall had taken place. While it is positive, there are some caveats to note with gamification, first and foremost, that it is tutor dependent. Taken together, gamification could represent a new paradigm for anatomy education, and also an opportune time to change the prevailing culture in the healthcare and education industry. Clin. Anat. 31:997-1005, 2018. © 2018 Wiley Periodicals, Inc.

Chronic and recurring pressure ulcers (PUs) create an unmet need for predictive biomarkers. In this work, we examine the panniculus carnosus, a thin cutaneous muscle, traditionally considered vestigial in humans, and ask whether the panniculus may play a role in the chronicity and reinjury of heel PUs. To determine whether humans have a panniculus muscle layer at the heel, we dissected eight cadavers. To assess the influence of the panniculus layer on PU, we performed computational simulations of supine weight bearing. Finally, we assessed panniculus regeneration in fluorescent mice. Results show a panniculus layer present in all cadavers examined. Simulations show a thin layer of panniculus muscle causes a dramatic decrease in the volume of soft tissue experiencing high strain and stress, compared to a heel without a panniculus. Importantly, in the mouse model, the panniculus fails to regenerate after PU, even when other cutaneous layers had fully regenerated. Our work shows that the panniculus is able to redistribute load around the heel bone, which might allow it to prevent PUs. Moreover, it is highly susceptible to incomplete regeneration after PU. Poor panniculus regeneration after PU might be a predictive anatomical biomarker for recurrence, and this biomarker should be evaluated prospectively in future clinical trials.

Background Human pressure injuries (PI) exhibit delayed healing and are classified as chronic wounds, and muscle damage increases the chronicity and severity of PIs. Pressure or load redistribution is typically the gold standard for preventing PIs in bedridden patients or those with limited mobility. The panniculus carnosus (PC) is a thin muscle in the cutaneous layer. Although evidence of the PC layer in multiple anatomical locations such as the heel has been reported, with high inter‐individual variability, the PC is traditionally considered to be vestigial in humans. In this work, we investigate the role of the PC layer in biomechanics and load distribution, and ask how the PC regenerates after a pressure‐induced injury. Methods To examine the biomechanical function of the PC, a finite element analysis was performed on a three‐dimensional model of the human heel, comparing the change in soft tissue deformation during supine weight‐bearing, with and without the PC. To assess PC regeneration, a mouse with inducible confetti‐colored fluorescent satellite cells (muscle stem cells) was developed by crossing the Brainbow2.1 mouse with a conditional Pax7CreER mouse. The resulting mouse, upon tamoxifen induction, provides fluorescent colors for lineage tracing of muscle regeneration in vivo. Muscle PIs were created in these mice by applying a pair of 12mm magnets to the dorsal skinfold and PC muscle, in two intervals of 12 hours. Results In computational simulations of heel tissue, we find extensive overall displacement of soft tissues around the bony prominence during weight bearing, which was greatly decreased in the presence of the PC layer. Additionally, the presence of PC decreased the volume of tissue experiencing high strain and stress. When the PCs of mice were injured by pressure, tissue histology and fluorescent tracing of endogenous stem cells showed that the PC failed to regenerate across the distances necessary for this two‐dimensional sheet‐like structure. Even at 90 days following injury, a hole remained in the PC, while the other tissue layers regenerated successfully. Furthermore, multiple split and deformed myofibers were observed in the newly regenerated muscle at the wound edge. Conclusions Our work shows that the PC layer is sufficient to redistribute load around the posterior of the heel bone, reducing the volume of displaced tissue and the volume of soft tissue experiencing high strain and stress. Moreover, upon pressure injury, the PC layer is highly susceptible to poor regeneration and abnormalities in the geometry of the resulting fibers. Split or deformed fibers are weaker and more susceptible to repeated injury and this could be an underlying pathology of recurrent human PIs. We conclude that the PC might play an important protective function in pressure redistribution and that the PC regenerates poorly after PI. This absence or deformation of PC could be a potential risk factor for PI recurrence.